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GB1564135A - Readily-assimilatable highly-soluble calcium and/or magnesium organic salts - Google Patents

Readily-assimilatable highly-soluble calcium and/or magnesium organic salts Download PDF

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Publication number
GB1564135A
GB1564135A GB31669/76A GB3166976A GB1564135A GB 1564135 A GB1564135 A GB 1564135A GB 31669/76 A GB31669/76 A GB 31669/76A GB 3166976 A GB3166976 A GB 3166976A GB 1564135 A GB1564135 A GB 1564135A
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United Kingdom
Prior art keywords
magnesium
calcium
water
salts
solution
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Expired
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GB31669/76A
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BUCURESTI MEDICAMENTE
Zentiva SA
Original Assignee
BUCURESTI MEDICAMENTE
Intreprinderea de Medicamente Bucuresti
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Publication of GB1564135A publication Critical patent/GB1564135A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/145—Amines having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A61K47/585—Ion exchange resins, e.g. polystyrene sulfonic acid resin

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Rapidly assimilable and readily soluble calcium and magnesium double salts of organic acids, such as lactic acid, gluconic acid, glutamic acid, and pantothenic acid, are prepared by dissolving respectively calcium and magnesium salts of these acids separately in a multiple amount of water and mixing the resulting solutions with one another in such a ratio that the molar ratio of the two salts in the mixture is from 0.5-1 : 1-0.5. This solution mixture is then heated to temperatures between 20 and 60 DEG C for 30 minutes to 2 hours and the resulting double salt is separated off by atomising or precipitation with organic solvents.

Description

(54) READILY-ASSIMILATABLE, HIGHLY-SOLUBLE CALCIUM AND/OR MAGNESIUM ORGANIC SALTS (71) We, INTREPRINDEREA DE MEDICAMENTE BUCURESTI, a Rumanian State Enterprise of Blvd. Ion Sulea No. 246, Bucharest, Rumania, do hereby declare the invention, for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: This invention relates to a readily-assimilatable, highly soluble composition of calcium and/or magnesium organic salts intended for internal medicinal use.
Calcium is an indispensable element for the human body as it ensures good functioning of the body and maintains the functional integrity of the central and peripheral parts of the nervous system. It is also necessary for a normal cardiac function and it is one of the factors involved in blood clotting. Calcium salts form the structural framework of the bone system.
Magnesium has also a great physiological importance and is of particular pharmacologic interest. It is necessary for ensuring the functional integrity of the neuro-muscular system.
Magnesium acts upon the activity of a great number of enzymatic systems, such as adenosinetriphosphatase, cholinesterase, cholinocytilase.
Most calcium or magnesium organic salts are slightly soluble in water. In order to facilitate their assimilation at the level of the digestive tract it is necessary for them to be in the form of readily soluble salts.
At present for therapeutic purposes there are used calcium organic salts of the calcium gluconate type which are easily assimilatable because of their high degree of solubility. As regards magnesium, well known preparations such as magnesium citrate or sulphate, are usually used in view of their action on the gastro-intestinal tract. Magnesium oxide or carbonate are also used as specific antacids.
Compositions made of double calcium organic salts such as calcium gluconate with calcium lactobionate or calcium gluconate with calcium glucoheptonate, or calcium gluconate with calcium levulinate, are also well-known.
As a method of preparing the double calcium salts, it is usual to mix the solution obtained on heating from the two calcium salts and then to precipitate the double salt in the solution with ethyl alcohol. The composition calcium gluconate and calcium glutamate is prepared by stirring calcium gluconate solution with glutamic acid and calcium carbonate in aqueous solutions, until effervescence stops, heating the mixture obtained for an hour in a water-bath, then filtrating it and adding vitamin C and an antioxidant (such as thioglycolic acid) for rendering it stable.
Other methods used for rendering soluble the calcium organic salts for pharmaceutical preparations rely on amino acids, especially synthetic ones or amino acids obtained from protein hydrolysis, which act as solubilizers.
According to the present invention there is provided a composition of soluble organic calcium and/or magnesium salts characterised by the fact that it is made of double salts of calcium and magnesium or of magnesium only of different organic acids, having the general formula: HOOC - (CH2)n - Rm - (CHOH)x where: n=0-2 Rm = -CONH- or -CH(NHz)- or m = 0 x=0-4 R' = an alkyl group with 1 to 4 carbon atoms, -COOH, - CH2OH, -C(CH3)2.CH2OH where the molar ratio between the two salts ranges from 0.5 to 1:1 to 0.5.
The invention also provides a method of preparing the composition described in the preceding paragraph, said method being characterised by the fact that it comprises: separate dissolution of the component salts in water in the ratio 2 to 7 parts by weight water to one part by weight salt, mixing of the obtained solutions and their heating at a temperature of 20 to 60"C for 30 minutes to 2 hours, and then separation of the active product from the solution by evaporation or precipitating it with organic solvents.
Examples of the method will now be described. In the Examples, all references to parts and to percentages are by weight.
Example I Dissolve 215 g calcium gluconate in 430 g water with heating and mix, at 200C, with a solution obtained by dissolving 202 g, magnesium lactate in 404 g water. Keep the solution thus obtained at 20"C for 30 minutes and then purify it on charcoal or another absorbent material (active earths, Celite (Registered Trade Mark)) and filter. Separate the active composition calcium gluconate/magnesium lactate from the filtrate either by direct atomization (i.e. fast evaporation), at a temperature of the solution ranging from 20 to 60"C, or by precipitating it with organic solvents such as alcohols, acetone, ethers with cooling (temperature ranging from 0 to 50C). Filter the suspension obtained by precipitation and dry the precipitate.
The dry substance obtained either by fast evaporation or by precipitating, is packed in various dosage forms (injectable solution, effervescent tablets, capsules, tablets, sugarcoated tablets) according to known techniques. The product obtained is more soluble than the known double calcium salts. its solubility is one part product to 2-3 parts water. Calcium content per cent ranges from 4.5 to 6.9 and magnesium content from 2 to 5.4.
Example 2 Dissolve 430 g calcium gluconate in 3010 g water and mix at 600C with a solution obtained by dissolving 101 g magnesium lactate in 707 g water; Keep the solution thus obtained for 2 hours at 60"C. Continue as in Example 1 to obtain the dry product made of calcium gluconate/magnesium lactate.
Example 3 Dissolve 207 g magnesium gluconate in 414 g water and mix at 60"C with a solution obtained from 218 calcium lactate in 872 g water. Keep the solution for 30 minutes at 600C.
Continue as in Example 1 to obtain the final dry product - magnesium gluconate/calcium lactate.
Example 4 Dissolve 207 g magnesium gluconate on heating in 1449 g water and mix at 350C with a solution obtained from 202 g magnesium lactate dissolved in 1414 g water. Keep the mixture for 2 hours at 35"C. Continue as in Example 1 to obtain the product magnesium gluconate/magnesium lactate.
Example 5 Dissolve 414 g magnesium gluconate in 824 g water on heating and mix with a solution obtained by dissolving 101 g magnesium lactate in 303 g water. Keep the mixture at 60"C for one hour. Continue as in Example 1 to obtain the dry product magnesium gluconatel magnesium lactate.
Example 6 Dissolve 187 g calcium glutamate, on heating, in 1309 g water and mix with a solution obtained from 202 g magnesium lactate dissolved in 1414 g water. Keep the mixture at 600C for 2 hours. Continue as in Example 1, to obtain the dry product calcium glutamatel magnesium lactate.
Example 7 Dissolve 476 g calcium pantothenate in 3332 g water, mix the solution obtained with a solution obtained from 202 g magnesium lactate dissolved in 1414 g water. Keep the mixture for 30 minutes at 35"C. Continue as in Example 1 to obtain the dry product calcium pantothenate/magnesium lactate.
Example 8 Dissolve 238 g calcium pantothenate in 714 g water on heating and mix the solution with a solution obtained from 207 g magnesium gluconate dissolved in 621 g water. Keep the mixture for 30 minutes at 40"C and continue as in Example 1 to obtain the dry product calcium pantothenate/magnesium gluconate.
Example 9 Dissolve 460 g magnesium panthothenate in 3220 g water. Mix the solution with a solution obtain from 430 g calcium gluconate dissolved in 3010 g water. Keep the mixture for 2 hours at 400C. Continue as in Example 1 to obtain the dry product magnesium pantothenate/calcium gluconate.
Example 10 Dissolve on heating 460 g magnesium pantothenate in 920 g water. Mix the solution with a solution obtained from 207 g magnesium gluconate dissolved in 414 g water. Keep the mixture for 30 minutes at 30"C and then continue as in Example 1 to obtain the dry product magnesium pantothenate/magnesium gluconate.
Example 11 Dissolve 109 g calcium lactate in 218 g water and mix the solution with a solution obtained on heating from 414 g magnesium gluconate dissolved in 828 g water. Keep the mixture for 2 hours at 60"C. Continue as in Example 1 to obtain the dry product calcium lactate/magnesium gluconate.
Example 12 Dissolve 218 g calcium lactate in 436 g water and the mix with a solution obtained on heating from 158 g magnesium glutamate dissolved in 316 g water. Keep the mixture at 30"C for 30 minutes. Continue as in Example 1 to obtain the dry product calcium lactate/ magnesium glutamate.
The advantages to be achieved with the product of the above Examples are as follows: The compositions of calcium and magnesium salts or only of magnesium salts are very readily assimilatable as they gave a high degree of solubility.
The content of calcium ranges from 4.5% to 6.9% and of magnesium from 2% to 5.4% in the mixtures of calcium and magnesium salts. In the mixtures made only of organic magnesium salts, the content of magnesium ranges from 5.4% to 10%.
WHAT WE CLAIM IS: 1. Composition of soluble organic calcium and/or magnesium salts, characterised by the fact that it is made of double salts of calcium and magnesium or of magnesium only of different organic acids, having the general formula: HOOC - (CH2)n - Rm - (CHOH)x where: n=0-2 Rm = -CONH- or -CH(NH2)- or m = 0 x=0-4 R' = an alkyl group with 1 to 4 carbon atoms, -COOH, -CH2OH, -C(CH3)2oCH2OH where the molar ratio between the two salts ranges from 0.5 to 1:1 to 0.5.
2. Method of preparing the composition of claim 1, characterised by the fact that it comprises: separate dissolution of the component salts in water in the ratio 2 to 7 parts by weight water to one part by weight salt, mixing of the obtained solutions and their heating at a temperature of 20 to 60"C for 30 minutes to 2 hours, and then separation of the active product from the solution by evaporation or precipitating it with organic solvents.
3. A composition or method substantially as hereinbefore described with reference to any of the Examples.
4. A composition according to claim 1 which in the case of calcium/magnesium double
**WARNING** end of DESC field may overlap start of CLMS **.

Claims (5)

**WARNING** start of CLMS field may overlap end of DESC **. solution obtained from 202 g magnesium lactate dissolved in 1414 g water. Keep the mixture for 30 minutes at 35"C. Continue as in Example 1 to obtain the dry product calcium pantothenate/magnesium lactate. Example 8 Dissolve 238 g calcium pantothenate in 714 g water on heating and mix the solution with a solution obtained from 207 g magnesium gluconate dissolved in 621 g water. Keep the mixture for 30 minutes at 40"C and continue as in Example 1 to obtain the dry product calcium pantothenate/magnesium gluconate. Example 9 Dissolve 460 g magnesium panthothenate in 3220 g water. Mix the solution with a solution obtain from 430 g calcium gluconate dissolved in 3010 g water. Keep the mixture for 2 hours at 400C. Continue as in Example 1 to obtain the dry product magnesium pantothenate/calcium gluconate. Example 10 Dissolve on heating 460 g magnesium pantothenate in 920 g water. Mix the solution with a solution obtained from 207 g magnesium gluconate dissolved in 414 g water. Keep the mixture for 30 minutes at 30"C and then continue as in Example 1 to obtain the dry product magnesium pantothenate/magnesium gluconate. Example 11 Dissolve 109 g calcium lactate in 218 g water and mix the solution with a solution obtained on heating from 414 g magnesium gluconate dissolved in 828 g water. Keep the mixture for 2 hours at 60"C. Continue as in Example 1 to obtain the dry product calcium lactate/magnesium gluconate. Example 12 Dissolve 218 g calcium lactate in 436 g water and the mix with a solution obtained on heating from 158 g magnesium glutamate dissolved in 316 g water. Keep the mixture at 30"C for 30 minutes. Continue as in Example 1 to obtain the dry product calcium lactate/ magnesium glutamate. The advantages to be achieved with the product of the above Examples are as follows: The compositions of calcium and magnesium salts or only of magnesium salts are very readily assimilatable as they gave a high degree of solubility. The content of calcium ranges from 4.5% to 6.9% and of magnesium from 2% to 5.4% in the mixtures of calcium and magnesium salts. In the mixtures made only of organic magnesium salts, the content of magnesium ranges from 5.4% to 10%. WHAT WE CLAIM IS:
1. Composition of soluble organic calcium and/or magnesium salts, characterised by the fact that it is made of double salts of calcium and magnesium or of magnesium only of different organic acids, having the general formula: HOOC - (CH2)n - Rm - (CHOH)x where: n=0-2 Rm = -CONH- or -CH(NH2)- or m = 0 x=0-4 R' = an alkyl group with 1 to 4 carbon atoms, -COOH, -CH2OH, -C(CH3)2oCH2OH where the molar ratio between the two salts ranges from 0.5 to 1:1 to 0.5.
2. Method of preparing the composition of claim 1, characterised by the fact that it comprises: separate dissolution of the component salts in water in the ratio 2 to 7 parts by weight water to one part by weight salt, mixing of the obtained solutions and their heating at a temperature of 20 to 60"C for 30 minutes to 2 hours, and then separation of the active product from the solution by evaporation or precipitating it with organic solvents.
3. A composition or method substantially as hereinbefore described with reference to any of the Examples.
4. A composition according to claim 1 which in the case of calcium/magnesium double
salts has 4.5 to 6.9% by weight calcium and 2 to
5.4% by weight magnesium and in the case of double magnesium salts has 5.4 to 10% by weight magnesium.
GB31669/76A 1975-08-05 1976-07-29 Readily-assimilatable highly-soluble calcium and/or magnesium organic salts Expired GB1564135A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
RO7583091A RO68298A2 (en) 1975-08-05 1975-08-05 COMPOSITION BASED ON ORGANIC CALCIUM AND MAGNESIUM SALTS EASILY ASSIMILABLE WITH INCREASED SOLUBILITY AND THE PREPARATION PROCESS

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GB1564135A true GB1564135A (en) 1980-04-02

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GB31669/76A Expired GB1564135A (en) 1975-08-05 1976-07-29 Readily-assimilatable highly-soluble calcium and/or magnesium organic salts

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JP (1) JPS54122216A (en)
CH (1) CH625503A5 (en)
DE (1) DE2635293A1 (en)
FR (1) FR2320089A1 (en)
GB (1) GB1564135A (en)
IN (1) IN144366B (en)
RO (1) RO68298A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101209962B (en) * 2006-12-28 2011-08-24 浙江山下湖珍珠集团股份有限公司 Method for preparing calcium magnesium gluconate

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LU84891A1 (en) * 1983-06-30 1985-03-29 Continental Pharma 2-AMINOACETIC ACID DERIVATIVES, THEIR PREPARATION AND USE AS WELL AS PHARMACEUTICAL COMPOSITIONS CONTAINING THESE DERIVATIVES
US5089276A (en) * 1989-04-19 1992-02-18 Takeda Chemical Industries, Ltd. Calcium pantothenate composite
GB8926486D0 (en) * 1989-11-23 1990-01-10 Ciba Geigy Pesticide composition

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2454164A1 (en) * 1974-11-15 1976-05-26 Tad Pharm Werk Injections against magnesium tetany in ruminants - contg. a basic magnesium salt of acetylglutamic acid

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101209962B (en) * 2006-12-28 2011-08-24 浙江山下湖珍珠集团股份有限公司 Method for preparing calcium magnesium gluconate

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Publication number Publication date
DE2635293A1 (en) 1977-05-12
FR2320089A1 (en) 1977-03-04
JPS54122216A (en) 1979-09-21
FR2320089B1 (en) 1978-11-17
CH625503A5 (en) 1981-09-30
RO68298A2 (en) 1980-04-15
JPS5761728B2 (en) 1982-12-25
IN144366B (en) 1978-04-29

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