WO1999035088A1 - Carbonate basique de magnesium et d'aluminium, son procede de fabrication et son utilisation comme composition pharmaceutique destinee au traitement de l'acidite gastrique - Google Patents

Carbonate basique de magnesium et d'aluminium, son procede de fabrication et son utilisation comme composition pharmaceutique destinee au traitement de l'acidite gastrique Download PDF

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Publication number
WO1999035088A1
WO1999035088A1 PCT/EP1998/008498 EP9808498W WO9935088A1 WO 1999035088 A1 WO1999035088 A1 WO 1999035088A1 EP 9808498 W EP9808498 W EP 9808498W WO 9935088 A1 WO9935088 A1 WO 9935088A1
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WO
WIPO (PCT)
Prior art keywords
whose
compound
magnesium carbonate
pharmaceutical composition
aluminum magnesium
Prior art date
Application number
PCT/EP1998/008498
Other languages
English (en)
Inventor
Rafael Foguet
Santiago Gubert
Aurelio Sacristan
Josep M. Castello
José A. Ortiz
Original Assignee
Ferrer Internacional, S.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ferrer Internacional, S.A. filed Critical Ferrer Internacional, S.A.
Priority to IL13157398A priority Critical patent/IL131573A0/xx
Priority to EP98966416A priority patent/EP0968133A1/fr
Priority to PL98335464A priority patent/PL335464A1/xx
Priority to BR9807275-7A priority patent/BR9807275A/pt
Priority to JP53563199A priority patent/JP2001516328A/ja
Priority to AU22767/99A priority patent/AU742544B2/en
Priority to CA002282361A priority patent/CA2282361A1/fr
Publication of WO1999035088A1 publication Critical patent/WO1999035088A1/fr
Priority to NO994160A priority patent/NO994160L/no

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01F—COMPOUNDS OF THE METALS BERYLLIUM, MAGNESIUM, ALUMINIUM, CALCIUM, STRONTIUM, BARIUM, RADIUM, THORIUM, OR OF THE RARE-EARTH METALS
    • C01F7/00—Compounds of aluminium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/10—Carbonates; Bicarbonates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01F—COMPOUNDS OF THE METALS BERYLLIUM, MAGNESIUM, ALUMINIUM, CALCIUM, STRONTIUM, BARIUM, RADIUM, THORIUM, OR OF THE RARE-EARTH METALS
    • C01F7/00—Compounds of aluminium
    • C01F7/78—Compounds containing aluminium and two or more other elements, with the exception of oxygen and hydrogen
    • C01F7/784—Layered double hydroxide, e.g. comprising nitrate, sulfate or carbonate ions as intercalating anions
    • C01F7/785—Hydrotalcite
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2002/00—Crystal-structural characteristics
    • C01P2002/70—Crystal-structural characteristics defined by measured X-ray, neutron or electron diffraction data
    • C01P2002/72—Crystal-structural characteristics defined by measured X-ray, neutron or electron diffraction data by d-values or two theta-values, e.g. as X-ray diagram
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2002/00—Crystal-structural characteristics
    • C01P2002/70—Crystal-structural characteristics defined by measured X-ray, neutron or electron diffraction data
    • C01P2002/77—Crystal-structural characteristics defined by measured X-ray, neutron or electron diffraction data by unit-cell parameters, atom positions or structure diagrams
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2002/00—Crystal-structural characteristics
    • C01P2002/80—Crystal-structural characteristics defined by measured data other than those specified in group C01P2002/70
    • C01P2002/82—Crystal-structural characteristics defined by measured data other than those specified in group C01P2002/70 by IR- or Raman-data
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2002/00—Crystal-structural characteristics
    • C01P2002/80—Crystal-structural characteristics defined by measured data other than those specified in group C01P2002/70
    • C01P2002/88—Crystal-structural characteristics defined by measured data other than those specified in group C01P2002/70 by thermal analysis data, e.g. TGA, DTA, DSC
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/50—Agglomerated particles

Definitions

  • the compound of this invention is prepared by reacting aluminum hydroxide with magnesium hydroxide and sodium acid carbonate in an aqueous medium at the boiling temperature of the mixture.
  • the stoichiometric ratio of aluminum hydroxide to magnesium hydroxide should be 1:2.
  • the sodium acid carbonate is used in a molar excess, in such a way that the medium pH ranges between 9 and 11.
  • the crystalline cell volume is 183 A 3 and the X-ray diffraction spectrum shows the following d(A) values: 7.597; 3.798; 2.6202; 2.5698; 2.5322; 2.2830; 1.93545; 1.72447; 1.62930; 1.52289; 1.49318; 1.46002; 1.41351; 1.38528 and 1.31011 (Table 1).
  • H. K. L Sites of the reticular parameters of the compound (elemental cell) that allow to assign a triplet of indices or integers (H. K. L) to each line of diffraction.
  • 2- ⁇ Angular variable that shows the angular position where the line of diffraction (H. K. L) appears on the diagram. If the elemental cell of the compound and the triplet (H. K. L) are known, the theoretical position, which should coincide with the observed one, can be calculated (obs.: observed; cal . : calculated) .
  • Intensity It provides the height of the diffraction line, which is characteristic of the atomic positions in the crystalline cell, in contrast to the angular position, which is characteristic of the size of the crystalline cell.
  • aluminum magnesium carbonates are already known to be used as antacids in therapeutics.
  • aluminum magnesium carbonates those prepared in accordance with US Patents Nos . 3,539,306 and 3,650,704 (hydrotalcyte [TalcidTM] of the formula Al 2 Mg 6 (OH) 16 CO 3 .4H 2 0) , US Patents Nos. 4,447,417 and 4,560,545 (almagate [AlmaxTM and AlmaxTM Forte] of the formula Al 2 g s (OH) (C0 3 ) 2 .4H 2 0, and US Patent No. 4,539,195 (compound of the formula Al 2 Mg 6 (OH) 12 (C0 3 ) 3 .xH 2 0) can be used.
  • the compound of the present invention (I) is different from the compounds disclosed in the aforesaid patents and does not turn to be obvious despite the similarity between their chemical formulas.
  • the compound (I) has a unique crystalline structure as evidenced by its X-ray diffraction spectrum (Table 1) .
  • the DSC thermogram shows the presence of a properly structured unique compound ( Figure 2) .
  • the compound of this invention has antacid properties and also exhibits an advantageous superior gastroprotective activity over known compounds.
  • Irwin test The technique described by R.A. Turner ⁇ Screening Methods in Pharmacology, 1965, p. 27-34. Academic Press, New York and London) was employed.
  • the compound of Example 1 and almagate were orally administered to Swiss mice of either sex at doses of 0.3 , 1 and 3 g/kg in a volume of 30 mL/kg. None of the three doses tested induced changes in the parameters assessed (awareness and mood, reflexes, motor activity, CNS excitation, muscle tone, optical signs, secretory-excretory signs, general signs, acute mortality and delayed mortality) in either group, and the absence of changes in the defecation and mortality should be emphasized. Therefore, Irwin test revealed the safety of the compound of Example 1 and almagate.
  • Antacid activi ty Measurement of the antacid activity was performed in female Wistar rats, weighing 140 - 160 g. The animals were housed in metabolism cages and fasted from 24 h before the experiment to 1 h before the start of experiment but with free access to water. The animals were anesthetized with a mixture of Ketolar (91 mg/kg) and Tiazine (3.6 mg/kg) and then laparotomized; the pylorus was carefully ligated and the abdominal cavity was closed using a sterile suture (H. Shay et al . "Gastroenterology", 1954, 5_, 43-61). Three hours after the pyloric ligature, test drugs were given orally to the conscious animals.
  • One group of 10 animals received the compound of Example 1 in 0.25% Bacto-agar suspension at a dose of 125 mg/kg and another group of 10 animals at a dose of 62.5 mg/kg; a control group of 10 animals dosed with 10 mL/kg of 0.25% Bacto-agar was used. Similarly, the experiment was repeated with almagate at the same doses and using the same number of animals; a new control group of 10 animals was given the same dose of Bacto-agar as in the experiment with the compound of Example 1. Sixty minutes after the administration, the animals were sacrificed, the gastric contents was collected and volume was determined.
  • Gastroprotective activi ty To measure the gastroprotective activity the experimental method of ethanol -induced gastric necrosis described by A. Robert et al . ( Gastroenterology, 1979, 21(3), 433-443) was employed. The experiment was carried out in female Sprague-Dawley rats weighing 180-200 g which were fasted since 24 h before the start of experiment. The compound of this invention was compared to almagate in the same manner as in the preceding test. The compound of Example 1 was administered in a 0.25% Bacto-agar suspension. Both test products were administered orally at doses of 100 and 50 mg/kg. Simultaneously, a control group received 0.25% Bacto-agar. After 30 minutes, the animals were given absolute ethanol at a dose of 1 mL/rat. Sixty minutes after ethanol administration, the animals were sacrificed and the length of lesions in the gastric mucosa measured. The results obtained are tabulated in Table 3.
  • the compound of this invention is characterized by inhibiting the stomach acid secretion, minimizing the aggressive factors on the gastric mucosa and, in addition, exhibiting a surprising gastroprotective action.
  • the gastroprotection afforded by the compound of this invention has a higher potency and longer duration than almagate, which advantageously results in a much more effective improvement of the defense mechanisms of gastric mucosa.
  • the therapeutic application of the compound of this invention is as an antacid and gastroprotector, and can be administered to treat hyperchlorhydria, gastritis, gastroduodenitis, dyspepsia, esophagitis, diverticulitis, hyatal hernia, gastric and duodenal ulcers, gastric post-operated patients, vagotomized patients and, in general, to alleviate all those disturbances or episodes causing increased acidity in the stomach.
  • the compound of this invention mixed with suitable carriers can be administered orally at daily doses ranging from 250 mg to 10 g, preferably between 1 and 6 g, in the form of suspensions, granules, tablets, capsules, powders, coated tablets and the like.
  • Example 1 Aluminum magnesium carbonate hydroxide trihyrate Al 2 Mg ask(OH) 12 C0.3H 2 0) (I)
  • This suspension may be inserted in 100 -mL containers or in unidose 15 -mL sachets containing 1.5 g of active ingredient.
  • Example 3 Preparation of a dispersible granulate of aluminum magnesium carbonate hydroxide trihydrate
  • Formulation per 5 g of granulate aluminum magnesium carbonate hydroxide trihydrate 1.50 g dimethylpolysiloxane 0.20 g sorbitol powder 1.00 g sodium saccharin 0.01 g polyvinylpyrrolidone K-25 0.03 g butylhydroxytoluene 0.0005 g lemon flavour 0.0050 g skim powdered milk q.s 5.0000 g
  • This granulate is placed in unidose sachets for its dispersion in water.
  • These tablets may be inserted in aluminium tubes or blister and are dissolved in the mouth or chewed.

Abstract

L'invention concerne un nouveau carbonate basique de magnésium et d'aluminium, de formule Al2Mg4(OH)12CO3.3H2O (I) et à cristallisation rhomboédrique, dont les paramètres réticulaires sont a = b = 3,046 Å; c = 22,79 Å; α = β = 90°; η = 120° et dont le volume cellulaire est égal à 183 A3; dont le spectre de diffraction des rayons X présente les valeurs d(Å) suivantes: 7,597; 3,798; 2,6202; 2,5698; 2,5322; 2,2830; 1,93545; 1,72447; 1,62930; 1,52289; 1,49318; 1,46002; 1,41351; 1,38528 et 1,31011; dont le spectre infrarouge présente des bandes caractéristiques à 1361 et 449 cm-1 (figure 1) et dont l'analyse enthalpique différentielle (DSC) est illustrée par la figure 2. Ce composé est utile en thérapeutique en tant qu'antiacide et gastroprotecteur.
PCT/EP1998/008498 1997-12-30 1998-12-29 Carbonate basique de magnesium et d'aluminium, son procede de fabrication et son utilisation comme composition pharmaceutique destinee au traitement de l'acidite gastrique WO1999035088A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
IL13157398A IL131573A0 (en) 1997-12-30 1998-12-29 Basic aluminum magnesium caronate method for the preparation thereof and its use as a pharmaceutical composition for treating stomach acidity
EP98966416A EP0968133A1 (fr) 1997-12-30 1998-12-29 Carbonate basique de magnesium et d'aluminium, son procede de fabrication et son utilisation comme composition pharmaceutique destinee au traitement de l'acidite gastrique
PL98335464A PL335464A1 (en) 1997-12-30 1998-12-29 Basic aluminium-magnesium carbonate
BR9807275-7A BR9807275A (pt) 1997-12-30 1998-12-29 Carbonato básico de alumìnio e magnésio
JP53563199A JP2001516328A (ja) 1997-12-30 1998-12-29 塩基性炭酸マグネシウムアルミニウム、その製造方法および胃酸性度を治療するための製薬組成物としてのその使用
AU22767/99A AU742544B2 (en) 1997-12-30 1998-12-29 Basic aluminum magnesium carbonate, method for the preparation thereof and its use as a pharmaceutical composition for treating stomach acidity
CA002282361A CA2282361A1 (fr) 1997-12-30 1998-12-29 Carbonate basique de magnesium et d'aluminium, son procede de fabrication et son utilisation comme composition pharmaceutique destinee au traitement de l'acidite gastrique
NO994160A NO994160L (no) 1997-12-30 1999-08-27 Basisk aluminium-magnesiumkarbonat, fremgangsmaate for fremstilling derav og dets anvendelse som et farmasöytisk preparat for behandling av magesurhet

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES9702717 1997-12-30
ES009702717A ES2133136B1 (es) 1997-12-30 1997-12-30 Nuevo carbonato basico de aluminio y magnesio.

Publications (1)

Publication Number Publication Date
WO1999035088A1 true WO1999035088A1 (fr) 1999-07-15

Family

ID=8301660

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/008498 WO1999035088A1 (fr) 1997-12-30 1998-12-29 Carbonate basique de magnesium et d'aluminium, son procede de fabrication et son utilisation comme composition pharmaceutique destinee au traitement de l'acidite gastrique

Country Status (15)

Country Link
EP (1) EP0968133A1 (fr)
JP (1) JP2001516328A (fr)
KR (1) KR20000075839A (fr)
AR (1) AR007232A1 (fr)
AU (1) AU742544B2 (fr)
BR (1) BR9807275A (fr)
CA (1) CA2282361A1 (fr)
ES (1) ES2133136B1 (fr)
IL (1) IL131573A0 (fr)
NO (1) NO994160L (fr)
PA (1) PA8464401A1 (fr)
PL (1) PL335464A1 (fr)
RU (1) RU2168464C1 (fr)
WO (1) WO1999035088A1 (fr)
ZA (1) ZA9811216B (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108159072A (zh) * 2017-12-04 2018-06-15 上海裕英生物医药科技有限公司 铝镁加的制备工艺

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4338470B2 (ja) * 2003-08-12 2009-10-07 日鉄鉱業株式会社 ハイドロタルサイト粒子及びその製造方法
RU2540635C2 (ru) * 2012-11-22 2015-02-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Национальный минерально-сырьевой университет "Горный" Способ получения гидрокарбоалюминатов щелочноземельных металлов из природного магнийсодержащего сырья
RU2678007C1 (ru) * 2017-12-05 2019-01-22 Федеральное государственное бюджетное учреждение науки Федеральный исследовательский центр "Кольский научный центр Российской академии наук" (ФИЦ КНЦ РАН) Способ получения слоистого гидроксида магния и алюминия

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0117289A2 (fr) * 1983-02-26 1984-09-05 Giulini Chemie GmbH Hydroxycarbonate de magnésium et d'aluminium basique
US4904457A (en) * 1974-03-30 1990-02-27 Aluminum Company Of America Synthetic hydrotalcite
WO1996005140A1 (fr) * 1994-08-15 1996-02-22 Aluminum Company Of America Synthese d'hydrotalcite et de composes apparentes, a partir de deux poudres

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3539306A (en) * 1966-07-25 1970-11-10 Kyowa Chem Ind Co Ltd Process for the preparation of hydrotalcite
GB1598375A (en) * 1978-02-17 1981-09-16 Anphar Sa Aluminium magnesium carbonate

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4904457A (en) * 1974-03-30 1990-02-27 Aluminum Company Of America Synthetic hydrotalcite
EP0117289A2 (fr) * 1983-02-26 1984-09-05 Giulini Chemie GmbH Hydroxycarbonate de magnésium et d'aluminium basique
WO1996005140A1 (fr) * 1994-08-15 1996-02-22 Aluminum Company Of America Synthese d'hydrotalcite et de composes apparentes, a partir de deux poudres

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
I. PAUSCH ET AL.: "Synthesis of disordered and Al-rich hydrotalcite-like compounds.", CLAYS AND CLAY MINERALS, vol. 34, no. 5, 1986, pages 507 - 510, XP002101577 *
R. ALLMANN: "Doppelschichtstrukturen mit brucitähnlichen Schichtionen.", CHIMIA, vol. 24, March 1970 (1970-03-01), pages 99 - 108, XP002101576 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108159072A (zh) * 2017-12-04 2018-06-15 上海裕英生物医药科技有限公司 铝镁加的制备工艺

Also Published As

Publication number Publication date
BR9807275A (pt) 2000-05-02
ES2133136A1 (es) 1999-08-16
AU2276799A (en) 1999-07-26
AR007232A1 (es) 1999-10-27
KR20000075839A (ko) 2000-12-26
IL131573A0 (en) 2001-01-28
EP0968133A1 (fr) 2000-01-05
AU742544B2 (en) 2002-01-03
CA2282361A1 (fr) 1999-07-15
RU2168464C1 (ru) 2001-06-10
ES2133136B1 (es) 2000-04-01
PL335464A1 (en) 2000-04-25
ZA9811216B (en) 1999-07-14
PA8464401A1 (es) 2000-09-29
NO994160D0 (no) 1999-08-27
NO994160L (no) 1999-08-27
JP2001516328A (ja) 2001-09-25

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