WO2004082692A1

WO2004082692A1 - Actacid composition

Info

Publication number: WO2004082692A1
Application number: PCT/JP2004/003479
Authority: WO
Inventors: Hiroaki Kuga; Yuichiro Kano; Akihiro Tamada; Hiroyuki Kawashima
Original assignee: Kowa Co., Ltd.
Priority date: 2003-03-18
Filing date: 2004-03-16
Publication date: 2004-09-30
Also published as: CN1761474A; KR101173580B1; TW200509950A; JP4669391B2; HK1087034A1; KR20050107577A; TWI344844B; JPWO2004082692A1; CN100342860C

Abstract

An actacid composition containing no aluminum, which comprises magnesium hydroxide, sodium hydrogencarbonate and calcium carbonate and exhibits a maximum reaching pH in the modified Fuchs method of 5 to 7. The actacid composition combines the fast-acting property and the persistence with respect to its deacidification action and does not cause the rebounding secretion of an acid and further does not contain aluminum.

Description

Antacid composition

Technical field

The present invention combines the fast-acting and long-lasting action of acid neutralization, and causes a reactive acid secretion.

In addition, the present invention relates to an antacid composition containing no aluminum.

Background art

Gastrointestinal medications generally relieve symptoms such as excessive gastric acidity, heartburn, discomfort in the stomach, stomach bloating, leaning, heavy stomach, chest stomach, belching, brushing, vomiting, excessive drinking, and stomach pain. Therefore, most commercially available gastrointestinal drugs contain antacids that neutralize hydrochloric acid secreted into the stomach and inactivate pepsin.

Gastrointestinal drugs containing antacids are required to neutralize stomach acid immediately after taking the drug, and to quickly relieve symptoms, to neutralize secreted hydrochloric acid, and to maintain its effect. . It is also an important factor that the pH in the stomach does not cause the repulsive acid secretion caused by tilting to the alkaline side.

However, in reality, it is difficult to meet these requirements with a single component antacid. On the other hand, among antacids, it is known that antacids containing aluminum have long-lasting properties. For this reason, most of the commercially available gastrointestinal drugs containing antacids contain aluminum. Actually, fast-acting antacids such as magnesium hydroxide and sodium hydrogencarbonate, and metasilicate Combinations with persistent antacids such as magnesium acid aluminate, dried aluminum hydroxide gel and magnesium aluminate, coprecipitates thereof, and solid solutions thereof are used as the compounding components.

However, recently, long-term intake of aluminum and aluminum encephalopathy There is also a report on the association with dementia of the mer type.For gastrointestinal drugs containing antacids that are often taken over a relatively long period of time, it is desired to develop a treatment that does not contain aluminum. I have.

As an antacid formulation containing no aluminum, for example, an antacid composition comprising calcium hydrogen phosphate or the like and an antacid containing no aluminum has been reported, and the pH in the stomach can be increased by the composition. It is moderately controlled, and the duration of action can be maintained (Japanese Patent Application Laid-Open No. 11-124,334). However, it is necessary to increase the dose to obtain a sufficient antacid effect. As a result, problems such as reduced compliance and restrictions on the combination of other medicinal ingredients have arisen, and are not always satisfactory. Disclosure of the invention

Accordingly, an object of the present invention is to provide an antacid composition which has both quick action and long-lasting acid neutralizing action, does not cause reactive acid secretion, and further does not contain aluminum.

In view of such circumstances, the present inventors have conducted intensive studies on the antacid composition.As a result, if the three components of magnesium hydroxide, sodium hydrogen carbonate and calcium carbonate are blended so as to exhibit a constant pH, aluminum is contained. Instead, the present inventors have found that an antacid composition having rapid and sustained action of acid neutralization and no reactive acid secretion can be obtained, and thus completed the present invention.

That is, the present invention relates to an antacid composition containing no aluminum, which contains magnesium hydroxide, sodium hydrogen carbonate and calcium carbonate, has a maximum pH of 5 to 7 in a modified Fox test, and does not contain aluminum. It offers things.

According to the present invention, it is possible to obtain an antacid composition which has both quick action and long-lasting action of acid neutralization, does not cause repulsive acid secretion, and further does not contain aluminum. Therefore, the antacid composition of the present invention is useful as an antacid compounded in gastrointestinal drugs. You. BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a diagram showing a change in pH determined by a modified Fuchs test. BEST MODE FOR CARRYING OUT THE INVENTION

Examples of the magnesium hydroxide used in the present invention include commercially available products such as Kyo-Sui Mag (manufactured by Kyowa Chemical) and magnesium hydroxide (manufactured by Tomita Pharmaceutical). The mixing amount of magnesium hydroxide is preferably from 0.01 to 20% by weight, more preferably from 0.1 to 10% by weight, and particularly preferably from 1 to 7% by weight, based on the total amount of the preparation.

Examples of the sodium hydrogen carbonate used in the present invention include commercially available products such as sodium bicarbonate (made by Asahi Glass) and sodium hydrogen carbonate (made by Oriental Pharmaceutical Industries). The compounding amount of sodium hydrogencarbonate is preferably 1 to 50% by weight, more preferably 5 to 40% by weight, and particularly preferably 10 to 30% by weight based on the total amount of the preparation. Examples of the calcium carbonate used in the present invention include calcium carbonate, precipitated calcium carbonate, porei containing calcium carbonate as a main component, Borei Sekiishi or squid bone. Commercially available products include precipitated calcium carbonate (manufactured by Bihoku Powder Chemical Industry), precipitated calcium carbonate (manufactured by Oriental Yakuhin Kogyo) and the like. The amount of the carbonated calcium is preferably from 10 to 80% by weight, more preferably from 15 to 70% by weight, and particularly preferably from 20 to 60% by weight, based on the total amount of the preparation.

The antacid composition of the present invention contains the above three components, and has a maximum reached PH of 5 to 7 in a modified Fuchs test. Is necessary to prevent That is, if the maximum reached PH is less than 5, sufficient immediate action and sustainability cannot be obtained, and if it exceeds 7, reactive acid secretion occurs. Here, the modified Fox method test is a test method performed under the following conditions. That is, in 50 mL of 0.1 N hydrochloric acid kept at 37 ° C. and 2 ° C., the antacid composition corresponding to one dose was added. In addition, the test is started, and the pH is measured every 2 minutes up to 10 minutes after the start to evaluate the rapid effect of the antacid effect. Further, after 10 minutes from the start, 0.1 N hydrochloric acid is added dropwise at a rate of 2 mL / min, and the pH is measured every 2 minutes to evaluate the sustainability of the antacid effect. During the test, keep stirring the test solution with a stirrer.

In order to obtain the highest attainment pH as described above, the mass ratio of magnesium hydroxide to sodium hydrogen carbonate is preferably 1: 0.1 to 15, more preferably 1: 1 to 12, 1: 3 to 9 are particularly preferred. The mass ratio between 7K magnesium oxide and calcium carbonate is preferably 1: 1 to 40, more preferably 1: 3 to 30, and particularly preferably 1: 5 to 20. The mass ratio of sodium hydrogencarbonate to calcium carbonate is preferably from 0.1 to 15: 1 to 40, more preferably from 1 to 12: 3 to 30, and particularly preferably from 3 to 9: 5 to 20.

The method for producing the antacid composition of the present invention is not particularly limited, and can be produced by, for example, uniformly mixing magnesium hydroxide, sodium hydrogen carbonate and calcium carbonate with a commonly used machine.

The following drugs and additives can be used in the antacid composition of the present invention as needed. Examples of the drug include antacids, stomachic, digestive medicine, intestinal medicine, antidiarrheal, analgesic / spasmodic, gastric mucosa repair agent, vitamins, antifoaming agents, etc.

Examples of the antacid other than the above include, for example, magnesium carbonate, aminoaminoacetic acid, mouth extract, magnesium silicate and the like.

Examples of the stomachic include, but are not limited to, anis seed, aloe, fennel, konkon, zaku, prolonged life grass, oegon, oakbak, oren, processed garlic, gaju, katsuko, calamus root, dried ginger, citrus, kid, keich, gentian, gentian Kopoku, Goshu, Pepper, Colombo, Consulango, Sansho, Yamana, Shisoshi, Shukusha, Shokyouyo, Shoshuku, Blue Peel, Ishimine, Centaurium Grass, Sempuri, Soju, Soyou, Great Fragrance, Daiyo, Chikusenjin , Cock, capsicum, spruce, animal gall (including urethane), oyster, nutmeg, nin Gin, heart strength (including syrup strength), repellency (hihatsu), biyakuju, hop, homica extract, rape leaf (silica), mockup, jakchi, ryutan, ryoukiyo, fennel oil, keisho oil, shoshoyo oil , Fallow oil, spruce oil, heart oil, lemon oil, 1-mentil, dl-men! No.

Digestive agents include, for example, starch digestive enzymes, protein digestive enzymes, fat digestive enzymes, fibrin digestive enzymes, ursodesoxycholate, oxycholanates, colic acid, bile powder, bile extract (end) , Dehydrocholic acid, animal bile (including urethane) and the like.

Examples of the intestinal medicine include live intestinal bacteria components, red buds, red buds, asenyaku, bamboo shoots, sweet potatoes, gennoshoko and the like.

Examples of antidiarrheals include acrylonitrile, berberine chloride, guaiacol, creosote, phenyl salicylate, guaiacol carbonate, berberine tannate, bismuth subsalicylate, bismuth subnitrate, bismuth subcarbonate, bismuth subgallate Examples include tannic acid, albumin tannate, methylene thymol tannin, thiol orcin, pectin, medicinal charcoal, calcium lactate, aceniak, squid, opaque, oren, kujin, gennoshoko, quintuplets, hawthorn, sempuri, and squid.

Examples of analgesic and antispasmodic agents include oxyphencycline hydrochloride, dicycline hydrochloride, methixene hydrochloride, scopolamine hydrobromide, methyl atatopine bromide, methyl anisotropine bromide, methyl scopolamine bromide, methyl bromide- 1-hyoscyamine, methylpenactidium bromide, belladonna extract, isopropamide iodide, diphenylpiperidinomethyldioxolan iodide, oral extract, oral root total alkaloid citrate, Examples include papaverine hydrochloride, ethyl aminobenzoate, engosaku, kanzo, kopoku, and peony. Examples of the gastric viscosity repair agent include sodium azulene sulfonate, aldioxa, glycyrrhizic acid and salts thereof and licorice extract, L-glutamine, copper copper chlorophyllin potassium, copper copper chlorophyllin sodium, histidine hydrochloride, pig gastric wall pepsin degradation product, Porcine gastric wall acid hydrolyzate, methylmethionine sulfonium chloride, Akebashi Kashiwa, Engosaku, Kanzo, and the like.

Examples of vitamins include nicotinic acid amide, calcium pantothenate, Piochin, vitamins or their derivatives or salts thereof, vitamin B ₂ or its derivatives or salts thereof, vitamin B ₆ or a derivative or a salt thereof, bi evening Min C Or a derivative thereof or a salt thereof.

Examples of the antifoaming agent include dimethylpolysiloxane.

Examples of additives include excipients, binders, disintegrants, lubricants, coloring agents, flavoring agents, and the like.

Examples of the excipient include lactose, starches, crystalline cellulose, sucrose, mannitol, light caffeic anhydride and the like. Examples of the binder include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, alpha-monostarch, bolivier pyrrolidone, polyvinyl alcohol, and pullulan. Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, crosbopidone, corn starch, low-substituted hydroxypropyl cellulose and the like. Lubricants include magnesium stearate, talc and the like. Examples of the coloring agent include tar dyes and iron sesquioxide. Flavoring agents include stevia, aspartame, flavors and the like.

The antacid composition of the present invention is manufactured into powders, granules, tablets, chewable tablets, film-coated tablets, dragees, drinks, soft capsules, hard capsules, gels, etc. according to the purpose. it can. Example Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited thereto.

Example 1

Take 33mg of magnesium hydroxide (magnesium hydroxide: manufactured by Tomita Pharmaceutical Co., Ltd.), 300mg of sodium hydrogen carbonate (sodium bicarbonate: manufactured by Asahi Glass) and 40Omg of precipitated calcium carbonate (precipitated calcium carbonate: manufactured by Bihoku Powder Chemical Industry Co., Ltd.). The mixture was mixed to obtain an antacid composition.

Example 2

33 mg of magnesium hydroxide, 20 Omg of sodium hydrogen carbonate and 50 Omg of precipitated carbon dioxide were taken and uniformly mixed in a mortar to obtain an antacid composition.

Example 3

67 mg of magnesium hydroxide, 30 Omg of sodium hydrogen carbonate and 50 Omg of precipitated carbon dioxide were taken and uniformly mixed in a mortar to obtain an antacid composition.

Example 4

67 mg of magnesium hydroxide, 20 Omg of sodium hydrogen carbonate and 50 Omg of precipitated carbon dioxide were taken and uniformly mixed in a mortar to obtain an antacid composition.

Example 5

33 mg of magnesium hydroxide, 20 Omg of sodium hydrogen carbonate and 60 Omg of precipitated carbon dioxide were taken and uniformly mixed in a mortar to obtain an antacid composition.

Example 6

33 mg of magnesium hydroxide, 20 Omg of sodium hydrogencarbonate and 433 mg of precipitated carbon dioxide were taken and uniformly mixed in a mortar to obtain an antacid composition.

Comparative Example 1

33 mg of magnesium hydroxide and 300 mg of sodium bicarbonate were taken and uniformly mixed in a mortar to obtain an antacid composition.

Comparative Example 2 30 Omg of sodium bicarbonate and 40 Omg of precipitated calcium carbonate were taken and uniformly mixed in a mortar to obtain an antacid composition.

Comparative Example 3

33 mg of magnesium hydroxide and 40 Omg of precipitated calcium carbonate were taken and uniformly mixed in a mortar to obtain an antacid composition.

Comparative Example 4

A formulation A2 described in JP-A-58-4725, pages 4 and 5, was prepared. That is, 381.lmg of sodium bicarbonate, 300.5mg of calcium carbonate, 14.7mg of calcium phosphate, 22mg of magnesium hydroxide and 14.7mg of titanium oxide are mixed uniformly in a mortar to prepare an antacid composition. Obtained.

Test example 1

Using the antacid compositions obtained in Examples 1 to 6 and Comparative Examples 1 to 4, the immediate effect and persistence of antacid activity were examined in a modified Fuchs test. The index of the immediate effect of the antacid effect was the pH 10 minutes after the start of the test at which the pH reached the maximum, and the index of the sustained antacid effect was the time until the pH became 3.5 or less. In the modified Fuchs test, if the pH after 10 minutes is 6 or more, it is regarded as fast-acting, and if the time until the pH becomes 3.5 or less is 40 minutes or more, it is persistent Was considered. The index of rebound acid secretion was evaluated at the highest pH reached. The results are shown in Table 1, Table 2 and Figure 1.

table 1

—Otsu

According to Table 1, Table 2 and FIG. 1, among magnesium hydroxide, sodium hydrogencarbonate and calcium carbonate, Comparative Example 1 lacking calcium carbonate had a maximum attained pH of about 2 and did not have sufficient antacid activity. Was. In addition, the highest attainment pH (after 10 minutes) of Comparative Example 4 was 7.3, which revealed that there was a possibility that reactive acid secretion might occur. On the other hand, in Comparative Example 2 lacking magnesium hydroxide and Comparative Example 3 lacking sodium hydrogen carbonate, the duration of the antacid effect was insufficient. On the other hand, Examples 1 to 6 in which magnesium hydroxide, sodium hydrogen carbonate and calcium carbonate were blended had a long acid neutralization duration and a maximum reached pH after 10 minutes of 6 to 7 and showed a rapid effect. Yes, recoil It is considered that no specific acid secretion occurs.

Production Example 1

Sodium bicarbonate 900 g, magnesium hydroxide 100 g, calcium carbonate

1 200 g, Rohto extract 3 times powder 90 g, Simpli powder 28 g, Piodias Yuichize

24 g, lipase 15 g, hydroxypropylcellulose 150 g, carmellose calcium 180 g and crystalline cellulose 8777 g were fed to a high-speed stirring granulator (High-speed mixer: Fukae Kogyo). Then, ethanol was added, kneaded, granulated, dried, and sized to obtain sized powder. 36 g of magnesium stearate was added to the sized powder, and the mixture was compression-molded with a tableting machine to produce 600 tablets of 600 mg per tablet.

Claims

The scope of the claims

1. An antacid composition containing no aluminum, containing τ マグネシウム magnesium oxide, sodium hydrogen carbonate and calcium carbonate, and having a maximum ρΗ of 5 to 7 in a modified Fuchs test.

2. The antacid composition according to claim 1, wherein the mass ratio of τΚ magnesium oxide to sodium hydrogen carbonate is 1: 0.1 to 15.

3. The antacid composition according to claim 1 or 2, wherein the mass ratio of magnesium hydroxide to calcium carbonate is 1: 1 to 40.

4. The antacid composition according to any one of claims 1 to 3, wherein the mass ratio of sodium bicarbonate to calcium carbonate is 0.1 to 15: 1 to 40.