JPH10236960A - Composition containing antacid agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition containing an antacid agent, not only excellent in safety but also excellent in immediate effectiveness, high antacid function and stomach mucous membrane protecting effect by an adhesion effect to the stomach mucous membrane by selecting a particle size distribution of a conventionally used antacid and setting a specific blended composition. SOLUTION: This composition containing an antacid agent is obtained by blending a magnesium oxide of which >=80wt.% of the total has 75-300μm particle diameter, with a synthetic hydrotalcite of which >=85wt.% of the total has 75-300μm particle diameter so as to make a weight ratio of the magnesium oxide to the synthetic hydrotalcite as (8:1)-(1:8).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an antacid-containing composition, and more particularly, to a method of adhering to a peptic ulcer for a long time and coating the surface of the gastric mucosa to enhance the therapeutic effect on the ulcer lesion. The present invention relates to an antacid containing composition.

[0002]

BACKGROUND OF THE INVENTION Conventionally, many antacids have been used to treat peptic ulcers, gastritis, hyperacidity, heartburn, and gastric discomfort. Among them, synthetic hydrotalcite, dry aluminum hydroxide gel, aluminum hydroxide-sodium bicarbonate co-precipitate, synthetic aluminum silicate, aluminum glycinate, aluminum metasilicate for the purpose of protecting the lesion of peptic ulcer from gastric acid Although aluminum-containing antacids such as magnesium acid are used, these conventional aluminum-based antacids alone have a short time to adhere to the lesion and a short period of time after they are taken, and the lesion has a short duration. The function of protecting the mucous membrane is not yet sufficient.

[0003] That is, the gastric mucosa-adhering action of an aluminum antacid is based on the fact that when the pH in the stomach is 3 to 5, dissolved aluminum becomes basic aluminum chloride and binds to acidic glycoprotein on the gastric mucosal layer, It is thought to protect the mucous membrane. Therefore, if the taken antacid maintains the intragastric pH at 3 to 5 for a long time, it exerts an excellent gastric mucosal protective effect and can be an effective drug for the gastric ulcer lesion. However, when aluminum glycinate, synthetic hydrotalcite, dry aluminum hydroxide, or the like is taken alone, the dose must be increased to maintain the gastric pH at 3 to 5 for a long time. In addition to being painful for the patient, there are also concerns about side effects such as diarrhea. In addition, these antacids do not have sufficient adhesion of aluminum ions to the gastric mucosa, and have a weak gastric mucosal protective effect. In the case of magnesium silicate or synthetic magnesium silicate, the initial dissolution rate is rather slow, and the gastric pH is 3
It has been pointed out that the starting speed is significantly slow.

[0004] The present invention has been made in view of the above circumstances, and by improving the buffering capacity of the antacid to adjust the gastric pH to 3 to 5, the dose is drastically reduced to improve the ingestibility. An object of the present invention is to provide an antacid-containing composition that not only has high safety but also has a significantly increased adhesion of aluminum ions to gastric ulcer lesions, and has an excellent gastric mucosal protective effect. .

[0005]

Means for Solving the Problems and Embodiments of the Invention The present inventor has conducted intensive studies in order to solve the above problems, and as a result,
By using magnesium oxide having a specific particle size distribution and synthetic hydrotalcite at a predetermined ratio as an antacid, the gastric pH can be quickly maintained at pH 3 to 5 and maintained for a long time. As a result, the present inventors have found that the dosage of an antacid can be greatly reduced, and have accomplished the present invention.

That is, according to the present invention, a weight ratio of magnesium oxide having a particle size of 75 to 300 μm at least 80% by weight and synthetic hydrotalcite having a particle size of 75 to 300 μm at least 85% by weight is determined. Provided is an antacid-containing composition, which is blended so that magnesium oxide: synthetic hydrotalcite = 8: 1 to 1: 8.

Hereinafter, the present invention will be described in more detail. The antacid-containing composition of the present invention contains magnesium oxide and synthetic hydrotalcite. Here, the mixing ratio of magnesium oxide and synthetic hydrotalcite is 0.125 to 8 parts by weight, preferably 0.3 to 6.0 parts by weight of synthetic hydrotalcite per 1 part by weight of magnesium oxide. Preferably it is 0.4 to 4.0 parts by weight. If the compounding ratio of the synthetic hydrotalcite is too low, the amount of adhesion to the gastric mucosa is small and the mucosal protective effect is not sufficiently exhibited, and there is a concern that the pH of gastric juice may increase to 6 or more.
On the other hand, if the blending ratio of the synthetic hydrotalcite is too high, the time required for the intragastric pH to reach pH 3 becomes longer and the amount of the dissolved hydrotalcite dissolved becomes smaller, so that efficient adhesion of aluminum ions to the mucosa is obtained. Can not do.

The amount of the above-mentioned antacid in the whole antacid-containing composition of the present invention is not particularly limited as long as the mixing ratio of magnesium oxide and synthetic hydrotalcite is within the above range. It is suitable that the total amount of the magnesium oxide and the synthetic hydrotalcite is 20 to 80% by weight, preferably 25 to 75% by weight, more preferably 30 to 70% by weight of the whole antacid-containing composition. If the amount of the antacid is too large, not only the formulation becomes difficult, but also the long-term storage stability of the antacid may not be obtained.If the amount is too small, it is difficult to obtain a sufficient antacid effect. It may be.

Further, in the antacid-containing composition of the present invention, 80% by weight or more, preferably 83% by weight or more, more preferably 88% by weight or more of the magnesium oxide has a particle size of 75 to 300 μm, preferably 75-180 μm,
More preferably, those having a range of 106 to 180 μm are used. In addition, the whole magnesium oxide (100%)
May be within the above range. If there are too many particles having too large a particle size, the dissolution rate of magnesium oxide will be slow, and the pH in the stomach cannot be stably maintained at 3 to 5. On the other hand, if there are too many particles having too small a particle size, the proportion of magnesium oxide that rapidly dissolves becomes too large, and the pH in the stomach becomes 6 or more, which may adversely affect the stomach's physiological functions. .

[0010] The antacid-containing composition of the present invention may contain, as the synthetic hydrotalcite, 85% by weight or more, preferably 87% by weight or more, more preferably 90% by weight or more, having a particle size of 75 to 300 µm. Preferably 75-180μ
m, more preferably in the range of 106 to 180 μm. In addition, the whole synthetic hydrotalcite (1
00%) may be within the above range. If there are too many particles having too large a particle size, the dissolution rate of the synthetic hydrotalcite becomes too slow, and sufficient adhesion of aluminum ions to the gastric mucosa cannot be obtained. On the other hand, if there are too many particles having too small a particle size, the dissolution rate of the synthetic hydrotalcite becomes too fast, and it becomes difficult to maintain the gastric pH at 3 to 5.

[0011] The antacid-containing composition of the present invention, by means of the above constitution, quickly adjusts the intragastric pH to pH 3 to 5,
The area is maintained for a long time. Here, the buffering time of the antacid is not particularly limited, but the time required to reach the inside of the stomach within the above-mentioned pH range is preferably 5 minutes or less, particularly preferably 3 minutes or less, and the time to maintain the pH range. Is preferably 20 minutes or more, particularly about 22 to 28 minutes.

The antacid composition containing the antacid of the present invention may further contain, if necessary, various medicinal ingredients other than the above antacid, as long as the effects of the present invention are not hindered. Not only human medicines, but also animal medicines may be blended, but in consideration of the intended use of the antacid-containing composition of the present invention, for example, digestive agents, stomachic agents, peptic ulcer agents, intestinal agents and the like Are suitably blended. Specifically, as a digestive agent, starch digestive enzymes such as amylase, diastase and putialine, protein digestive enzymes such as trypsin, pepsin, papain, fat digestive enzymes such as lipase, ursodesoxycholic acid, bile powder, dehydrocholic acid Etc., as a gastric medicine, glutamate hydrochloride, betaine hydrochloride, l-menthol, carnitine chloride, dried yeast, etc.
As a peptic ulcer agent, L-glutamic acid, aldioxa, sodium azulene sulfonate, methyl methionine sulfonium chloride, dimethyl polysiloxane, etc.
Examples of the intestinal preparation include live intestinal bacteria components and the like.

The amounts of these medicinal components can be appropriately selected according to the kind and the like, but are usually about 0.001 to 50% by weight, preferably 0.01 to 40% by weight, based on the whole composition. % By weight, more preferably 0.1 to 3
It is preferable that the content be about 5% by weight.

The dosage form of the antacid-containing composition of the present invention is not particularly limited, and examples thereof include tablets, granules, powders,
Used in various dosage forms such as solid preparations such as capsules, syrups in which magnesium oxide and synthetic hydrotalcite are dispersed and suspended in powder, granules, powders and colloids, and dispersants, etc. Although each can be prepared by a conventional method, in any case, the magnesium oxide and the synthetic hydrotalcite used in the preparation need to have the above particle size distribution, and are usually in the form of powder, particularly Used in powder form. Among the various dosage forms, those in which the magnesium oxide and the synthetic hydrotalcite are in the form of powder, particularly powder, in the preparation are desirable.

In preparing the antacid-containing composition of the present invention into the above-mentioned various dosage forms, various additives other than the above-mentioned components may be added, if necessary, unless the effects of the present invention are prevented. Can be, for example, when prepared as a solid preparation,
Excipients such as lactose, starch, corn starch, sucrose, mannitol, crystalline cellulose (for example, Avicel: registered trademark, manufactured by Asahi Kasei Kogyo Co., Ltd.), hydroxypropyl cellulose, carboxymethyl cellulose, gelatin,
Binders such as sodium carboxymethylcellulose and gum arabic, calcium carboxymethylcellulose,
Disintegrators such as polyvinylpyrrolidone and its crosslinked product, nonionic surfactants such as sucrose fatty acid ester and polyoxysorbitan fatty acid ester, calcium stearate,
Magnesium stearate, dimethylpolysiloxane,
Lubricants such as talc, polyethylene glycol, hardened oil and the like can be blended, and among these, excipients and binders are widely used, and disintegrants are often added.

If necessary, a coating or sugar coating may be applied. Examples of the coating agent include hydroxypropylcellulose, hydroxypropylmethylcellulose, Eudragg, polyvinylpyrrolidone, polyethylene glycol, shellac, methylcellulose, and the like.
Ethyl cellulose, cellulose acetate phthalate, hydroxypropylcellulose phthalate and the like are used. In the case of sugar coating, sucrose, gum arabic, calcium carbonate, talc, gelatin and the like are used as the main components of sugar coating.

When prepared as a liquid preparation as described above, for example, purified water, ethanol, glycerin, sucrose, propylene glycol, polyethylene glycol,
Excipients such as polyoxyethylene sorbitan fatty acid ester, aluminum metahydroxide, agar, and tragacanth gum can be blended within a range that does not impair the effects of the present invention. Solubilizers, buffers, preservatives, fragrances, coloring agents, flavoring agents, and the like can be added as long as the effects of the present invention are not impaired.

The addition amount of the above additives is appropriately selected within a range not to impair the effects of the present invention, but is usually about 10 to 70% by weight, preferably about 15 to 65% by weight, based on the whole composition. More preferably, it is preferably about 20 to 60% by weight.

The antacid-containing composition of the present invention can be used not only as a human drug but also as an animal drug, and has both high antacidity, adhesion to gastric mucosa and rapid action.
It works effectively as an antacid to relieve symptoms such as hyperacidity, gastric discomfort, heartburn, and stomach pain.It can also be used in combination with other medicinal ingredients such as digestive, stomachic, and peptic ulcers. In this case, a therapeutic effect by other medicinal ingredients can also be obtained.

The dose of the antacid-containing composition of the present invention can be appropriately selected according to the age, weight, symptoms, etc. of the patient. It can be taken once or several times so as to be ~ 1600 mg.

[0021]

According to the present invention, the particle size distribution of magnesium oxide and synthetic hydrotalcite which have been conventionally used as an antacid is selected, and the blending ratio is within a specific range, whereby only safety is excellent. In addition, an antacid-containing composition having both a fast antacid action and a high antacid ability can be obtained. The antacid-containing composition of the present invention is excellent in adhesion of aluminum ions to gastric mucosa, and thereby provides an excellent gastric mucosal protective effect.

[0022]

The present invention will be described below in more detail with reference to examples and comparative examples. The configuration of the present invention is not limited to the following embodiments. Further,% in the following table means% by weight.

Examples 1 to 6 and Comparative Examples 1 to 9 Each antacid having a particle size distribution shown in Table 1 was mixed so as to have a dose shown in Table 2, and magnesium oxide and synthetic hydrotalcite were mixed. An antacid-containing composition consisting of (Examples 1 to 6) and other antacid-containing compositions (Comparative Examples 2 to 9) were prepared,
The following experiment was performed for each antacid-containing composition, and the gastric mucosal protective effects of the examples and comparative examples were compared. In addition,
The particle size distribution of each antacid shown below was measured according to the "particle size test" defined by the Japanese Pharmacopoeia. According to this measuring method, the antacid of the above example has a particle size of 75 to 300 μm.
m is 86.8% by weight, and 94% by weight is a magnesium oxide having a particle size of 75 to 300 μm.
And synthetic hydrotalcite to be contained.

<Protective effect on gastric mucosa (ethanol ulcer)>
DS: After 6-week-old male Donryu rats were purchased from SLC Japan, a solid sample (CE-2, CLEA Japan, Inc.) and tap water were given freely, and the room temperature was 23 ±.
2 ° C., humidity 55 ± 5%, lighting time 7:00 to 19:00
The animals were preliminarily bred for one week under an environment of (light 12 hours, dark 12 hours), and individuals without any abnormalities were used in the following experiments.

After 5 rats in each group were fasted overnight (16 hours) and water-free for 2 hours, each antacid-containing composition was dispersed in distilled water to a concentration of 300 mg / 2.5 ml. It was orally administered at a rate of 2.5 ml / kg (dose: 300 mg / kg). In addition, the same volume of distilled water was administered to the control group. Thirty minutes after the administration, 100% ethanol was orally administered at a rate of 5 ml / kg. One hour after the administration of the ethanol, the carotid artery of the rat was cut off under light anesthesia and killed by exsanguination, and the stomach was removed. Immediately, 10 ml of physiological saline was injected into the excised stomach and further immersed in a 1% formalin solution for fixation. Next, after the fixed stomach was incised along the great bay, the antacid adhered to the gastric mucosa was lightly washed away with distilled water, and the area of the white antacid adhering matter still remaining was determined using an image analyzer (PIAS-V). , Pierce Co., Ltd.)
Was measured. Thereafter, gastric mucosal damage was observed using a binocular stereomicroscope (× 10, SZH, manufactured by Olympus Corporation), and the single diameter and long diameter of the ulcer generated in the glandular stomach were measured. Was determined (ulcer index). The results are also shown in Table 2.

[0026]

[Table 1]

[0027]

[Table 2]

According to Table 2, the ulcer area showing ulcer-like gastric mucosal damage accompanied by bleeding due to ethanol was determined whether magnesium oxide alone (Comparative Example 2) or synthetic hydrotalcite alone (Comparative Example 3). Although it is recognized that the ulcer area is reduced as compared with the control group (Comparative Example 1), the antacid of the present invention combining the antacid-containing composition of these comparative examples, magnesium oxide and synthetic hydrotalcite Comparing the ulcer area with the composition (Examples 1 to 6), the effect of reducing the ulcer area of the antacid-containing composition of the present invention is synergistically enhanced, and the effect is improved by synthesizing with magnesium oxide. It is recognized that a U-shaped effect curve having a peak of 1: 1 with hydrotalcite is shown. On the other hand, when magnesium oxide and aluminum hydroxide were combined (Comparative Examples 4 to 6), the ulcer area was reduced as compared with the control group (Comparative Example 1), but the inhibitory effect was reduced by magnesium oxide alone. Compared with (Comparative Example 2) and aluminum hydroxide alone (Comparative Example 7), a synergistic effect as in the present invention was not obtained, and the combined antacids sanalmin (Comparative Example 8) and cumulite (Comparative Example 9) ) Indicates that the effect of reducing the ulcer area is small. The antacid-containing composition of the present invention in which magnesium oxide having a predetermined particle size distribution and synthetic hydrotalcite are thus combined (Examples 1 to 6).
According to the present invention, the effect of preventing gastric mucosal damage caused by ethanol is exhibited, and furthermore, the effect is maximized by changing the mixing ratio of magnesium oxide and synthetic hydrotalcite within the range of the present invention. be able to. The effect of reducing the ulcer area as much as possible is considered to be a unique effect that cannot be obtained with other antacids (Comparative Examples 2 to 9).

Next, the above Examples 1 to 6 and Comparative Examples 2 to 9
Per stomach pH buffer capacity (buffer time) by the following method
Were compared. <Comparison of buffer time (Fuchs' modified method)> Artificial gastric juice [dilute hydrochloric acid (Japanese Pharmacopoeia standard): 24.0 ml, sodium chloride: 2.0 g, concentrated pepsin (1: 10000): 1.0
5 g, purified water: appropriate amount / total amount 1000 ml]
After accurately taking in a 00 ml beaker, it was immersed in a thermostat maintained at 37 ± 2 ° C., then the thermostat was fixed on a magnetic stirrer, and after inserting an electrode of a pH meter and a thermometer into the beaker, Using a magnetic stirrer, the artificial gastric juice in the beaker was stirred at a rate of about 300 revolutions per minute. After that, artificial gastric juice
When the temperature reached 7 ± 2 ° C., the antacid-containing composition using the antacid having the particle size distribution shown in Table 1 was placed in a beaker so that the amount of the sample shown in Table 3 was obtained while the above stirring was being performed. And the chart of the pH meter recorder was started immediately. After 10 minutes, a new artificial gastric juice prepared separately was poured into the beaker at a rate of 2 ml / min by a metering pump, and the antacid curve of the recorder was adjusted to pH 3.0.
The experiment was continued until was cut.

Table 3 also shows the time of reaching the pH of each antacid-containing composition, the maximum pH, the time of reaching the maximum, and the time during which the pH was maintained at 3.0 to 5.0.

[0031]

[Table 3]

Example 7 and Comparative Example 10 Using antacids having the particle size distribution shown in Table 4, tablets having the following composition were produced by a conventional method using a single-shot tableting machine. The tablets of Example 7 and Comparative Example 10 were obtained. The magnesium oxide used in the examples contains 85.9% by weight of particles having a particle diameter of 75 to 300 μm, and the synthetic hydrotalcite contains 85.9% by weight of particles having a particle diameter of 75 to 300 μm. The magnesium oxide used in the comparative example has a particle size of 7
68.3% by weight of those having a particle size of 5 to 300 μm,
It contains 1.7% by weight (see Table 4). In addition,
Parts in the composition mean parts by weight (the same applies hereinafter).

[0033]

[Table 4] Tablet composition Example 7 Comparative example 10 Magnesium oxide 100 parts 100 parts Synthetic hydrotalcite 100 parts 100 parts Hydroxypropyl cellulose 5 parts 5 parts Crystalline cellulose 60 parts 60 parts Corn starch 12 parts 12 parts Low substitution degree hydroxypropyl cellulose 30 parts 30 parts Magnesium stearate 3 parts 3 parts Total 310 parts 310 parts

Example 8 and Comparative Example 11 Using antacids having the particle size distribution shown in Table 5, tablets having the following composition were produced by a conventional method using a single-shot tableting machine. The tablets of Example 8 and Comparative Example 11 were obtained. The magnesium oxide used had a particle diameter of 75 to 300 μm.
8% by weight, and the synthetic hydrotalcite has a particle size of 75 to
It contains 93.0% by weight of 300 μm (see Table 5).

[0035]

[Table 5] Tablet composition Example 8 Comparative example 11 Magnesium oxide 80 parts-Synthetic hydrotalcite 120 parts-Magnesium hydroxide-60 parts Aluminum hydroxide gel-140 parts Gelatin 5 parts 5 parts Polyvinylpyrrolidone 15 parts 15 parts Crystalline cellulose 80 parts 80 parts Corn starch 17 parts 17 parts Croscarmellose 10 parts 10 parts Magnesium stearate 3 parts 3 parts Total 330 parts 330 parts

Example 9 and Comparative Example 12 Using the antacid having the particle size distribution shown in Table 6, components other than hydroxypropylcellulose in the following components were mixed. 9 kg of purified water 290 m
The mixture obtained by adding 50 g of hydroxypropylcellulose to the mixture and kneading the mixture was then extruded and granulated under ordinary conditions by an extrusion granulation method. The granules of Example 12 were obtained. The magnesium oxide used in the examples contains 89.0% by weight of particles having a particle diameter of 75 to 300 μm, and the synthetic hydrotalcite contains 95.1% by weight of particles having a particle diameter of 75 to 300 μm. (See Table 6).

[0037]

[Table 6] Granule composition Example 9 Comparative Example 12 Magnesium oxide 40 parts-Synthetic hydrotalcite 280 parts-Magnesium carbonate-120 parts Aluminum hydroxide gel-200 parts D-mannitol 50 parts 50 parts Sucrose fatty acid ester 10 parts 10 parts Corn starch 100 parts 100 parts Crystalline cellulose 100 parts 100 parts Hydroxypropyl cellulose 10 parts 10 parts Total 590 parts 590 parts

Example 10 and Comparative Example 13 Components other than hydroxypropylcellulose in the following components were mixed using an antacid having the particle size distribution shown in Table 7, and then this mixture was used. 9 kg of purified water 290
After adding 50 g of hydroxypropylcellulose to a liquid and kneading the mixture, the kneaded product was extruded, granulated under ordinary conditions by a granulation method, dried, sized, and subjected to Example 10 and Comparative Example The granule of Example 13 was obtained. The magnesium oxide used in the examples had a particle size of 75 to 300 μm.
m is 87.2% by weight, the synthetic hydrotalcite contains 88.0% by weight of a particle having a particle diameter of 75 to 300 μm, whereas the magnesium oxide used in the comparative example has a particle diameter of 75%. ３００300 μm is contained in 73.6% by weight, and the synthetic hydrotalcite contains particles having a particle size of 75 to 300 μm in 75.9% by weight (see Table 7).

[0039]

[Table 7] Granule composition Example 10 Comparative Example 13 Magnesium oxide 240 parts 240 parts Synthetic hydrotalcite 60 parts 60 parts Sorbitol 80 parts 80 parts Crystalline cellulose 100 parts 100 parts Corn starch 100 parts 100 parts Hydroxypropyl cellulose 10 parts 10 parts Total 590 parts 590 Department

[Example 11 and Comparative Example 14] Using the antacid having the particle size distribution shown in Table 8, the components having the following composition were mixed, and the mixture was filled in a standard hard capsule by a conventional method. Hard capsules of Example 11 and Comparative Example 14 were obtained. The magnesium oxide used in the examples had a particle size of 7
89.3% by weight of those having a particle size of 5 to 300 μm, and 9% of synthetic hydrotalcite having a particle size of 75 to 300 μm.
The magnesium oxide used in the comparative example has a particle diameter of 75 to 300 μm while containing 3.2% by weight.
3% by weight, the synthetic hydrotalcite has a particle size of 75 to
It contains 70.3% by weight of 300 μm (see Table 8).

[0041]

[Table 8] Hard Capsule Composition Example 11 Comparative Example 14 Magnesium oxide 180 parts 180 parts Synthetic hydrotalcite 120 parts 120 parts Actizol (Asahi Kasei) 40 parts 40 parts Corn starch 30 parts 30 parts Hardened oil 30 parts 30 parts Total 400 parts 400 parts

Examples 7 to 11 and Comparative Examples 10 to 14
, An experiment similar to that of Example 1 above was performed to determine the area of adhesion of these antacids and the area of ulcer by ethanol, and to compare the gastric mucosal protective effect on ethanol ulcer.

Examples 7 to 11 and Comparative Examples 10 to 14
At pH 3.0, maximum pH and time to reach, pH 3.0.
The duration of 0-5.0 was determined by the following method. <Comparison of buffer time (Fuchs' modified method)> Artificial gastric juice [dilute hydrochloric acid (Japanese Pharmacopoeia standard): 24.0 ml, sodium chloride: 2.0 g, concentrated pepsin (1: 10000): 1.0
5 g, purified water: appropriate amount / total amount 1000 ml]
After accurately taking in a 00 ml beaker, it was immersed in a thermostat maintained at 37 ± 2 ° C., then the thermostat was fixed on a magnetic stirrer, and after inserting an electrode of a pH meter and a thermometer into the beaker, Using a magnetic stirrer, the artificial gastric juice in the beaker was stirred at a rate of about 300 revolutions per minute. After that, artificial gastric juice
At the time when the temperature reached 7 ± 2 ° C., while the above stirring was being performed, the antacid-containing compositions of Examples and Comparative Examples were added into a beaker so that the amounts of the samples shown in Table 10 were obtained. Immediately, the pH meter recorder chart was started. After 10 minutes, a new artificial gastric fluid separately prepared was poured into the above beaker at a rate of 2 ml / min by a metering pump, and the experiment was continued until the antacid curve of the recorder fell below pH 3.0. .

Tables 9 and 10 show the results of the above experiments. In each of the above experiments, the granules were used as they were, the tablets were crushed, and the contents of the hard capsules were taken out and used.
In addition, in the case of the doses or sample amounts shown in Tables 9 and 10 below, the amount of the antacid is 300 mg / kg or 300 mg.

[0045]

[Table 9]

[0046]

[Table 10]

Claims (1)

[Claims] (1) 80% by weight or more of the entirety has a particle size of 75 to 30;
0 μm of magnesium oxide and 85% by weight or more of synthetic hydrotalcite having a particle size of 75 to 300 μm are blended in a weight ratio of magnesium oxide: synthetic hydrotalcite = 8: 1 to 1: 8. An antacid-containing composition, comprising: