DE1467253A1 - Process for the preparation of an agent against gastric acidification - Google Patents

Description

ARMOR PHARMACEUTICAL COMPAiTY, Chicago, 111., USA

"Process for the production of an agent against gastric acidosis"

The invention relates to a method for producing an agent against gastric acidification using aluminum and magnesium by precipitating them together from an aqueous solution, whereby the metals, based on the weight of AlpO: MgO, in proportions from 4: 1 to 1:10. This method is characterized in that the coprecipitate from an aqueous solution with a pH between about 9 and about 10 is precipitated and the reaction by introducing a to maintain the pH between about 6 and about 10 sufficient carbon dioxide is terminated.

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11 Ate 3 No. 1 Sofc 5 «te» AndwwVQ «. »· * · ^V

Anti-acidic agents are now becoming more common in the treatment of peptic ulcers, more gastric Hyperacidity and dyspepsia applied. Gwilt, Livingstone and Robertson describe in the Journal of Pharmacy and Pharmacology, X No. 12 pp. 770-775 (1958) the properties of ideal remedies against acidification. It is stated that this their maximum neutralizing effect in the shortest possible Time should show that you should neutralize a sufficient amount of gastric hydrochloric acid and its effects should be maintained in the stomach during the normal period of digestion, but that a possibly large one Excess over the amounts required to neutralize the free gastric acid should not cause alkalization and that they should raise the pH of the stomach contents to a level at which pepsin activity is significant is reduced, but not completely inhibited. Furthermore, sufficient and repeated doses should be used for the Acid sufferers should be palatable and their use should not be laxative, or constipative other side effects, such as stomach irritation. In addition to these factors, the anti-acidic agent should be used be cheap and it must not be significantly damaged in any way as it ages. The authors are the various findings in the literature regarding what is desirable for an ideal anti-acidic remedy pH ranges summarized and found that a pH

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in the range from about 3 to about 5 is obviously optimal in order to achieve sufficient relief from hyperacidity, in particular, if there is an ulcer site, ensure and at the same time that there is sufficient residual at this pH Pepsin activity remains to avoid secondary indigestion.

As a result, in modern therapeutic practice, the administration of excessive amounts of powerful agents becomes against over-acidification, such as sodium bicarbonate, avoided and acid buffers such as aluminum hydroxide used instead, to adjust the gastric acidity to physiologically more desirable levels, thereby reducing the further secretion of gastric acids is kept to a minimum and the risk of alkalosis is avoided. With the agent obtainable according to the invention an excessive initial rise in the pH of the gastric fluids is avoided and it is a remedy for it Acidification with constant and sustained activity. Edwards describes in The Chemist and Druggist dated December 14, 1957, p.647, also the properties of an ideal remedy against acidity and states that the up to that day the closest approach to an ideal remedy was made up of moist activated alumina gel. the Edwards' views on the properties of an ideal anti-hyperacidity remedy are essentially correct .with those of Gwilt and co-workers.

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Liquid aluminum hydroxide gel is nearly ideal as an anti-acidic agent, but its liquid form makes it inconvenient to use, especially in the case of outpatients. That liquid gel. has a fairly rapid Wirlrung and has a prolonged "Action on acidity in the optimum pH range. 'Is is in terms of its properties g ^ een acidification by pepsin not significantly affected and it also loses its properties against acidosis in aging is not essential. As however, Edwards and others state it can cause moderate constipation, which has been attempted to prevent by combining the gel with other ingredients such as magnesium hydroxide or carbonate.

The benefits of a dried gel are obvious. However, the material at hand, dried aluminum hydroxide gel, is actually quite distant from it Ideal state for a remedy against acidity. It shows an undesirable delay in the rate of response with stomach acids. It does not give a longer effect against acidification at the optimal pH range and its properties against hyperacidity are strongly and adversely affected by pepsin. Also its activity against hyperacidity is lower than that of the liquid gel, since it is decreased and the one decreased by drying Activity continues to decline with aging. These weaknesses were made by Gwilt et al. and other professionals

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observed in this area.

In order to overcome the disadvantages occurring when using Moominium hydroxide as an anti-acidic agent, various mixtures of the same with other bases and basic salts were investigated in order to achieve a prolonged buffer effect within the desired p! ^r range. These mixtures include the mixture described in German patent .70.175, in which a solution of an alkali aluminate is slowly added to a solution which contains an excess of magnesium _{bicarbonate, aluminum hydroxide gel and magnesium carbonate corresponding to a composition Al 9} H ^ O-.MgCO ₇ which is washed, dried and powdered. The product contains approximately equal molar proportions of aluminum and magnesium, calculated as oxides. However, this product is quite slow to react and does not differ in this respect from dried aluminum hydroxide gel.

The product obtained according to US Pat. No. 2,797,973 by co-precipitating magnesium carbonate in the presence of an aluminum miniaturahydroxy basketonate gel was superior to that obtainable according to the German patent with regard to the acidification rate and the fermentation consumption capacity. The product described there was identified as K iuriinLununagnefllumhydroxykarbonat and it was obtained by coprecipitation at a pH of

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about ü. lis contains a relatively small amount of magnesium, namely between 5 and 2υ ';' Magnesium, calculated as MgO, at 150 parts of the total magnesium and aluminum oxides.

The aluminum magnesium hydroxycarbonate according to the US patent actually achieved a high value of the ■ Efficacy against hyperacidity not achieved by other suggested combinations. The composition is far superior to dry mixtures of aluminum hydride ur-d! '' 'ng within the optimal range of 3-5 for more than about half an hour. However shows the product in moist gel or suspension form has a tendency to thicken or harden.

Schenk proposed in Swiss Medical ./ochenschrift No. 51 p. F4 13-1420 (1954) a mixture in the ratio 3/1 of Al (OH) ₇ and Mg (OH) ₂ , which showed that it was better than aluminum hydroxide gel is alone. However, there is initially a high pH rise above 5 up to about 6 or 7, which is undesirable. i) the product according to the US patent, on the other hand, keeps the pH above 3 and never exceeds 4 »5 for times significantly longer than 2 hours.

According to US patent specification 2.880.136 and the British Patent 745,493 are aluminum hydroxide and magnesium and / or calcium carbonates at a pH of

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about 8.5 failed together. However, it also results in this coprecipitate shows a rapid initial increase in pH more than 6 and the pH remains above the maximum of 5 for more than an hour.

US Pat. No. 2,958,626 describes a process for the preparation of an anti-acidic agent, in which ITatr.lumaluminate is reacted with magnesium bicarbonate and carbon dioxide. The product of this reaction is the aluminum magnesium hydroxycarbonate according to US Pat. No. 2,797,978. An analysis of the product obtained according to the examples of US Pat. No. 2,953,626 confirms that the Procu-ct is amorphous, showing no X-ray diffraction spectra, according to infrared analysis Mixture of the above chemicals corresponds and approximately the same approximate Al ₂ O, -, MgO, Ha ₂ O and CO ₂ ~ content, pH value and capacity of the acid consumption s as the product according to US Pat . No. 2,797,978 has. It also works as if it were the same remedy for acidity in the Holbert, Noble and Grote tests.

Because of its low magnesium oxide content, the aluminum has magnesium hydroxycarbonate according to the US patent 2,797,973 have little or no laxative activity. This is disadvantageous because a laxative activity is desirable in order to counteract the clogging effect of the alurainium hydroxide

to arrive. i-! r. however, was previously not possible a

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• It is possible to produce acidification with a high magnesium oxide content, which does not result in a rapid and excessive initial pH increase above the permissible value of?, Because of the high "mcalinity of the magnesium oxide. r> as Al (Or)., - Mg (OH) ^ mixture according to FS patent 2,953,626 is an example of the effect of magnesium oxide. iig (OH) p-MgCO 7-S :, ^r stems also have a high pH value; even a mixture in the ratio 1: 3 has a pH value of 10.4.

Another problem that has arisen with the anti-acidification systems used to date, especially those that contain aluminum hydroxide gel, is based on the tendency to adsorb or occlude sodium and other foreign salts, which are the by-products of the reaction through which the anti-acidification precipitates were formed. Even the product according to US Pat. No. 2,797,878 can contain up to $ 2 sodium due to this effect. This poses a problem with patients on a low sodium or low salt diet.

Aqueous gels and suspensions effective against acidification show the further difficulty of thickening and curing during storage and for this reason pulser or similar solid systems are preferred. It actually was possible, stable aqueous systems only with the aid

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would take from auxiliary additives, such as polyhydric alcohols (US patents 2,755,220 and 2,999,790), but these systems are not entirely satisfactory either. A system that is sufficiently stable in the absence of such auxiliary additives has not yet been available.

The composition which is effective against hyperacidity and which can be obtained according to the invention has an exceptionally high level Magnesium content, calculated as oxide, but probably present as a complex carbonate, shows a great deal low salt content and rapid effectiveness, ns remains above a pH value of 3, but without one pH to exceed .7ert of 5 for at least one hour and up to 2 hours and above. Aqueous systems from serving compositions are opposed to thickening and Hardening exceptionally stable. Calcium can be used in place of the ge s; below or a part of the magnesium are used, with an equivalent effectiveness against over-acidification with- "üohalt ^ n will.

The ones available according to the invention against acidification effective means can be formerly. sch al3 magnesium and / or Calcium aluminum hydroxocarbon, .t denotes, but is among them not to pretend that they represent a single chemical compound, since the composition and structure are up is not known now. The anti-acidic agent is certainly not just a mixture of

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Aluminum trihydroxide gel and magnesium or calcium carbonate, as they do not exhibit any of the properties of such a mixture. sn irri, nuch no mixture of Oa (OH) .- ,, Mg (OIi) ₂ Al (OII), since the presence of CaO, MgO, Oa (OlO ₂ or bi.s jotz ', was not determined and its activity Against acidification is such that it indicates the absence of GnO, MgO, ¹ Ia (O ¹ T) ο or Ifg (0 ^r ) _o The aluminum, magnesium and / or calcium and carbonate and hydroxyl groups can in any "'Όπα of a complex tone or as a coordination complex :: be bound.

This agent is effective against acidification and is fully characterized by ¹ % taf-neoium- or calcium-lurain-jurahydroxy carbonate, has a ρΙί-1 / ert in an aqueous slurry or suspension of about 7 to about and a molecular ratio of Al ₉ O,.: MO of 4: i to i: iO, when M denotes magnesium and / or calcium.

These agents, which are effective against acidification, are suitable, as can be seen in the test method according to Holbert, Noble and Grote found a pH in the stomach to be within the range of 3 to 5, and preferably from 3 »5 to 4,? for two hours and longer and maintain the p "-f value to increase rapidly to a value within this TV range without exceeding the maximum optimal pH value of 5

-.11-

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The effectiveness against overacidification of the anti-overacidification agents obtainable according to the invention was determined by the methods of ITolbert, Johle and Grote, Journal of the American Pharmaceutical Association (Scientific Edition), 36, 149 (1947); 17: 292 (1943); £ 1,561 (1952) as modified by Stewart !!. Beckman, £ 9, '') ' (1960). In this method, a test sample of the anti-acidification agent is added to 150 ml of an artificial gastric fluid made from 0.0516 N-, ^c hydrochloric acid with a content of 2 g of pepsin. The artificial gastric juice is maintained at a temperature of 37.5 ⁰ C. The test procedure is carried out by continuously introducing fresh artificial gastric juice, beginning with the tenth minute of the test period, and removing the mixture of anti-acidic agent and gastric juice by overflow at a rate of 2 ml / minute. The effectiveness against acidification is determined by measuring the pH of the artificial gastric juice during the test period, which is 2 hours or longer. This test procedure was used in the examples.

The previous anti-acidic agents containing aluminum and magnesium had a pH value of 8 to 11, depending on the ratio of aluminum to magnesium. The high alkalinity of those previously produced Geenühor acidification of effective preparations resulted

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an undesirable initial increase in pH above 5, as already stated above. The obtainable according to the invention Agents effective against acidification with a pH of the suspension in water of 7 to 9 show this Effect not. Due to the lack of this effect, those obtainable according to the invention can be effective against hyperacidity Means have an exceptionally high ratio of magnesium and / or calcium to aluminum.

The ratios of aluminum to magnesium or halide are given in the form of the molecular ratio Al ₂ O ^: MO, where H has the meaning of Mg or Ca, or a mixture thereof, then AlpO .: MgO or AlpO: OaO. The anti-acidification agents obtainable according to the invention can have a ratio, calculated as the corresponding equivalent oxides, "within the range from about 4: 1 to about 1:10, without an undesirably rapid pH increase to a value above 5 subsequently There is no upper limit on the ratio of aluminum to calcium or magnesium except for those set by the acid neutralizing capacity and the pH of the final product. A preferred relatively high ratio of magnesium to aluminum, in which an anti-acidic agent with a laxative effect counteracts possible constipation effects due to the alurainiurahydroxydes,

BATH ORIGINAL

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is around 5: 3.

According to the invention, they are effective against acidification liittel by common precipitation from a common Solution made, which magnesium and / or calcium, aluminum and hydroxide ions and favorably foal dioxide contains or if carbon dioxide is not present, then will carbonized. These clays can come from any source, provided that the ρϊϊ value during the co-precipitation in the absence of carbon dioxide within the range between about 9 and about ίο and maintained at a level in the range of about 6 to about 10 in the presence of carbon dioxide, flat ended With co-precipitation, the pH is no longer critical and it can get to any level. If Carbon dioxide is absent, it can fall, but it usually rises to about 10 to about 10.5 and dLes is advantageous to ensure complete precipitation of the magnesium.

The temperature at which the coprecipitation takes place is not critical. Bequeraerweise room temperature is applied and temperatures bit to 65 ⁰ C were used to good effect. Higher temperatures can also be used if the reaction time is shortened accordingly.

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After the implementation has ended, the solution can be quenched which contributes to the total co-precipitation. It can also be aged during a period of time, again and to ensure complete joint precipitation likewise also to the complex formation of the constituents under Formation of the fu'findur.gs according to available against hyperacidity effective means to complete. Min during one Hour-aged coprecipitate is superior in terms of activity to a freshly precipitated, which is together with the change in pH with aging suggests that, although initially the co-precipitation may be terminated the reactions responsible for the formation of the complex need not yet be.

Carbon dioxide becomes with the coprecipitate either simultaneously during its formation, if carbon dioxide becomes too is present at this point in time, or after the co-precipitation has either partially or completely expired, implemented by adding carbon dioxide after co-precipitation or after aging. If carbon dioxide during the common precipitation or aging is implemented, the pH will be within the range between about 6 and about 11 held. When the carbon dioxide reacted after aging the carbon dioxide is in the reaction suspension is introduced until the pH of the slurry is reduced to between about 6 and about 7 »5.

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The reaction with the carbon dioxide usually takes one hour. Carbon dioxide is the preferred gas Source of carbon dioxide, but a solution of carbon dioxide in water can also be used. By the lo ^ lendioxyd the result is a coprecipitate with a reduced pH value and no noticeable tendency to occlude of foreign ions, such as sodium or sulfate ions. The agent that is effective against over-acidification is then separated off and taken with Washed water to remove salts.

The product can be used as a wet gel or as a slurry, which do not thicken on aging, are marketed for use in the form of suspensions or it can be spray dried or vacuum filtered to a dry cow which turns into a powder is crushed. The powder can be sold as such or in tablet form, with the usual excipients for example a polyol, a sweetener and a lubricant, for example mannitol, dextrose and magnesium stearate to be needed.

Although different methods of bringing together aluminum, magnesium and / or calcium and hydroxide ions can be used to achieve coprecipitation under the specified conditions, it is preferred to use a solution of an alkali aluminate, for example sodium or potassium aluminate and a solution

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a water-soluble calcium and / or magnesium salt, for example of chloride, bromide, iodide or nitrate, to mix n. The pH of these solutions is determined by dilute alkali, for example sodium or potassium hydroxide or carbonate adjusted to the pH during coprecipitation within the range between about 9 and hold about 10. If it is important that the anti-acidic agent is free of sodium or potassium ions sodium or potassium hydroxide should not be used with calcium-containing anti-acid agents because of the strong tendency to form strongly alkaline calcium coprecipitates. This occurs with magnesium-containing Remedies against acidity do not appear.

The two solutions in the approximate stoichiometric Proportions to give the desired composition of the anti-acidic agent are then made by mixing mixed with water and then left to react, forming the coprecipitate. In the implementation The salts of the alkali metal, the aluminate and the anion of the magnesium and / or calcium salt are formed as by-products. These are soluble and do not precipitate. They can be easily washed out of the coprecipitate, which is not Shows a tendency to occlude such salts on separation from the reaction mixture.

The following examples serve to further illustrate the invention and represent preferred embodiments

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Forms.

Examples 1 to 6

Ss became an aluminum-magnesium-hydroxy-carbonate prepared in which 226.3 g of sodium aluminate in 3460 g of deionized Water, which with 330 g of a 50% sodium hydroxide solution was mixed, were dissolved and 356 g of magnesium chloride hexahydrate Were dissolved in 4580 g of deionized water, whereupon these solutions to 4300 g deionized water at room temperature was added at such a rate and in such proportions as that the pH was kept between 9.5 and 10. It took one hour to complete the reaction. To At the end of the simultaneous addition, the pH was 9.65 and a gelatinous white precipitate was found educated.

With continued stirring, the slurry was aged for one hour. During this time the pH dropped the slurry drops to 9.5. 250 grams of carbon dioxide were then passed through the aqueous slurry with continued stirring blown at room temperature for 90 minutes during which the pH dropped to 6.1.

The slurry was left for about 2 hours » danxffiltrlert and the filter cake repeated with deionized water to remove sodium and Chloride ions. 1863 g of a combined

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obtained pressed gels in paste form.

The compressed gel showed the following analysis:

Table 1 Compressed gel

Molecular ratio Al ₂ O: MgO 1: 3.4

Cl'ions 0.1 "

Na ⁺ ions 0.07 #

GO ₂ 1.6 #

Suspension of the compressed gel in H ^ Q pH 8.0

Capacity of acid consumption 23.4 ml n / 10

HGl / g suspension

Equivalents Al ₂ O, in suspension 1.7 ^) 4 ^, based on

Equivalent MgO »» ■ »2,3« ^{the whole}

Oxides

It was found with prolonged storage that these properties were not noticeably affected and that the Gel did not thicken or harden.

488 g of the compressed gel were dried in air at 45 ° 0 for 21.5 hours to a constant weight of 116 g. The product was passed through a pfeilver toothed sieve 0.05 cm to a soft white powder

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pulverized. This powder was analyzed and the results obtained are listed in the table below.

j Table II

1: 3, 43 22.6 of 30.5 i: f 1.4 0.03 269 ml n / 10 HCl / g
powder

Molecular ratio Al ₃ O ₅ : MgO

Equi ^ stalente AIpO, in powder

Equivalents of MgO "" Cl "" i <men

Ha ⁺ ianen

Acid consumption capacity

CO ₂ , 6.4 ί>

pH (resuspension with 496 AIpO,) 7.8

"S9 showed after prolonged storage that these properties did not change.

Another part of the compressed gel was slurried in Waaetr and in a commercially available 6 meter spray dryer spray-dried with a flat bottom at an inlet temperature of 34 ° C and an outlet temperature of 93 ° 0, A soft white powder was obtained, the following Analye «. showed:

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Table III

Molecular _{ratio Al 3} O ₅ IMgO 1: 3.63

Equivalents Al ₂ O ₇ £ 22.3

Equivalents MgO £ 32.3

pH (resuspension with 4 $ Al ₉ O,) 8.2

Cl "ion £ 1.5

Na ⁺ ions 0.035 %

Capacity of acid consumption 271 ml n / 10 Hcl / g

powder

The test results according to Holbert, Hoble and Grote for these anti-acidic agents are in Table IV brought.

1363

Table IV

(Minu- pH of the artificial gastric juice

ten)

Ex.
No.

Suspension of the
compressed gels in H ^ Q

dried
gel

spray dried gel

5 ecm

10 ecm

0.445 R. 0.39 R. 0.5 R.

O 1.5 1.5 1.5 1.5 1.5 1.5 1/4 2.0 2.1 2.0 2.1 2.0 2.5 1/2 2.0 2.3 2.0 2.4 2.0 3.5 i 2.0 2.8 2.0 3.0 2.3 3.9 2 2.4 3.9 2.3 3.9 3.5 4.0 3 3.5 4.0 2.7 4.0 3.9 4.0 4th 3.9 4.0 3.7 4, I. 4.0 4.0 5 3.9 4.0 3.9 4, I. 4.0 4.1 ö 3.9 4.0 3.9 4.1 4.0 4.1 7th 3.9 4.0 3.9 4.1 4.0 3 3.9 4.0 3.9 4, I. 4.0 4! ι 9 4.0 4.1 3.9 4, I. 4.0 4.1 10 4.0 4.1 3.9 4.1 4.0 4.1 20th 3.7 4.0 3.7 4.0 3.8 4.1 30th 3.7 3.9 3.7 3.9 3.8 4.0 40 3.7 3.9 3.7 3.9 3.8 3.9 50 3.6 3.8 3.6 3.8 3.7 3.9 60 3.5 3.8 3.5 3.8 3.7 3.8 70 3.4 3.8 3.4 3.7 3.6 3.8 80 3.2 3.7 3.2 3.7 3.5 3.8 90 2.9 3.7 2.9 3.6 3.4 3.7 100 2.5 3.6 2.6 3.6 3.1 3.7 110 2.3 3.5 2.3 3.5 2.6 3.7 120 2.1 3.4 3.4 2.3 3.6 130 3.3 3.3 2.1 3.5 140 - 3.0 - 3.1 3.5 150 - 2.6 - 2.8 - 3.3 160 2.3 _ 2.5 2.8 170 2.1 - 2.3 - 2.4 180 - - 2.2 -

The values show that the compositions prepared according to the invention are effective against

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Acidification are able to maintain a pH within the range of 3 to 5 for a period of 84 to 142 Minutes to maintain. The initial time required to reach a pH between 3 and 5 was a maximum of 4 minutes and less for four of the six samples of the anti-acidic agents obtainable according to the invention than 2 minutes. Even with large doses, the initial pH did not rise to a value above 4 »5.

With equivalent dosages of the agent effective against acidification, equivalent neutralization results were obtained, regardless of whether a moist form of the slurry of the agent or a resuspension of its dried powder was used. The agents which are effective against hyperacidity and can be obtained according to the invention can consequently be administered in moist or dry form with the same effectiveness.

The spray-dried anti-acidic composition according to Examples 5 and 6 was suitable for maintaining a pH in the range from 3 to 5 for a period of about 100 to over 150 minutes.

For comparison with this anti-acidic agent available according to the present invention, various mixed aluminum hydroxide-magnesium hydroxide and aluminum hydroxycarbonate-magnesium carbonate slurries were prepared by measuring out weighed amounts of the two gels in one

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Amount of deionized water were mixed. The mixes were stirred at 1000 revolutions / minute in a "j.ightnin mixer for one hour and then were in a homogenized with hand operated homogenizer.

There were three Al (OH), - Mg (OH) ^ compositions manufactured using commercially available materials in the following way:

A. 110.5 g of a thick reactive suspension of compressed aluminum hydroxide gel were added with 72 g of a moist paste of magnesium hydroxide mixed and slurried in 418 g of deionized water.

B. 108.2 g of a thin suspension of a reactive compressed aluminaum hydroxide gel were with 72 g of a moist paste of magnesium hydroxide mixed and slurried in 420 g of deionized water.

C. 80.8 g of a highly concentrated aluminum hydroxide gel with slightly lower reactivity than the above compressed aluminum hydroxide gel were used with 72 g of a moist paste of magnesium hydroxide mixed and slurried in 447 g of deionized water.

The analysis of the above three suspensions showed in each case an AlpO ^ content of 1.86 fo _f, an MgO content of 2.5 # and a molecular ratio of AlgO ^ of 1: 3.4. The pH of the slurry of sample A was 3.15, that of sample B was 8.5 and that of sample C.

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The acid consumption capacity of these samples was 23 _t 5, 24.3 and 22.8 ml n / 10 HCl / g suspension, respectively.

The effectiveness against acidification of the above three suspensions was determined with a dose of 10 ml and is in Table VI along with Comparative Example 2 listed.

D. An aluminum hydroxide suspension was prepared on the following basis Way made:

226.8 g of sodium aluminate were dissolved in 2000 g of deionized water and carbon dioxide gas was bubbled through the solution at a rate of 0.28 m per hour until a pH of 7.3 was reached. The slurry was then aged, filtered and washed for one hour to yield 296.7 grams of a compressed gel containing 34.4 weight percent Al ₂ O. A suspension with 1.86% of AIgO was made from the above preparation, which had a pH of 7.55 and an acid consumption capacity of 0.5 ml of n / 10 HCl / g of suspension.

The anti-acidity efficacy of the above suspension was also examined and is shown in Table VI indicated under D with a dosage of 10 ml.

E. 65.8 g of this compressed gel was mixed with 146 g of magnesium hydroxide and then in 1006 g of deionized Slurried water. This mixture became a Hour in a Llghtnin-Miecher at 1000 üadrehungeiv ^ linute

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stirred and homogenized. When analyzed, this mixed gel gave the following values:

Table V

Molecular ratio Al ₂ O: MgO 1: 3.4

AIgO, - content of the suspension 1.86 #

MgO content of the suspension 2.50 #

pH 9.5

Acid consumption capacity 13.9 ml n / 10 HCl / g

suspension

The effectiveness against hyperacidity was also determined and is in Table VI under S at a dose of al included.

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Table VI

Minimum pH value of the artificial gastric juice

example

No. 2 A B C D B

0.1.5 1.5 1.5 1.5 1.5 Γ.5 1/4 2.1 1.8 4.4 2.6 <2 2.6 1/2 2.3 3.0 4.8 4.1 "5.0

1 2.8 4.7 5.7 4.4 "5.9

2 3.9 5.2 6.8 4.6 »6.4

3 4.0 5.9 7.2 4.8 "6.6

4 4.0 6.0 7.4 4.9 "6.7

5 4.0 6.0 7.5 5.1 "6.8

6 4.0 6.1 7.5 5.2 », 6.9

7 4.0 6, I 7.6 5.4 "7.0

8 4.0 6.1 7.6 5.5 ^tt 7.0

9 4.1 6.1 7.6 5.6 » 7.1 10 4.1 6.1 7.6 5.8» 7.1 20 4.0 5.3 7.2 5.7 "5, 8 30 3.9 5.0 6.8 5.4 "5.8 40 3.9 5.0 6.5 4.9" 5.7 50 3.8 4.9 6.2 4.5 ⁿ 5 .7 60 3.8 4.8 5.8 4.2 »5.6 70 3.8 4.7 5.2 4.1" 5.4 80 3.7 4.6 4.6 4.1 " 5.3 90 3.7 4.5 4.3 4.0 " 4.8

100 3.6 4.3 4.1 4.0 »3.2

110 3.5 3.5 3.9 3.8 = * 2.8

120 3.4 2.7 3.1 3.2 "2.5 130 3.3 2.5 -
140 3.0

The values listed in Table VI are graphical Shown in Figure 1.

Mixed known ÖIE manufactured th when comparing the Säureneutralisiereigenechaf as indicated above, old product naoh Example 2 shows that the mixed SEIE A, B, 0 and B is a tendency sur "On neutral is ation" beiges, when products D came the pH

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never above 2. All failed to keep the pH of the artificial gastric juice within the desired range to hold for as long a period of time as the anti-acidification agent obtainable according to the invention.

Am part of all the slurries of the samples A, B and 0 were in air at 45 ⁰ C in a furnace with Luftkreislt | a.fführung dried for 32, 27.5 and 23.5 hours and pulverized to obtain a herringbone screen of 0, 05 cm was used to give a soft white powder.

The acidity efficacy of the three powders was determined using a dosage of 1 g and the results are as follows in comparison with the comparative example 4 listed.

65.8 g of the compressed gel E was mixed with 146 g of magnesium hydroxide and slurried in 1006 g of deionized water. This mixture was then stirred for one hour at 1000 rpm using a Lightnin mixer. 680.6 g of this slurry was dried at 45 ⁰ G in an oven with air circulation during 27.5 hours, whereby a cake yielded formed by a herringbone sieve of 0.05 cm to 49.6 g of a white powder was pulverized.

The effectiveness against acidification of the dried powder was determined and is shown in Table VTI under S. listed at a dosage of 1 g.

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Time
tilin
ten)

Table VTT

p "-. v ^r ert of artificial loading: ¹ , ftes

example

TJ

i / 4 i / 2

2
3
4th
5
6th
7th
8th
9

10

20th

30th

40

50

60

70

30th

90

■ iOO

110

120

130

140

150

160

1.5
2 ,,

2.4

3.0

3.0

4.0

4, i

4, i

4, i

4, i

4.1

4, i

4.1

4.0

3.9

3.9

3.8

3.8

3.7

3.7

3.6

3.6

3.5

3.4

3.3

3, i

2.8

2.5

1.5 2, i 2.3 3.7 4.7 5.0 5.2 5.4 5.5 5.6 5.7 5.8 5.8 5.0 5.0 4.9 4, 8 4.6 4.5 4.3 '4.2

4.1 3.9 3.7 3.5 3.2 3.0 2.7

'j , 5 ι , 5 O
<- 1 , 2 2 , 2 2, ,8th , υ 4, , 3 4th , 6 4th
H , 17th , 0 5, O ο
, ^ 5, 3 5 , 3 5, 5 5 , 5 5, 6th 5 , 5 5, 7th 5 , 6 5, 8th 5 , 6 5, 8th , 7 5, 9 5 , 7 5, O 4th , 9 5, 9 4th ,8th 4, 7th 4th , 7 4, 6th 4th , 4 4, 5 4th , 3 4, 4th 4th ,1 4, 3 3 , 9 4, 2 , 6 4, I. 3 , 6 3, 9 , 3 3, ό 3 , 6 3, 3 3 , 4 3, O , ι 2, 8th 2 , 3 2, 6th • τ
L- , 6

1.5 3 »S3

5, i

6.0

6.5

6.7

6.9

7.0

7.0

7.1

7.1

7.2

7.2

6.0

5.3

5.7

5 _f 6

5.4

5.0

4.4

3.7

3.5

3.4

3.1

3.0

2.9

2.9

2.3

D ^r e values of Table VII are presented graphically in FIG. 2

From the above values it follows that the
Dried powder made from the mixed gel tends to "over-neutralize", with an increase above 5
results in half an hour and that the pH

- 29 -

909813/1363

remains within the desired range only during the last two hours of the 160 minute trial period.

It follows that the manufactured according to 3 of the invention Powdered agents that are effective against acidification are significantly different from merely mixed gels, since the undesirable over-neutralization properties of the Magnesium hydroxydes in those obtainable according to the invention are effectively masked against (acidifying agents.

Example 7

226.3 g of sodium aluminate were in 2000 g of deionized Water, which with 990 g of a 50 'strength sodium hydroxide solution was mixed, dissolved. 1550 g magnesium chloride hexahydrate were dissolved in 3000 g of deionized water. These solutions simultaneously became 4,500 grams of deionized water from room temperature over 58 minutes at such a rate and in such proportions that the pH was maintained between 9.5 and 10. It made up a gelatinous white precipitate forms. After the final portions of the solutions were added, the slurry became Aged for an hour during which time the pH value rose to 1 1/2. By blowing in 639 g of carbon dioxide gas the slurry for 100 minutes adjusted the pH to 7.4. The slurry then became

909813/1363

Aged for one hour after which it was filtered and the filter cake washed with deionized water. 2450 g of a compressed gel was obtained in paste form. "Oine aqueous suspension was prepared from the above compressed ± Ge and corresponded to an approximate 4.1-0, .- content of i, Z B and a HgO content of ■ - showed r'uspenslon> Diope. ','?. '. following analysis:

Table VIII

Molecular ratio AIpO,: MgO equivalents Al ₀ O-, in the suspension equivalents MgO in the suspension

Cl "ions

Na ⁺ ions

Acid consumption capacity

i: 5.9 , β 5 x; 4.2 55 8.8

0.07 '/ <0.07 Γ'

31.1 ml η / 10 HCl / g suspension

2.2 ϊ> (in the compressed gel)

T3 ± ne sample of 491.8 g of the compressed gel was dried at 45 ° C. in air for 23 hours to a constant weight of 147.0 g and then it was pulverized through an arrow-shaped sieve of 0.05 cm which white powder obtained. This powder showed the following analysis:

- 3.1 BAD ORi

909813/1363

Table Ιλ

Molecular ratio Al ₂ O.: MgO 1: S, 9

ΛΙρΟ. -Equivalents ι "'j . 3 ': '<

MgO equivalents 32, i; "'.

Cl ~ ions 0 ^,! i '/'>

Na ⁺ ions <0.07

0O ₂ - 7.35

The properties of the powder against acidification have been determined and are listed in the following table:

909813/1363

Table X

(Minutes) pH of the artificial gastric juice

0.5 g 1.0 g

0 1.5 1.5

ι / 4 2.6 4.1

ι / 2 4.0 4.3

-i 4.2 4.4

2 4.2 4.5

3 4.2 4.6

4 4.2 4.7

5 4.2 4.8

6 4.3 4.9

7 4.3 5.0

8 4.3 5.1

9 ■ 4.3 5.2 10 4.5 5.3 20 4.0 4.9

30 4.0 4.6

40 3.9 4.3

50. 3.8 4.1

60 3.7 4.1

70. 3.4 4.0

80 3.1 3.9

90 2.8 3.9

100 2.6 3.8

110 2.4 3.6

120 2.2 3.5

130-3.3

140 - 3.0

150 - 2.7

160 - 2.5

170 - 2.3

This anti-acidic agent was capable of maintaining a pH in the range of 3 to 5 for a period of time Between 79 and 130 minutes of the test period. The one to achieve a pH value within The time required for this range was only 10 seconds or 19 seconds. The means according to this example

909813/1363

^"M did not seriously over-neutralize, although the AlpO: MgO ratio was very high. The pH only exceeded 5 for a period of three minutes.

Example 3 '

226.3 g of sodium aluminumate are dissolved in 4700 g of deionized V / ater, which contained 607 g of sodium carbonate, dissolved. 856 g of magnesia chloride hexahydrate were in 2000 g of deionized V / ater resolved. The two solutions became 5500 grams of deionized water over an eighty period Ilinuten at such a speed and in such proportions added to keep the pH between 9> 5 and OK. The pH at the end of the addition was 9.5. The slurry was then aged for an hour, during which time the pH dropped to 9.45. Then i30 g Carbon dioxide gas was blown through for 60 minutes, whereupon the pH was 8.5 and the slurry was then 2 hours aged long. The slurry was filtered and the Filter cake washed with deionized water. 1900 g of a compressed gel were obtained.

An aqueous suspension of the above compressed gel was prepared with an Al ₂ O, content of approximately 1.8%. This suspension showed the following analysis:

- 34 -

809813/1363

Table XI

Molecular _{ratio Al 2} O ₃ -TIgO 1: 4.05 ΑΙρΟ -, - content of the suspension i, 87 ^r / ·

MgO content of the suspension 3.00 '·'

pH 7.95

Cl "ions 0.0 1 >&

Na ⁺ ions 0.07 '/>

Acid neutralization capacity 24.7 ml n / 10 HGl / g

suspension

CO ₀ 4.38>. '(In total

^J 2

pressed gel)

The effectiveness against acidification was determined and is listed in the table below.

909813/1363

Table XII

(Minutes) pH of the artificial hag sap

5 cc dosage

0 1.5 1/4 3.7 1/2 3.9

1 Ί, Ι

2 4.3

3 4.3

4 2 »3

5 4.4

6 4.4

7 4.4

8 4.4

9 4.4 10 4.5 20 · <4.2 30 4.1 40 4.0 50 3.9 60 3.8 70 3.7 30 3.5 90 3.2

ι OO 2.9

110 2.6

120 2.3

130 2, Ί

The agent, which was effective against over-acidification, increased the pH value of the artificial gastric juice within 10 seconds after the addition to 3.0. However, this "over-neutralized" it The stomach acidity does not mean that never exceeds one pH value of 4.4 rose. The gastric acidity was within the desired range of 3 to 5 for 90 minutes held.

- 36 909813/1363

Example 9

^ s became an aluminum-magnesium-calcium-hydroxy-earbonate produced with effectiveness against acidity according to the invention in the following way:

226.8 g of sodium alurainate were dissolved in 2000 g of deionized water to which 440 g of a 50% sodium hydroxide solution had been added. 856 grams of magnesium chloride hexahydrate and 1180 grams of calcium chloride hexahydrate were dissolved in 2000 grams of deionized water. These solutions were added together to 5500 grams of deionized water over a period of 67 minutes at such a rate and proportions as to bring the pH between 9.5 and 10
hold on, admittedly. When the addition was complete, the pH was 9.8 and the slurry was aged for 60 minutes; during this time the pH rose to 10.05.
The pH of the aged slurry was then adjusted to 6.0 by bubbling 297 grams of carbon dioxide gas through the slurry over a period of 63 minutes. The slurry was aged for two hours, filtered and the filter cake washed with deionized water. 2482 g of a compressed gel was obtained. An aqueous slurry of the same showed the following analysis:

- 37 -

909813/1363

- 37 Table XIII

Molecular _{ratio Al 2} O ₅ : MgO Molecular _{ratio Al 2} O ₅ ICaO equivalents AlpO-, in the suspension equivalents MgO in the suspension equivalents CaO in the suspension

Cl ~ ions

lla ⁺ ions

Acid consumption capacity

1: 3.56 1: 0, όι 1.9 '> 2.58 "/ ο 0.64 7 ° 0.95 0, ι', S £ 0.07 $

25.3 ml η / iO HCl / g suspension

2.2 % (in the compressed gel;

474.9 g of the compressed gel were ^{dried in air at 45 °} C. for 19 hours to a constant weight of 02.9 g.

ilach Pul. he 13 ie rung ciurcla an arrow-toothed sieve of h, ') ^r ) cm resulted in a soft, white i ^: powder with the following analysis:

Table XIV

Molecular ratio Al ₂ O ₅ : MgO Molecular _{ratio Al 0} O.,: CaO Al ₂ O, content of the powder KgO content of the powder CaO-C content of the powder 1: 3.54 1: 0.62 19.5 $ 27 , 4 % 6.55 #

909813/1363 - 38 -

pH (resuspension rait 4 $ AIpO ^) 8.95

Cl "ions i, 33 $>

Na ⁺ ions <£ 0.07 #

0O ₂ 10.3 1>.

The anti-acidity efficacy was determined and the results are shown in Table XV.

_BATH

909813/1 ^ 363

- 39 -

Table XV

pH of the artificial gastric juice

Suspension in H ₀ O 10 ecm dried gel 5 ecm 1.5 0.5 r ι £ O - |, 5 3.9 '', 5 1.5 i / 4 2.0 4.1 2.1 2.5 1/2 2.2 4.2 2.3 3.0 1 2.8 4.3 2.6 4.1 2 4.0 4.4 3.9 4.3 3 4.0 4.5 4.1 4.4 4th 4.0 4.5 4.1 4.4 5 4.0 4.6 4.1 4.5 6th 4.1 4.7 4.2 4.5 7th 4.1 4.7 4.2 4.6 8th 4.1 4.8 4.2 4.6 9 4.1 4.8 4.2 4.7 10 4.1 . 4.6 4.2 4.7 20th 3.9 4.4 3.9 4.5 30th 3.3 4.2 3.9 4.4 40 3.8 4.1 3.3 4.2 50 3.7 3.9 3.7 4.1 60 3.7 3.9 3.6 4.0 70 3.6 3.8 3.5 3.0 8ü 3.4 3.8 3.3 3.9 90 3.2 3.7 3.1 3.8 ■ 100 3.7 3.8 110 - 3.6 - 3.7 120 - 3.5 - 3.6 130 - 3.4 _ 3.6 140 - 3.2 - 3.5 150 - - 3.5 160 - - _ 3.4 170 - - 3.3 130 - - - 3.3 190 - - - 3.1 200 - - 3.0

With this remedy against over-acidification, the pH value of the artificial gastric juices is effectively maintained between 3 and 5 "for up to 200 minutes. Pas remedy in form

of a stable dry powder had a particularly high

- 40 -

909813/13 6 3

and ongoing activity against hyperacidity. The pH of the artificial gastric juices was set to a value between 3 and 5 within half a minute after adding the agent B. and held there for 200 minutes and the pH became within the preferred range of 3.5 held up to 4.5 for 45 minutes of the test search. Although this anti-acidic agent shows rapid and long-term effectiveness, it "over-neutralizes" them normal acidity of the stomach no.

Example 10

113.4 g sodium aluminate in 195 g of a 50 'follow Natr iumliydroxydlö solution and dissolved 1000 g of deionized water. 32 grams of magnesium chloride hexahydrate was dissolved in 75 grams of deionized water. These two solutions were added simultaneously to 2,750 grams of deionized water at such a rate and in proportions as to maintain the pH between 915 and 10.

After all the aluminate solution has been added there was a significant amount of the magnesium chloride solution left. To keep the pH between 9.5 and IO continued The remaining part of the alurainate solution became to maintain it added while carbon dioxide gas f through the solution at a speed of 0.056 m / h. was blown. The final pH was 10.1.

- 41 909813/1363

The slurry was then aged, increasing the pH to 10.4. 280 g of carbon dioxide gas were used Adjustment of pH to 7.7 over one hour used, whereupon the slurry aged 2 hours, filtered and the filter cake was washed, showing an aqueous suspension made from the compressed gel following analysis:

Table XVI 3.29: Molecular ratio Al ₂ O.,: MgO 3.99 Ά ΑΙρΟ -, - content of the suspension £ 0.43 MgO content of the suspension 7.35 pH 0, Oi ^C L 01 ~ "ions <0.07; ' Na ⁺ ions 10.45 Acid consumption capacity

^jKß 2

suspension

, 28 ^ / i (in the compressed Gel)

The acidity efficacy of the above composition was determined. The agent kept the pH of artificial gastric juices within the desired range of 3 to ¹⁵ for more than an hour without "over-neutralizing".

909813/1363

Example 1 i .

Aluminum calcium hydroxy carbonate was prepared from a solution of 1,13.4 g sodium alurainate, dissolved in 1,500 g deionized water mixed with 193.5 g sodium carbonate, and from a solution of 590 g calcium chloride hydroxahydra. t made in 100 g of deionized water. These "two solutions were added together to 2250 g of water in the course of ^r yj ilinutes, while the pH value was kept between 9.5 and OK. After aging for one hour, the pii-tfert rose to ΊΟ, ίρ, whereupon! 50 g of carbon dioxide gas were blown through the slurry to adjust the p ^T : "- '. Fertes on!;,; ■ within an hour. The slurry was then aged an additional two hours, filtered and the filter cake washed with deionized water. 1,103 g of compressed gel was obtained.

An aqueous suspension prepared from the above compressed gel showed the following analysis:

Table XVII 1: 4.36 Molecular ratio Al ₂ O ₃ : CaO 1.31; / Al ₂ O, content 4; O4 "'· CaO content 7.8 pH 0.00? Ci "ions 0.025 Na ⁺ ions

Acid neutralization capacity 19.7 ml n / 10 HGl / g

suspension

9.3 .. '■ (in the compressed gel)

90Ö813 / 1363

The Alurainium-Ealζium-Hydroxy-Carbonat with effectiveness against acidification kept the pH value of artificial gastric juices within a range of 3 to 5 for two hours without "over-neutralizing ^M.

Example 12

An aluminum magnesium hydroxy carbonate was prepared according to the invention by dissolving 56.8 grams of sodium aluminate in 500 grams of deionized water mixed with 97.5 grams of a 50% liatriura hydroxide solution and adding 214 grams of magnesium chloride hexahydrate these solutions were dissolved in 500 g deionized water, heated to 65 ° C and then at the same time, these solutions were added to 1375 g of deionized water also of 65 ⁰ C at such a rate and in such proportions that the pH value between 9.5 and 10 was maintained and the temperature remained at 62 to 65 ⁰ C. It took one hour to complete the implementation. After the simultaneous addition was complete, the pH was 9.65 and a gelatinous white precipitate had formed.

The slurry was brought to room temperature and aged with continued stirring for one hour. 167 g of carbon dioxide gas was then bubbled through the slurry with continued stirring at room temperature for 60 minutes, the pH dropping to 8.0.

909813/1363

The slurry was aged for about 2 hours, filtered and the filter cake repeatedly with deionized Washed water to remove sodium and chloride ions. 651 g of compressed gel was obtained in paste form.

A stable aqueous suspension with an approximate AlpO ~ content of 1.8 % was produced from the compressed gel:

Table VIII Suspension of the compressed gel in HpO

Al ₂ O ₃ ' $ 1.79

MgO 2.38 io

Molecular _{ratio Al 2} CyMgO 1: 3.37

Cl ions 0.017 %

Na ⁺ ions 0.07 #

pH 8.2

Capacity of acid consumption 22.1 ml n / 10 HCl / g

suspension

CO ₂ £ 0.8

On prolonged storage it was found that these properties were not noticeably affected.

357.8 g of the compressed gel were ^{dried in air at 45 °} C. for 22.5 hours to a constant weight of 58.7 g. The product passed through a 0.05 cm herringbone screen to a soft white powder

- 45 909613/1363

pulverized. This powder was analyzed and gave the following values:

Table XIX

Molecular _{ratio Al 2} O ₅ ZMgO 1: 3.37

Equivalents of Al ₂ O ₅ in the powder 23.5 t

MgO 31.2 '·'>

Cl ~ ions 0.2 .1

Ha ⁺ ions less than 0.07 '/>

Acid consumption capacity 290 ml n / 10 HCl / g

powder

CO ₂ 10 /.

pH (resuspension with 4? »

Al ₂ O ₅ ) 7.5

On prolonged storage it was found that this Properties were not changed. The trial values after Holbert, Noble and Grote for these anti-acidic agents are listed in Table XX.

- 46 -

909813/1363

Table XX

Time

(Minutes) pH-Y / ert of the artificial gastric juice

Suspension of the compressed gel in H _? 0

IO ecm

dried G gel 5 I. 1 i, 2 2, 45 2, 0 2, 0 3, 2 4, 25th 4, 25th 4, 25th 4, 3 4, 35 4, 35 4, 2 4, 1 4, 0 4, 9 4, 3? 5 » 3 3, 7th 3, 7th 3, 65 3, ό 5, 5 'y , 45 3, 35 5, 3 3, 25th 3, ^: 5 3, 0 3, 3,

0 1.5 1/4 2, i 1/2 2.4

1 ■ 2.8

2 3.9

3 4, ü

4 4, ι

5 4, I.

6 4, i

7 4 ,.

8 4, · 5

9 4.15 OK 4.15

20 4.15

30 4.0

40 4.0

50 3.45

60 5.9

70 5.85

80 5.35

90 5.8

100 3.75

IO 3.7

12U 5.6

i30 5.4

140 5.2

I50 2.8

160 2.6 170
180

These values show that &a; 3 these anti-acidic compositions are suitable, maintain a pH in the range of 5 to 5 for a period of 150 to 130 minutes. The initially time required to reach a pH value between 3 and 5

909813/1363 - 47 -

enough, was a maximum of 2 minutes. Even in large doses, the anti-acidic agents increased the initial one pH value not above 4 »35.

The agent effective against acidification gave equivalent neutralization results at the dosages, quite whether a wet form of the slurry or a resuspension of the dried powder was used. As a result, the acidic agent can be used with equal effectiveness in wet or dry form administered.

Example 13

75.6 g of sodium aluminate were dissolved in 667 g of deinized water with 152.3 g of sodium hydroxide flakes. 285.3 grams of magnesium chloride hexahydrate was dissolved in 667 grams of deionized water. These solutions were heated to 65 ⁰ C and added simultaneously to 1500 g of deionized water also of 65 ⁰ C with 82 ig carbon dioxide gas with such a velocity and such proportions that the pH-value between 9 »0 and 10 in the course of 45 minutes, remained while the temperature between 65 and 70 ⁰ O was kept. A gelatinous white precipitate formed. Hach addition of the last parts of the solutions, the slurry in 10 minutes, brought to 25 ⁰ C, filtered and the filter cake washed with deionized water. 649 E äes compressed gel obtained in paste form.

909813/1363 - 48 -

U67253

A stable aqueous suspension was prepared from the above compressed gel, which corresponds _{approximately to an Al 2} O, content of 1.8 %. This suspension showed the following analysis!

Table XXI

Molecular ratio Al ₂ O ₅ : MgO equivalents Al ₂ O, in the suspension equivalents MgO in the suspension

Cl "" ions Na ⁺ inside

Acid consumption capacity

1: 3.94 2.03 + 3.16 # 8.7

0.008 "i 0.002 io

27.3 ml n / 10 HCl / g suspension

$ 0.78) - (in compressed gel)

100 g of the compressed gel was at 45 ° C for 6.75 hours to a constant weight of 26.4 g dried in air and pulverized through an arrow-toothed sieve 0.05 cm to a soft white powder. This powder showed the following analysis:

Table XXII 1: 3.94 Molecular ratio Al ₂ O,: MgO 21.8 0 Al ₂ O equivalent £ 34.0 MgO equivalent 0.04 # Cl ~ ions 0.02 % Na ⁺ ions 8.4 9i CO ₂ 283 ml n / 10 HCl / g Capacity that consumes acid 8.0 pH (4 # Al ₂ O ₅ slurry)

909813/1363

- 49 -

ORDINAL

The effectiveness of the gel and PiJyers against acidity have been determined and are listed below:

Table XXIII

Time pH of the artificial Gastric juice (Minutes) Suspension of the together dried pressed gels in H ₂ O gel 1.8 1.8 O 3.4 2.7 ■ '/ 4 4.2 4.0 1/2 4.25 4.3 I. 4.5 4.5 2 4.5 4.6 3 4.6 4.55 4th 4.65 4.7 5 4.7 4.7 6th 4.7 4.75 7th 4.7 4.75 8th 4.7 4.8 9 4.75 4.8 10 4.7 4.7 20th 4.7 4.65 30th 4.6 4.6 40 4.5 4.55 51 4.5 4.45 60 4.45 4.40 70 4.45 4.3 80 4.4 4.2 90 4.35 4.1 100 4.3 4.0 . 10 4.25 3.95 20th 4.25 3.8 30th 4.15 3.5 i40 4.1 3.1 , 50 4.0 2.85 ,SO 3.85 2.65 170 3.7 - 130 3.3 - 90 3.0 -

- 50 909913/1363

This anti-acidification agent was capable of maintaining a pH in the range between 3 and 5 for a period of 150 to 200 minutes. The time required to reach a pH value within this range was only 1/4 to 1/2 minute. The agent effective against acidification did not "over-neutralize", although the ratio AIgO. *: MgO was very high.

The compositions which are effective against acidification and which can be obtained according to the invention have been found to be more effective than simple ones Mixtures of their ingredients. It is unusual and unexpected that a co-precipitated G-el or corresponding slurry is obtained, which is more reactive than a simple Geraisch of the components. Magnesium hydroxide itself is characterized by a high initial increase in pH with inevitable "over-neutralization". This undesirable property of the magnesium hydroxide is in the compositions obtainable according to the invention masked with effectiveness against over-neutralization while maintaining its desired laxative property remains to counteract the clogging effects of aluminum hydroxide. Though the dried gel of aluminum hydroxide shows a delay and a decrease in its activity against hyperacidity, there is no prolonged one Effect against acidification and is adversely affected by pepsin, while the agents available according to the invention

- ⁵ H-

909813/136 3

show no such loss of acidic activity on drying. They also retain their effectiveness Aging at. The proportion of magnesium present in the agents obtainable according to the invention can be much greater, than it can be explained by adsorption or absorption. The agents obtainable according to the invention also show with effectiveness against acidification a great resistance to the inclusion of foreign ions.

The evolution of gas during the neutralization reaction of an anti-acidic agent is undesirable. Fuchs describes in p. 40 line 22 Drug & Cosmetic Industry, 64, 692 (1949) "that some soluble bicarbonates during the neutralization reaction. release carbon dioxide gas almost instantaneously, and he notes that this is an undesirable property for an anti-acidic agent. The anti-acidification agents obtainable according to the invention do not release large amounts of gas during the period of acid neutralization and buffering, in contrast to many known anti-acidification agents. The compositions obtainable according to the invention with effectiveness against acidification have a maximum CO ₂ content of only about 5-6 percent by weight of the compressed gel and the C0 ₂ complex bond is of such a type that there is no sudden and voluminous development of gas.

- 52 -

909813/1363

The compositions obtainable according to the invention with effectiveness against over-acidification are stable and retain their neutralizing and buffering effectiveness during a period whether they are stored as a moist gel or slurry or in the form of a dry powder will. Many of the known anti-acidic agents are unstable and can be used as wet gels or suspensions not be stored.

- Claim: -

909813/1363

Claims (1)

Claim; Process for the production of an agent against gastric hyperacidity using aluminum and magnesium by joint precipitation from an aqueous solution, the metals being present in ratios of 4: 1 to _{1:10, based on the weight of Al 2 CU: MgO, characterized} that the goprecipitate is precipitated from an aqueous solution having a pH between about 9 and about 10 and the reaction is terminated by introducing an amount of carbon dioxide sufficient to maintain the pH between about 6 and about 10. 909813/1363