JPH10236959A - Composition containing antacid agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition containing an antacid agent, excellent in safety, capable of changing a pH in stomach quickly to pH4-6, maintaining the pH region for a long period of time and further aiming at the early absorption and increased absorption amount of the agent by simultaneous blending of a weak electrolytic agent. 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 magnesium hydroxide of which >=85wt.% of the total has 75-300μm particle diameter so as to make a weight ratio of the magnesium oxide to the magnesium hydroxide as (9:1)-(1:9).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an antacid-containing composition, and more particularly to an antacid-containing composition capable of maintaining a gastric pH around 4 to 6.

[0002]

BACKGROUND ART Conventionally, antacids have been used for the treatment of peptic ulcer, hyperacidity, heartburn, gastric discomfort and the like. For example, magnesium oxide, magnesium carbonate Magnesium antacids such as sodium bicarbonate, calcium carbonate, and synthetic hydrotalcite, and aluminum antacids such as aluminum glycinate are commonly used, and the following (1) to (6)
An ideal antacid having all of the above conditions has not yet been developed. (1) The pH in the stomach should not be raised more than necessary
~ 6. (2) It has a strong neutralizing effect, is fast-acting and has long-lasting properties. (3) It does not irritate the gastric mucosa. (4) Does not cause secondary gastric acid secretion. (5) Does not disturb the acid-alkali equilibrium of the body fluid. (6) Does not cause side effects such as diarrhea and constipation.

That is, magnesium-based antacids such as magnesium oxide, magnesium carbonate, and magnesium hydroxide, when taken alone, can transiently increase the gastric pH from 6 to when used in small amounts.
9, but the time to maintain pH 4-6 is shorter. On the other hand, if the dose is increased, this pH range can be maintained for a long time, but it is not preferable because the gastric pH rises more than necessary and becomes alkaline, and furthermore,
This secondarily promotes gastric acid secretion, which not only results in stimulation of the gastric mucosa, but also when the gastric acid is secreted to a certain extent, the stomach becomes overacid, It becomes extremely difficult to maintain the gastric pH around 4 to 6 for a long time. On the other hand, in the case of aluminum antacid,
Not only is it difficult to maintain the gastric pH above 4 but also to maintain the ideal pH range for a long time,
There is a serious drawback that cannot be achieved without using many doses.

In order to obtain an antacid effect and another therapeutic effect, it is necessary to use an antacid in combination with another drug. Particularly, in the case of a weakly acidic drug (weak electrolyte drug), the above-mentioned general-purpose antacid is used. As described above, the stomach pH cannot be sufficiently controlled as described above, so that the weak electrolyte drug used in combination with any of the antacids cannot be sufficiently dissolved and absorbed in the stomach at present. . That is, the dissolution of the weak electrolyte drug, as a factor greatly involved in absorption, the solubility of the physical properties of the drug and the abundance ratio of dissociated and non-dissociated,
These factors vary with gastric pH. For example, a weak electrolyte drug whose solubility increases at a pH of 4 or more is hardly dissolved when the gastric pH is 2 or less, and the amount of the absorbed drug is extremely small. Further, when the weak electrolyte drug is dissolved, the dissociative type and the non-dissociative type coexist, but their abundance changes depending on the pH. It is considered that the non-dissociated type permeates the biological membrane. Further, it is known that the solubility of many weak electrolyte drugs increases at pH 4 to 6. Therefore, when a weak electrolyte drug is used in combination with an antacid, in order to increase the absorption rate of the weak electrolyte drug quickly and greatly, the pH in the stomach is adjusted to _a pH around the pKa of the weak electrolyte drug.
It is important that the weakly electrolyte drug is sufficiently dissolved and that the non-dissociated type is present in a high pH range, and that the pH range is maintained for a long time.

The present invention has been made in view of the above circumstances, and is not only highly safe, but also can quickly and continuously maintain gastric pH around 4 to 6, and is therefore particularly weak. It is an object of the present invention to provide an antacid-containing composition that, when used in combination with an electrolyte drug, can rapidly and greatly absorb a weak electrolyte drug.

[0006]

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 magnesium hydroxide at a predetermined ratio as an antacid, the intragastric pH can be quickly and continuously maintained at around 4 to 6 in a stable manner. Have found the present invention.

That is, according to the present invention, the weight ratio of magnesium oxide having a particle size of 75 to 300 μm to 80% by weight or more and magnesium hydroxide having a particle size of 75 to 300 μm to 85% by weight or more is oxidized. Provided is an antacid-containing composition characterized by being blended so that magnesium: magnesium hydroxide = 9: 1 to 1: 9. Here, in the case of the present invention, it is more effective to further blend a weak electrolyte drug into the antacid-containing composition.

Hereinafter, the present invention will be described in more detail. The antacid-containing composition of the present invention contains magnesium oxide and magnesium hydroxide. Here, the mixing ratio of magnesium oxide and magnesium hydroxide was such that magnesium hydroxide was added in an amount of 0.1 part by weight of magnesium oxide.
It is 11 to 9 parts by weight, preferably 0.25 to 7 parts by weight, more preferably 0.5 to 4 parts by weight. If the mixing ratio of magnesium hydroxide is too low, the gastric pH will rise more than necessary, and it will be difficult to maintain the pH at around 4 to 6, and even if used in combination with a weak electrolyte drug, stable drug absorption will be obtained. I can't get it. On the other hand, if the mixing ratio of magnesium hydroxide is too high, the time for maintaining the gastric pH at 6 or more becomes longer,
Secondary acid secretion is stimulated to stimulate the gastric mucosa, and furthermore, even when used in combination with a weak electrolyte drug, early absorption of the drug cannot be stably obtained.

The amount of the above-mentioned antacid to be added to the whole antacid-containing composition of the present invention is not particularly limited as long as the mixing ratio of magnesium oxide and magnesium hydroxide is within the above range. It can be appropriately selected in consideration of the composition and the dosage form, but generally, the total amount of magnesium oxide and magnesium hydroxide is 20 to 70% by weight, preferably 25 to 70% by weight of the whole antacid-containing composition. It is preferable that the content be 60 to 60% by weight, more preferably 30 to 50% by weight. If the amount of the antacid is too large, it may be difficult to formulate the composition, and if it is too small, it may be difficult to obtain a sufficient antacid effect.

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-mentioned particle size range. If there are too many particles having too large a particle size, the dissolution of magnesium oxide will be slow, and it will be difficult to maintain the optimal gastric pH of pH 4-6. On the other hand, if there are too many particles having too small a particle size, the dissolution of magnesium oxide will be too fast, and the gastric pH will rise more than necessary, which may adversely affect the physiology of the stomach. Internal pH 4-6
The time to maintain becomes shorter.

For the same reason, the antacid-containing composition of the present invention may be used as the above-mentioned magnesium hydroxide,
5% by weight or more, preferably 88% by weight or more, more preferably 90% by weight or more has a particle size of 75 to 300 μm, preferably 75 to 180 μm, more preferably 106 to 180 μm.
Those in the range of m are used. Note that the entire magnesium hydroxide (100%) may be within the above particle size range.

The antacid-containing composition of the present invention, by the above constitution, does not unnecessarily raise the intragastric pH and quickly maintains the pH at 4 to 6 for a long time. Here, the buffer time of the antacid is not particularly limited,
The dosage form, dosage and the like can be varied in various ways.For example, even in the case of a dosage form that is generally said to be coated and hardly dissolved, the gastric pH falls within the above pH range. The time to reach is preferably within 15 minutes, and the time to maintain the pH range is usually preferably 20 minutes or more. In addition, the antacid-containing composition of the present invention is to maintain the pH in the stomach at 4 to 6 after the stomach pH is increased without increasing the stomach pH more than necessary as described above. Is desirably 7.5 or less.

The antacid-containing composition of the present invention is more useful when the above magnesium oxide and magnesium hydroxide are blended as an antacid and a weak electrolyte drug is used in combination. The type is not particularly limited, but considering the effectiveness of the combination, non-steroidal anti-inflammatory drugs are suitable among weak electrolyte drugs, and more preferably those having high solubility at pH 4 to 6, in particular. Desirably, such weak electrolyte drugs include, for example, ibuprofen, indomethacin, phenylbutazone, sodium trimethine, acetylsalicylic acid, sodium salicylate and the like. When the weak electrolyte drug is blended with the antacid-containing composition of the present invention, the blending amount can be appropriately selected depending on the kind of the weak electrolyte drug, the blending purpose, and the like. 5 to 80% by weight, preferably 10 to 70% by weight, more preferably 15 to 60% by weight. If the compounding amount is too large, the stability of the weak electrolyte drug may be deteriorated,
Formulation may be difficult, and if too small, it may be difficult to obtain a sufficient compounding effect.

For the same reason, the mixing ratio of the weak electrolyte drug to the antacid is 0.07 to 0.07 of the total mixing amount of magnesium oxide and magnesium hydroxide in a weight ratio of the weak electrolyte drug. It is preferable to set it to about four times.

[0015] The antacid-containing composition of the present invention may further contain, if necessary, various medicinal ingredients other than the above components, as long as the effects of the present invention are not hindered. In addition to human medicines, animal drugs may be blended, but in consideration of the intended use of the antacid-containing composition of the present invention, for example, sedative hypnotics such as allylisopropylacetylurea and bromvalerylurea, anhydrous A central stimulant such as caffeine is suitably blended, and these can be blended in a usual amount as long as the effects of the present invention are not hindered.

The dosage form of the antacid-containing composition of the present invention is not particularly limited, and examples thereof include tablets, granules, powders,
It is used in various forms such as solid preparations such as capsules, syrups in which magnesium oxide and magnesium hydroxide are dispersed and suspended in powder, granules, powders, and colloids, and liquid preparations such as dispersants. Although it can be prepared by a conventional method, in any case of the dosage form, magnesium oxide and magnesium hydroxide used at the time of formulation,
It is necessary to have the above particle size distribution, usually powdery,
In particular, it is used in powder form. Among the above various dosage forms, those in which magnesium oxide and magnesium hydroxide are in the form of powder, particularly powder, in the preparation are desirable.

In preparing the antacid-containing composition of the present invention into various dosage forms as described above, various additives other than the above-mentioned components may be blended, if necessary, within a range not to impair the effects of the present invention. Can be, for example, when prepared as a solid preparation,
Excipients such as lactose, starch, sucrose, mannitol, crystalline cellulose (for example, Avicel: registered trademark, manufactured by Asahi Chemical Industry Co., Ltd.), and binders such as hydroxypropylcellulose, carboxymethylcellulose, gelatin, sodium carboxymethylcellulose, and gum arabic Disintegrating agents such as carboxymethylcellulose calcium, polyvinylpyrrolidone and crosslinked products thereof, nonionic surfactants such as sucrose fatty acid ester and polyoxysorbitan fatty acid ester, calcium stearate, magnesium stearate, dimethylpolysiloxane, talc, polyethylene glycol, Lubricants such as hardened oils can be blended. If necessary, a coating or sugar coating may be applied. Examples of the coating agent include hydroxypropylcellulose, hydroxypropylmethylcellulose, Eudraggid, 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. The amount of these additives is usually 10 to 75% of the total composition.
%, Preferably 15 to 65% by weight, more preferably 20 to 60% by weight.

In the case of preparing a liquid preparation, excipients such as purified water, ethanol, glycerin, sucrose, propylene glycol, polyethylene glycol, polyoxyethylene sorbitan fatty acid ester, aluminum metahydroxide, agar, and tragacanth gum are used. It can be blended in a range that does not impair the effects of the present invention. In addition, if necessary, other commonly used solubilizing agents, buffering agents, preservatives, fragrances, coloring agents, flavoring agents, etc. It can be blended within a range that does not impair the effects of the present invention. The amounts of these components are the same as in the case of the solid preparation.

The antacid-containing composition of the present invention can be used not only as a medicament for humans but also as an animal drug by taking the composition according to the dosage form according to the usual usage. It works effectively as an antacid to relieve symptoms such as discomfort, heartburn and stomach pain. Further, when the antacid-containing composition of the present invention further contains a weak electrolyte drug,
Since the drug absorbability is excellent, the efficacy of the weak electrolyte drug can be sufficiently obtained. For example, if the weak electrolyte drug is a non-steroidal anti-inflammatory drug, toothache, pain after tooth extraction, sore throat, joint pain, low back pain, Analgesia such as muscle pain, menstrual pain, chills,
It also exerts a sufficient drug effect such as analgesia at the time of acute inflammation such as fever at the time of fever, bruise and sprain, and anti-inflammatory.

The dose of the antacid-containing composition of the present invention can be appropriately selected according to the age, body weight, symptoms, etc. of the patient. It is preferable to take 1 to 3 times a day as 25 to 1500 mg.

[0021]

According to the present invention, if the particle size distribution of magnesium oxide and magnesium hydroxide conventionally used as antacids is selected and the blending ratio in a specific range, only excellent safety can be obtained. In addition, a antacid-containing composition which neutralizes gastric acid quickly and has excellent antacid action is obtained. According to the antacid-containing composition of the present invention,
By taking the drug, the gastric pH can be quickly adjusted to pH 4 to 6, and the pH range can be maintained for a long time. The antacid-containing composition of the present invention contains a weak electrolyte drug, particularly pH 4-6.
When a weak electrolyte drug whose solubility rapidly increases is further added, the early absorption of the weak electrolyte drug and an increase in the absorption amount can be brought about, and the therapeutic effect of the weak electrolyte drug can be sufficiently obtained.

[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.

[Example 1 and Comparative Examples 1-4] Each antacid having a particle size distribution shown in Table 1 was mixed so as to have the proportion of the sample shown in Table 2, and magnesium oxide and magnesium hydroxide were mixed. (Weight ratio; 1: 1) and the other antacid-containing composition (Comparative Example 1)
-4) were prepared, and the following experiment was performed for each antacid-containing composition, and the buffering capacity (time) of the two antacid formulations was compared. In addition, the particle size distribution of each antacid shown below was measured according to the "particle size test" prescribed by the Japanese Pharmacopoeia. According to this measurement method, the antacid of the above example was composed of magnesium oxide containing 84.9% by weight of a particle having a particle size of 75 to 300 μm, and a particle having a particle size of 75 to 300 μm.
m) and 95.5% by weight of magnesium hydroxide. <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, immersing it in a thermostat maintained at 37 ° C. ± 2 ° C., fixing the thermostat on a magnetic stirrer, inserting an electrode of a pH meter and a thermometer into the beaker, Using a magnetic stirrer, the artificial gastric juice in the above beaker was dispensed for about 300
The mixture was stirred so as to have a rotation ratio. Thereafter, when the temperature of the artificial gastric juice reached 37 ° C. ± 2 ° C., the antacid-containing composition was added to the beaker so that the amount of the sample shown in Table 2 was obtained while stirring, and immediately. The chart of the pH meter recorder was started. After a lapse of 10 minutes, a new artificial gastric juice prepared separately was poured into the above-mentioned 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 4.0. .

Table 2 shows that one minute after each antacid-containing composition,
The pH after minutes and the time during which the pH was maintained at 4.0 to 6.0 are also described.

[0025]

[Table 1]

[0026]

[Table 2]

According to Table 2, magnesium oxide and magnesium hydroxide (weight ratio;
1: 1) 10 minutes after addition to the artificial gastric juice, the composition
), And the time for maintaining pH 4-6 thereafter is also noticeably longer than for other antacid formulations.

[Examples 2 to 8 and Comparative Examples 5 to 10] Table 3
The magnesium oxide and magnesium hydroxide having the particle size distribution shown in Table 4 were mixed with ibuprofen so as to have the proportions of the amounts of the samples shown in Table 4 to prepare compositions consisting only of these. The buffer capacity (time) was compared by the same method as in the above. The results are also shown in Table 4. According to Table 3, the magnesium oxide used in the examples contains 88% by weight having a particle size of 75 to 300 μm, and the magnesium hydroxide has a particle size of 75 to 300 μm.
It contains 92.3% by weight of μm.
On the other hand, the magnesium oxide used in the comparative example has a particle size of 75%.
３００300 μm is contained in 68.3% by weight, and magnesium hydroxide is contained in a particle size of 75-300 μm in 75.4% by weight.

[0029]

[Table 3]

[0030]

[Table 4]

According to Table 4, the antacid-containing composition of the present invention was used in combination with ibuprofen by varying the mixing ratio of magnesium oxide and magnesium hydroxide within the range of the present invention. 10 minutes after the addition to the artificial gastric juice, the pH was around 5-7, and the pH was
In contrast to the case where magnesium oxide having a particle size distribution outside the range of the present invention is used alone (Comparative Example 5), magnesium hydroxide having a particle size distribution outside the range of the present invention is used alone. (Comparative Example 6), a combination of magnesium oxide having a particle size distribution outside the range of the present invention and magnesium hydroxide (Comparative Example 8) and a magnesium oxide having a particle size distribution outside the range of the present invention or When magnesium hydroxide and ibuprofen were used in combination (Comparative Examples 9 and 10), p
It is recognized that H7-10 is high, and the time for maintaining pH 4-6 is short thereafter. In the case of ibuprofen alone (Comparative Example 7), almost no antacid action was observed.

[Examples 9 to 15 and Comparative Examples 11 to 14] <Pharmacokinetics of ibuprofen in combination with ibuprofen> Magnesium oxide, magnesium hydroxide, and ibuprofen of Examples and Comparative Examples having a particle size distribution shown in Table 5 Are mixed so that the mixing ratio of each component becomes the ratio of the dosage shown in Table 6, and the composition is prepared so that the amount of each drug in one capsule becomes the dosage shown in Table 6. Beagle dogs (male,
1 to 2 years old, body weight 8 to 12 kg, 6 animals per group), 1 ml of blood was collected from the forelimb vein with time, plasma was separated from the blood by centrifugation, and ibuprofen in the plasma was collected. It was quantified by a conventional method using HPLC. From the relationship between the aging time and the measured value of the plasma concentration of the drug, the pharmacokinetic parameters of the time to reach the maximum blood concentration (T _max ), the maximum blood concentration (C _max ), and the area under the blood concentration time curve (AUC) were determined. I asked. Table 6 also shows the average value of each parameter.
As is clear from Table 5, the magnesium oxide used in Examples had a particle diameter of 75 to 300 μm.
1% by weight, and magnesium hydroxide has a particle size of 75 to 3
It contains 94.5% by weight of 00 μm.

[0033]

[Table 5]

[0034]

[Table 6]

According to Table 6, the composition containing the antacid of the present invention (Examples 9 to 15) and ibuprofen alone (Comparative Example 1)
1), magnesium oxide and magnesium hydroxide are out of the range of the particle size distribution of the present invention, ibuprofen + magnesium oxide (Comparative Example 12), ibuprofen + magnesium hydroxide (Comparative Example 13), ibuprofen + magnesium carbonate + synthetic hydrogel When compared with the composition of talcite (Comparative Example 14), T _{max of the} time to reach the maximum blood concentration indicating the speed of absorption of ibuprofen is faster in the antacid-containing composition of the present invention than in the comparative example. It is recognized that. Furthermore, the AUC of the area under the blood concentration-time curve, which is an index of the amount of ibuprofen absorbed, was also found to be higher in the antacid-containing composition of the present invention than in the comparative example. The above results demonstrate that the antacid-containing composition of the present invention, when used in combination with ibuprofen, one of the weak electrolyte drugs, speeds up the absorption of the drug and sufficiently improves the absorption.

Example 16 and Comparative Example 15 Using antacids having the particle size distribution shown in Table 7 and mixing the components so as to have the following composition, a single shot tableting machine was used. The tablets of Example 16 and Comparative Example 15 were obtained. The magnesium oxide used had a particle size of 7
86% by weight of 5-300 μm is contained, and magnesium hydroxide is 87.5% by weight of 75-300 μm of particle size (see Table 7). Parts in the composition mean parts by weight (hereinafter the same).

[0037]

[Table 7] Tablet composition Example 16 Comparative example 15 Ibuprofen 75 parts 75 parts Anhydrous caffeine 15 parts 15 parts Magnesium oxide 50 parts 30 parts Magnesium hydroxide 50 parts-magnesium carbonate-105 parts Hydroxypropyl cellulose 10 parts 15 parts Crystalline cellulose 57 parts 17 parts Corn starch 10 parts 10 parts Carboxymethyl cellulose 20 parts 20 parts Magnesium stearate 3 parts 3 parts Total 290 parts 290 parts

[Example 17 and Comparative Example 16] Using an antacid having the particle size distribution shown in Table 8, the components were mixed so as to have the following composition, and then a single-shot tableting machine was used. The tablets of Example 17 and Comparative Example 16 were obtained. The magnesium oxide used had a particle size of 7
86.0% by weight of those having a particle diameter of 5 to 300 μm, and magnesium hydroxide having a particle diameter of 75 to 300 μm.
It contains 5% by weight (see Table 8).

[0039]

[Table 8] Tablet composition Example 17 Comparative example 16 Ibuprofen 75 parts 75 parts Allylisopropylacetyl urea 10 parts 10 parts Anhydrous caffeine 20 parts 20 parts Magnesium oxide 30 parts-Magnesium hydroxide 120 parts-Magnesium carbonate-60 parts Synthetic hydrotalcite-120 Parts Gelatin 5 parts 5 parts Polyvinylpyrrolidone 15 parts 15 parts Crystalline cellulose 75 parts 45 parts Corn starch 17 parts 17 parts Croscarmellose 10 parts 10 parts Magnesium stearate 3 parts 3 parts Total 380 parts 380 parts

EXAMPLE 18 AND COMPARATIVE EXAMPLE 17 Using the antacid having the particle size distribution shown in Table 9, components other than hydroxypropylcellulose in the following components were mixed. 4 kg of purified water 340 in advance
After adding 68 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 18 and Comparative Example The granule of Example 17 was obtained. The magnesium oxide used in the examples had a particle size of 75 to 300 μm.
m is 88.9% by weight, and magnesium hydroxide contains 94.7% by weight of a particle having a particle size of 75 to 300 μm, whereas magnesium oxide used in the comparative example is:
Containing 72.7% by weight of a particle having a particle size of 75 to 300 μm,
Magnesium hydroxide contains 76.7% by weight of particles having a particle size of 75 to 300 μm (see Table 9).

[0041]

[Table 9] Granule composition Example 18 Comparative example 17 Phenylbutazone 200 parts 200 parts Magnesium oxide 20 parts 20 parts Magnesium hydroxide 140 parts 140 parts Gelatin 3 parts 3 parts D-mannitol 50 parts 50 parts Sucrose fatty acid ester 10 parts 10 parts Crystal Cellulose 37 parts 37 parts Maize starch 50 parts 50 parts Hydroxypropyl cellulose 10 parts 10 parts Total 520 parts 520 parts

EXAMPLE 19 AND COMPARATIVE EXAMPLE 18 An antacid having the particle size distribution shown in Table 10 was used, and components other than hydroxypropylcellulose in the following components were mixed. 7 kg of purified water in advance
A solution prepared by dissolving 52 g of hydroxypropylcellulose in 0 ml was added and kneaded. Then, the kneaded product was extruded, granulated under ordinary conditions by a granulation method, dried, sized, and subjected to Example 19 and Comparative Example The granules of Example 18 were obtained. In addition,
The magnesium oxide used in the examples had a particle size of 75 to 300.
μm and 94.3% by weight of magnesium hydroxide and 75 to 300 μm in particle size, whereas magnesium oxide used in Comparative Examples has a particle size of 75 to 300 μm. 70.5% by weight contains 300 μm, and 72.9% by weight magnesium hydroxide contains 75 to 300 μm particle diameter (see Table 10).

[0043]

[Table 10] Granule composition Example 19 Comparative Example 18 Phenylbutazone 200 parts 200 parts Magnesium oxide 60 parts 60 parts Magnesium hydroxide 120 parts 120 parts Sorbitol 50 parts 50 parts Crystalline cellulose 50 parts 50 parts Corn starch 40 parts 40 parts Hydroxypropyl cellulose 10 parts 10 copies Total 530 copies 530 copies

Example 20 and Comparative Example 19 Using an antacid having the particle size distribution shown in Table 11, 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 20 and Comparative Example 19 were obtained. The magnesium oxide used in the examples contained 87.7% by weight of a particle having a particle size of 75 to 300 μm, and the magnesium hydroxide contained 9% of a particle having a particle size of 75 to 300 μm.
In contrast to the content of 2.2% by weight, the magnesium oxide used in the comparative example had a particle diameter of 75 to 300 μm.
7% by weight, and magnesium hydroxide has a particle size of 75-3.
It contains 73.7% by weight of 00 μm (see Table 11).

[0045]

[Table 11] Hard Capsule Composition Example 20 Comparative Example 19 Indomethacin 25 parts 25 parts Magnesium oxide 100 parts 100 parts Magnesium hydroxide 50 parts 50 parts Actisol (Asahi Kasei) 40 parts 40 parts Corn starch 55 parts 55 parts Hardened oil 30 parts 30 parts Total 300 parts 300 copies

[Example 21 and Comparative Example 20] A mixture of acetylsalicylic acid and corn starch in the following components was used as an antacid having a particle size distribution shown in Table 12 as a first layer. The mixture of the components of the second
As a layer, tableting was performed under ordinary conditions using a rotary tableting machine to obtain tablets of Example 21 and Comparative Example 20. The magnesium oxide used in the examples had a particle size of 75 to 300 μm.
m is 88.6% by weight, and magnesium hydroxide is 92.5% by weight having a particle diameter of 75 to 300 μm (see Table 12).

[0047]

[Table 12] Tablet composition Example 21 Comparative example 20 Acetylsalicylic acid 330 parts 330 parts Corn starch 10 parts 10 parts Magnesium oxide 128 parts-Magnesium hydroxide 32 parts-Magnesium carbonate-110 parts Aluminum glycinate-50 parts Gelatin 3 parts 3 parts Polyvinylpyrrolidone 13 parts 13 parts Croscarmellose 10 parts 10 parts Magnesium stearate 4 parts 4 parts Total 530 parts 530 parts

Example 22 and Comparative Example 21 Components other than hydroxypropylcellulose in components having the following composition were mixed using an antacid having a particle size distribution shown in Table 13, and then this mixture was used. 6 kg of purified water 26
A mixture prepared by dissolving 76 g of hydroxypropylcellulose in 0 ml was kneaded, and then the kneaded product was extruded, granulated under ordinary conditions by a granulation method, dried, sized and subjected to Example 22 and Comparative Example The granule of Example 21 was obtained. In addition,
The magnesium oxide used in the examples had a particle size of 75 to 300.
85.7% by weight, and magnesium hydroxide contains 89.8% by weight of particles having a particle size of 75 to 300 μm (see Table 13).

[0049]

[Table 13] Granule composition Example 22 Comparative example 21 Ibuprofen 150 parts 150 parts Magnesium oxide 100 parts-Magnesium hydroxide 60 parts-Magnesium carbonate-140 parts Aluminum hydroxide gel-80 parts Gelatin 5 parts 5 parts D-mannitol 70 parts 70 parts Crystal Cellulose 90 parts 40 parts Corn starch 40 parts 30 parts Hydroxypropyl cellulose 15 parts 15 parts Total 530 parts 530 parts

Examples 16 to 22 and Comparative Examples 15 to 2
For Example 1, the same experiment as in Example 1 was performed, and their buffering capacities (time) were compared. Table 14 shows the results.
In the experiment, the granules were used as they were, the tablets were crushed, and the hard capsules were used by taking out the contents and using beakers so that the total amount of the antacid contained in each sample was 200 mg. Was added.

[0051]

[Table 14]

According to Table 14, even when the antacid-containing composition of the present invention was used in various dosage forms in combination with various drugs, any of the compositions was found to be 10 minutes after the start of pH measurement. The pH is around 4-6, and the subsequent pH 4-6
Is also long.

Claims (2)

[Claims] (1) 80% by weight or more of the entirety has a particle size of 75 to 30;
A weight ratio of magnesium oxide of 0 μm and magnesium hydroxide having a particle size of 75 to 300 μm of 85% by weight or more is magnesium oxide: magnesium hydroxide =
An antacid-containing composition characterized by being blended so as to be 9: 1 to 1: 9. 2. The antacid-containing composition according to claim 1, further comprising a weak electrolyte drug.