KR101053731B1 - Method for preparing dissolution time-controlled enteric cleaner composition - Google Patents

Abstract

[Name] Method for preparing dissolution time-controlled enteric cleaner composition

[Composition] 100 g (I) of powder mixed so that the ratio of monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) was 32.0 g: 68.0 g by weight, and the ratio of shellac and PG was weight ratio. Stearate-based lubricating agent 0.5, such as material (II) mixed so as to be 40.0 g: 60.0 g to 60.0 g: 40.0 g, water-soluble binder material 10.0 g (III), magnesium stearate, etc. After preparing ~ 2.0g (IV), the materials of (I), (II), (III) and (IV) were added to the stirrer and mixed at room temperature for 30 minutes or more, and then the diameter of 2-10 mm After making the solid ring, the shellac and the PG ratio was 95.0g: 5.0g in weight ratio, and the mixed base resin was dissolved in ethanol so as to have a solid concentration of 20-40 wt%. It is characterized in that it is completed by coating and drying.

[A task to solve]

Unlike conventional enteric cleaners, they are dissolved from the small intestine rather than from the stomach, which not only minimize side effects in the stomach, but also facilitate oral administration and reduce the dosage of the enteric cleaner and are completely soluble in water. Invented a method for preparing a bowel cleanser composition to ensure that there is no residue on the wall of the intestine

 Enteric detergent, dissolution time, monosodium phosphate, disodium phosphate, shellac, PG

Description

Method for preparing dissolution time-controlled enteric cleaner composition {The Product Method for Intestines Detergent Material}

The present invention relates to a method for preparing a dissolution time controlled enteric cleaner composition.

That is, the composition of sodium phosphate used in the washing section for colonoscopy, and as to this ease of use for oral relates to a process for producing a ring form, and more particularly, a phosphate sodium (NaH ₂ PO ₄ mixed at a proper ratio ) And edible sodium phosphate (Na ₂ HPO ₄ ) powder mixed with edible natural adhesive to make it into granules to make it easy to be used for oral use. The ring is to be dissolved from the small intestine rather than the stomach, and the composition of the present invention is made in the form of a ring and then coated with a coating material described below or a coating material is made into capsules and the composition of the present invention is inserted into a capsule into a capsule.

Therefore, unlike conventional enteric cleaners, the present invention relates to a method for preparing an oral enteric cleaner composition which minimizes gastrointestinal rejection and effectively washes the intestine (small intestine and large intestine) by a relatively small amount of oral dosage. .

Soline-liquid oral [Korea Pharma Co., Ltd.], which is generally marketed as an oral enteric cleanser, is a mixture of monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) in water. It is formulated by mixing a small amount of fragrance in the dissolved solution. Sodium phosphate dissolves in water to give acidity, and disodium phosphate dissolves in water to give basicity. It is made of acidity liquid. Phosphate solution causes osmotic phenomenon in the intestine, so that a large amount of water is absorbed from the intestine, thereby facilitating intestinal washing.

However, the biggest disadvantage of such a liquid oral cleaning agent is the nasty taste and smell that the patient feels in the mouth. In particular, a child or woman with a weak stomach is often feeling disgusting or vomiting to the extent that it is almost impossible to administer, and thus, it is often impossible to perform proper colonoscopy. Another drawback is that liquid preparations begin pharmacologically in the stomach immediately after injection, so people with weak stomachs often complain of side effects such as bloating or pain in addition to nausea and nausea.

In order to minimize these side effects, recently, in the United States, liquid enteric detergents are made in tablet form and sold as products, which are also used in hospitals. This is done by combining binder and other processing such as microcrystalline cellulose (hereinafter referred to as MC) in the mixture of monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ). It is prepared in the form of a tablet weighing about 1.7g per dog using the preparation.

Currently, it is marketed in the US under the name of Visicol ™ or Osmoprep ™, and once colonoscopy is administered 20 days before the test, and 12 times again on the day of the test (eg 30 minutes to 1 hour) Should be taken at regular intervals. On the other hand, the current tablet-type enteric cleaner made in this way has an advantage that it is easy to store or administer compared to liquid enteric cleaner, but still has a decisive disadvantage that it works by melting from the stomach, and in the case of Koreans, the shape of the tablet for oral administration The problem is that the size is relatively large. In addition, the above-mentioned MC used as a binder is a crystalline substance, which is completely dissolved in the body within a short time and is not removed, but may remain on the wall of the intestine and cause misdiagnosis during the inspection (see US P 20050129781).

Therefore, while overcoming the above disadvantages, the oral administration is easy, the above-described side effects are minimized, and the development of a new type of enteric cleaner which can effectively clean the intestine as a relatively small amount of enteric detergent is urgently required.

Therefore, the present invention is not only to minimize the side effects in the stomach because it is easy to oral administration for intestinal washing for colonoscopy and dissolve from the small intestine, as well as to reduce the dosage of the intestinal cleansing agent, completely soluble in water The problem is to provide a method for preparing an enteric cleanser composition which minimizes misdiagnosis when observing colonoscopy so that there is no residue on the walls of the intestine.

The present invention is configured as follows.

[First Composition Example]

100 g (I) of powder mixed so that the ratio of monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) was 32.0 g: 68.0 g by weight, and the ratio of shellac and PG was 40.0 g by weight : 60.0g ~ 60.0g: Material (II) mixed to be 40.0g, 10.0g (III) of water-soluble binder material, 0.5-2.0g (Magnesium Stearate) which is a stearate food lubricant IV) were prepared, and the materials of (I), (II), (III) and (IV) were added to the stirrer, mixed at room temperature for 30 minutes or more, and then a solid ring having a diameter of 2 to 10 mm was made. Subsequently, the base resin was coated and dried at room temperature using a coating agent prepared by dissolving the mixed base resin in a weight ratio of 95.0 g: 5.0 g in a weight ratio of ethanol to a solid concentration of 20-40 wt%, followed by drying. It is characterized in that completed by.

Second Composition Example

100 g (I) of powder mixed so that the ratio of monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) was 32.0 g: 68.0 g by weight, and the ratio of shellac and PG was 40.0 g by weight : 60.0g ~ 60.0g: Material (II) mixed to be 40.0g, 10.0g (III) of water-soluble binder material, 0.5-2.0g (Magnesium Stearate) which is a stearate food lubricant After preparing IV), the materials of (I), (II), (III) and (IV) were added to a stirrer and mixed at room temperature for at least 30 minutes, and then a solid ring having a diameter of 2 mm or less was made. The solid ring was mixed into a capsule of a normal size using a coating made by dissolving the base resin mixed with shellac and PG in a weight ratio of 95.0 g: 5.0 g in ethanol so as to have a solid concentration of 20-40% by weight. It is characterized in that the filling is completed.

In the first and second compositions described above, a non-reactive edible plasticizer and an edible lubricant are added to the base resin of the coating agent, and the lemon or apple flavor used as an edible flavoring agent is added in a weight ratio to 100 g of the base resin. 0.01 to 0.1 g and an edible lubricant are introduced in the range of 1.0 to 5.0 g in a weight ratio to 100 g of the base resin. In addition, in the first composition example, by dissolving the coating agent concentration to be coated on the solid ring different from each other characterized in that the dissolution time can be different for each coating agent concentration, in the second composition example, the solid ring is accommodated By dissolving the concentration of the coating agent which is the material of the capsule to be different from each other characterized in that the dissolution time can be different for each capsule.

In addition, the present invention has been made to solve the above-mentioned conventional problems, by introducing several technical methods generally developed in the current pharmaceutical manufacturing process can be prepared in the form of solid particles in the form of a ring easier to oral administration. Control the composition ratio of the cleaning agent and the binder so that the actual action of the administered detergent occurs after the small intestine rather than the stomach, and the binder material is completely dissolved in water to assist intestinal washing by volume expansion. It provides a new intestinal cleanser in the form of a solid ring or a regular sized tablet that is completely discharged without intestinal residues to help minimize the physical side effects of the subject and facilitate the colonoscopy. In addition, the material used in the binder and coating agent used in the present invention is a water-soluble organic material, but because it is not digested by the digestive action of the intestine does not cause gas in the intestine due to digestion, as in general food.

In addition, the enteric cleansing agent of the present invention relates to a sodium phosphate composition generally used for enteral cleaning for colonoscopy, and to a method of preparing the same in the form of a solid ring or tablet so as to be easily used for oral use, and more particularly, titration. The monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) powders mixed in proportion are encapsulated with an edible natural resin, or mixed with a water-soluble natural resin binder to form a granule orally. It is easy to add to the composition, and the composition is used to vary the concentration of the coating so that it dissolves from the intestines, not the stomach. Minimizing and relatively small doses of oral dosing can effectively There is one aspect to.

On the other hand, the present invention is most suitable for the oral administration habits or methods of the Korean by using a water-soluble binder and coating agent edible in powdered sodium monophosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) powder in an appropriate ratio. It is manufactured in the form of capsules or coated solid rings to control the size, shape and dissolution time. As the water-soluble binder used in the present invention, polyvinyl alcohol (PVA), polyethylene glycol (PEG), microcrystalline cellulose (MC) or shellac (natural adhesive) shellac is appropriately plasticized with a propylene glycol (PG) plasticizer. For example, the mixed resin. Among them, a mixture resin of shellac and propylene glycol has an advantage of being used in combination as a binder of a powder or a coating agent of a manufactured solid ring according to a mixed composition.

The present invention uses the above binder to form monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) powder in the form of a capsule in a desired size and shape, or in the form of a solid ring, without objection. By encapsulation to facilitate oral administration and control of dissolution time or by coating the outside of the pill, it is dissolved after a certain period of time after oral administration so that the cleaning agent is actually washed after the small intestine necessary for colonoscopy. .

Edible natural product resins such as shellac are treated to have a subtle scent, such as lemon or apple flavors, to minimize rejection when administered orally, and are compatible with edible plasticizers such as propylene glycol over the entire concentration range. Therefore, by adjusting the composition ratio, there is an advantage that can be used simultaneously as a binder and a coating agent, so by adjusting the coating thickness can be adjusted so that the administered detergent is dissolved from the intestine, not the stomach, even if administered at a certain time difference. In addition, the dissolved resin absorbs a large amount of water in the process of dissolving in water and dissolves, and has a function of assisting intestinal washing by the increase effect without generating by-products such as gas because it is irrelevant to the digestion of the intestine.

Hereinafter, the manufacturing method of the present invention will be described in detail.

[Composition of Mixed Sodium Phosphate (NaH ₂ PO ₄ ) and Disodium Phosphate (Na ₂ HPO ₄ )]

Monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) used in the present invention are basic and acidic solutions when dissolved in water, respectively. It is necessary to adjust to this.
Therefore, the composition of monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) powder was dissolved in water by mixing so that the ratio of monosodium phosphate and disodium phosphate was 32.0g: 68.0g in weight ratio. When you can make a neutral solution.
Such monosodium phosphate and disodium phosphate mixed materials are generally used as long cleaning materials for colonoscopy as described above, and thus can be used as they are in the present invention. However, the mixing ratio of monosodium phosphate and disodium phosphate in the present invention is used by mixing in powder form to adjust the weight ratio to be a neutral aqueous solution in the vicinity of PH 7.0 dissolved in water.

[Binding material]

It is a binder compound used to make monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) mixed powder into solid particles in a cyclic form. As a binder material, the physical and chemical properties required for the present invention are harmless to the human body and should be water-soluble so that it can be completely dissolved in water, and is not digested or absorbed by the intestine (gastrointestinal, small intestine, large intestine) and thus enters the intestine. Do not generate any by-products such as gases in the furnace.
In general, the water-soluble compounds having such characteristics are polyvinyl alcohol (PVA), microcrystalline cellulose (MC), and polyethylene glycol (PEG) water-soluble high molecular compounds. Among them, MC used as a binder in Visicol ^® and the like is a powder in the market. 14.0 to 16.0 g is used as a weight ratio per 100 g of the mixed powder of monosodium phosphate and disodium phosphate by using a purified product in the form, and 0.16 to 2.0 g of magnesium stearate and silicon dioxide ( Silicone Dioxide) is used by adding 0.5 to 0.7 g of suspension. The added processing aid serves as viscosity control, lubrication and dispersant for workability in the production of solid rings.

However, since MC is a physically small form of crystalline substance, it may remain in the intestine without completely dissolving in the digestive solution during the passage of the intestine. Due to this phenomenon, in order to perform an accurate colonoscopy, it is necessary to perform additional work to remove the MC residue in the intestine, which results in a delay in the examination time and increased patient discomfort. It was solved.

PEG can also be used as a water-soluble binder material that is very easily soluble in water. When the molecular weight is about 1,000 or more, it is a solid form at room temperature. Thus, PEG is used as a binder of the mixed powder of monosodium phosphate and disodium phosphate. It can be made in the form, which is also shown in the aforementioned patent application 2005-0129781.

In this case, however, the tablet's inherent physical properties are waxy, and the tablets begin to dissolve in the mouth or stomach immediately after oral administration. The discomfort of the patient due to side effects in the stomach after rejection or oral administration to oral administration is not eliminated, the present invention solved this problem.

On the other hand, the shellac natural polymer compound as used in the present invention is a natural adhesive binder material for food coating, which is harmless to the human body and used by being extracted and purified from the secretion of natural Lac insects. (CAS 9000-59-3).
Currently, it is used as a coating film for foods such as chocolate, candy, and xylitol gum in general, and is also used for pharmaceuticals. It is a natural resin of shellac varnish made in solution in alcohol, and is widely used for coating film formation as a substitute for lacquer.In the case of pharmaceutical use, it is possible to control the absorption rate of medicinal components by adjusting the coating thickness. will be.
Shellac itself is a natural polymer resin that does not easily dissolve in water at room temperature because of its melting temperature of about 75 ℃, but at a temperature of about 80 ℃ in the weight ratio of about 10.0g sodium hydrogen hydrogen (NaHCO ₃ ) and 30.0 to 40.0 by weight ratio Melting about g of shellac can produce a binder material that is very easy to use.
In addition, shellac is compatible with water-soluble alcohols such as propylene glycol (PG, CH ₃ CHOHCH ₂ OH) over a full range of concentrations, eliminating the need for water by controlling the composition ratio in binder materials made from a mixture of shellac and PG. It can also be used as a binder material.
In the case of a binder material using water, since the mixed powder of monosodium phosphate and disodium phosphate itself is water-soluble, it may be difficult to prepare a solid ring. In the present invention, an anhydrous binder material using a mixture of shellac and PG is used as an example. Suggest. That is, by mixing 100.0 to 200.0g of shellac at a weight ratio of 100g of PG at a temperature of about 95 ° C, and then melting it at room temperature, a binder material that is easy to use can be made.

[Coating Materials]

Tablets such as Visicol ^® made of tablets using binder materials such as MC and PEG are relatively easy to administer orally, but still have an unpleasant odor and taste and relatively large tablets compared to Asians. It does not overcome the disadvantages of side effects of patients due to the melting from the pulp and mouth.
The present invention proposes a method of making or encapsulating a solid ring to improve these points. As a coating material for coating used in the present invention, the necessary feature is that the drug is dissolved in water (specifically, the intestinal liquid constituting the gastrointestinal digestive fluid) until a certain time passes from the stomach to the small intestine after the drug is orally administered. It must have a delayed dissolution characteristic that dissolves after transfer to the small intestine and allows the washing of the drug to begin thereafter.
Of course, it should be harmless to the human body and should not have any side effects of digestive absorption or gas generation by the human digestive fluid. As a drug using an encapsulating material or a coating material having a delayed dissolution characteristic having such characteristics, it can be found in a contact 600, which is commercially available as a cold medicine, but as proposed in the present invention, such as an encapsulated enteric cleaner or a mixture of shellac and PG. Enteric colon cleaners coated with a functional coating film made of a water-soluble resin are not found.

On the other hand, examples of the coating material for coating proposed and used in the present invention include a mixture of shellac & PG used as a binder and a coating material in the production of a solid ring of the mixed powder of monosodium phosphate and disodium phosphate.
The biggest advantage of the resin material such as the mixture of shellac & PG proposed in the present invention is that the viscosity or the time to dissolve in water can be adjusted as desired depending on the composition ratio of PG. As another advantage, when used as a coating agent it is possible to control the melting time in water by adjusting the thickness of the film.
The completely dried shellac coating without moisture exhibits very brittle properties, but when a plasticizer such as PG is incorporated or there is a little moisture, a soft coating is formed. This property prevents the occurrence of defects due to breakage of the coating during the process of transporting the coated pills.
Therefore, the mixture of shellac & PG can be used as a binder material required for the production of a solid ring having a controlled dissolution time of a mixed powder of monosodium phosphate and disodium phosphate according to the composition ratio, and can also be used as a coating material for ring grains. The additional economic burden of having to select and purchase and test coating materials separately can be avoided.
Spices such as edible lemon and the like in the shellac & PG mixture can be greatly mixed with about 0.1 g in a weight ratio per 100 g of the shellac & PG mixture, thereby greatly reducing the rejection of oral administration due to the pleasant odor.

[Manufacture and Coating of Solid Rings]

The method for preparing a dissolution time-controlled enteric cleaner solid ring can be applied mutatis mutandis to the methods used for preparing a general pharmaceutical product. The manufacturing process of the solid granular ring can be applied mutatis mutandis to commercially available methods of making Jeongrohwan, and the encapsulation process or coating film treatment can use the encapsulation manufacturing process and coating process of contact 600 as it is. Also select the normal size.

Looking at a specific embodiment of the solid ring production of the present invention as described above are as follows.

Example 1

To 100 g of powder mixed so that the ratio of monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) is 32.0 g: 68.0 g by weight, the ratio of shellac and PG is 60.0 g: 40.0 g by weight 10.0 g of the mixed binder material and 1.0 g of magnesium stearate are mixed to facilitate oral administration according to the manufacturing process used in the manufacture of general solid granules (preferably 2-10 mm in diameter). About 5mm size) After making the granules of the size of the cleanser, the base resin mixed so that the ratio of shellac and PG is 95.0g: 5.0g by weight ratio is ethanol (Ethanol, C ₂ H ₅ OH) A dissolution time-controlled enteric cleaner solid ring was prepared by coating at room temperature using a coating agent (coating agent-01) to be dissolved in).

The ring grains thus prepared were put in lukewarm water at 36 ° C. and slowly stirred to measure the time at which the pellets dissolved in water and began to disperse. Table 1 shows the mixing ratio of the detergent electrolyte, the mixed binder material of shellac and PG, the mixing ratio of the coating agent, and the composition ratio in the total mixture thereof, expressed in weight percent. And in Table 2, the composition ratio with respect to the mixed coating agent of water-soluble shellac & PG for the coating process of the solid ring made with the composition ratio in Table 1 was shown.

Table 1. Examples of Compositions and Composition Ratios for the Preparation of Solid Ring Granules

Table 2. Examples of Compositions and Composition Ratios for Coating Treatment of Solid Rings with Total Composition Ratios in Table 1

[Example 2]

Dissolution time control type by making a long-time wash solid granules prepared under the same conditions as in Example 1 and then coating at room temperature with the coating agent-02 prepared so that the concentration of shellac & PG prepared in advance by the above method to 30% by weight An enteric cleaner solid ring was prepared and the time to start to dissolve in water was measured as in Example 1.

Example 3

Dissolution time control type by coating the film at room temperature using the coating agent-03 prepared to prepare the concentration of shellac & PG prepared in the same manner as in Example 1 and then to the concentration of shellac & PG prepared in the above manner by 40% by weight An enteric cleaner solid ring was prepared and the time to start to dissolve in water was measured as in Example 1.

Comparative Example 1

The tablet-type enteric cleaner which is commercially available in the United States, etc. was purchased and the time to start to dissolve in water under the same conditions as in Example 1 was measured. Looking at the experimental results obtained in Examples 1 to 3 and Comparative Example 1 is as shown in Table 1.

[Table 1] Comparison of Water Solubility of Coating Dissolution Time Controlled Solid Ring Cleaner

As described above, the tablet which is not coated starts to melt immediately after contacting with water, and after about 30 minutes, almost half or more of the tablet melts, whereas the dissolution time controlled enteric cleaner (solid ring) according to the present invention is It can be seen that the melting time varies depending on the coating treatment method. That is, the time to dissolve in water can be adjusted by adjusting the concentration of the coating or the number of coatings, which can be selected according to need.

For example, the coating agent-01 has a coating thickness of about 10 μm in one coating. Experimental picture 1 (Experimental picture 2, Experimental picture 3 are also presented for reference in the following), which is presented as a reference for better understanding of the present invention, shows the tablet shape before and after coating.
Coated tablets have a glossy, smooth appearance. Photo 2 also shows the modified tablet shape after 30 minutes in water at 36 ° C. using a tablet coated with coating agent-01 0, 1, 2, 3 and 4 times. If you look at this, as the number of coatings increases, the melting time in water can be observed clearly. Photograph 3 shows the time taken for coating 3 to be coated and uncoated to about the same amount. That is, in the case of coating, it can be seen that almost two hours must be dissolved to the same extent as uncoated.

This result means that the melting time can be controlled by the concentration of the coating or the number of coating. Therefore, it can be seen that the dissolution time controlled enteric cleaner according to the present invention is relatively superior in oral administration method and effect in comparison with the conventional liquid enteric cleaner or tablet type enteric cleaner.
In addition, it is a small ring-shaped solid granule with a pleasant fragrance, so it is very easy for Koreans to resist oral administration, and it is very easy to administer it. It can be seen that there is an advantage to prevent discomfort such as nausea, vomiting, gas development by minimizing gastrointestinal rejection by dissolving and working.

Intestinal cleanser composition according to the present invention as described above, because it is easy to oral administration for intestinal endoscopy for colonoscopy and dissolves from the small intestine can not only reduce the dosage of the intestinal cleanser, but also minimize side effects. In addition, it is completely dissolved in water and discharged so that there is no residue on the wall of the intestine, which minimizes the misdiagnosis when observing colonoscopy, and the fragrance can minimize the objection to oral administration of patients. By using a harmless natural resin, the solid ring is coated (coated) to control the dissolution time so that the enteric detergent can dissolve only after gastrointestinal tract, enabling more effective cleaning and safety through patients' psychological stability without rejection or side effects. And perform an accurate endoscopy This can be useful.

Claims (5)

100 g (I) of powder mixed so that the ratio of monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) was 32.0 g: 68.0 g by weight, and the ratio of shellac and PG was 40.0 g by weight : 60.0g ~ 60.0g: Material (II) mixed to be 40.0g, 10.0g (III) of water-soluble binder material, 0.5-2.0g (Magnesium Stearate) which is a stearate food lubricant IV) were prepared, and the materials of (I), (II), (III) and (IV) were added to the stirrer, mixed at room temperature for 30 minutes or more, and then a solid ring having a diameter of 2 to 10 mm was made. Subsequently, the base resin was coated and dried at room temperature using a coating agent prepared by dissolving the mixed base resin in a weight ratio of 95.0 g: 5.0 g in a weight ratio of ethanol to a solid concentration of 20-40 wt%, followed by drying. Preparation of dissolution time-controlled enteric cleaner composition, characterized in that completed by Law. 100 g (I) of powder mixed so that the ratio of monosodium phosphate (NaH ₂ PO ₄ ) and disodium phosphate (Na ₂ HPO ₄ ) was 32.0 g: 68.0 g by weight, and the ratio of shellac and PG was 40.0 g by weight : 60.0g ~ 60.0g: Material (II) mixed to be 40.0g, 10.0g (III) of water-soluble binder material, 0.5-2.0g (Magnesium Stearate) which is a stearate food lubricant After preparing IV), the materials of (I), (II), (III) and (IV) were added to a stirrer and mixed at room temperature for at least 30 minutes, and then a solid ring having a diameter of 2 mm or less was made. The solid ring was mixed into a capsule of a normal size using a coating made by dissolving the base resin mixed with shellac and PG in a weight ratio of 95.0 g: 5.0 g in ethanol so as to have a solid concentration of 20-40% by weight. Dissolving time adjustable enteric cleaner composition, characterized in that completed by filling The method of manufacture. The non-reactive edible plasticizer and the edible lubricant are added to the base resin of the coating agent, and lemon or apple flavor used as an edible flavoring agent is added in a weight ratio of 100 g of the base resin. ~ 0.1 g, food grade lubricant is added in the range of 1.0 to 5.0 g in a weight ratio to 100 g of the base resin, the method for producing a dissolution time-controlling type long-cleaning composition. The method of claim 1, wherein the dissolution time of the coating composition is different by coating the concentration of the coating agent coated on the solid ring to be different from each other. The method of claim 2, wherein the dissolution time is adjusted for each capsule by different concentrations of the coating agent, which is a material of the capsule containing the solid ring, to allow different dissolution times. .