BASIC METAL COMPLEXES OF ACIDIC OLIGO- AND POLYSACCHARIDES AND FRUIT AND VEGETABLE PRODUCTS AND PHARMACEUTICAL COMPOSITIONS COMPRISING SUCH COMPLEXES

Abstract: The invention relates to a metal complex of formula (I), wherein M<z+> is an alkaline earth metal ion and/or a transition metal ion with 3d orbital, z is the charge number of cation M<z+>, M<+> is an alkali metal ion, Ps<-> represents a monomeric unit of an acidic oligo- or polysaccharide chain comprising one carboxylate group, Ps represents one neutral carbohydrate unit of an acidic oligo- or polysaccharide chain, a1 is the stoichiometric coefficinet of the hydroxy ligands, a2 is the stoichiometric coefficient of the hydrocarbonate ligands, a3 is the stoichiometric coefficient of the carbonate ligands, x and y are the stoichiometric coefficients of the individual structural units of the saccharide chain, and n is the polymerization degree of the polysaccharide chain built up from the above structural units, with the proviso that any one of a1, a2 and a3 may be equal to zero but the sum of a1, a2 and a3 is always greater than zero, and the maximum value of the sum of a1, a2 and 2a3 is equal to z-1. The invention also relates to a pharmaceutical composition, to a fruit or vegetable juice and to a fruit-containing gel comprising a compound of formula (I). Furthermore, the invention relates to a method for preparing a compound of formula (I).

Description: BASIC IvΞTAL COMPLSXSS OF ACIDIC OLIGO- AM ) P0LYSACCHARID3S AND FRUIT AND V3GSTAEL3 PRODUCTS AND PHARMACEUTICAL COMPOSI TIONS COMPRISING SUCH C0MPLE.X.3S The invention relates to basic metal complexes of acidic oligo- and polysaccharides. The invention also relat to pharmaceutical compositions, fruit-containing gels and fruit and vegetable juices comprising such metal complexeso Furthermore, the invention relates to a method for the pre¬ paration of metal complexes containing basic groups, in particular, hydroxy, hydro carbonate and/or carbonate ligand from acidic oligo- and polysaccharides o It is well known that alkali metal ions (such as Na + , K + , Li + ) , alkaline earth metsl ions (such as Mg 2+ , Ca 2+ Sr ) and transition metal ions with 3d orbitals (such as Cr 3+ , Mn 2+ , Fe 2+/3+ , Co 2+ , Zn 2+ , Ni + , Cu 2+ , VO 2+ , etc.) are indispensible factors for the normal functions of living organismso These metal ions are termed in the following as "essential metal ions". Essential metal ions are components or activators of numerous enzyme systems, they are in close correlation with the level of certain vitamins in the livin organism, and have an essential influence on the functionin of hormone systems,, Any deficiency in essential metal ion level may involve a decrease in the synthesis of important proteins, enzymes, hormones and other biologically active substances which regulate the normal functions of the whole living organism. It is also well known that the essential metal io content of foodstuf s of plant and animal origin shows a steadily decreasing tendency,, The reason for this fact is that, owing to increasingly intense plant cultivation, the macro- and microelement resources of soil available for plants teadily decrease, and the processing, purifying and refining techniques applied in foodstuff industry further decrease the low initial essential metal ion content of the raw materials,, The daily average trace element intake per capita calculated frαm the average trace element content of food¬ stuffs available in Hungary and from the average foodstuff consumption per capita _Szotyor -Lindner, K„ and Gergely, A. Nahrung 28, 7S9-796 (190 -27 " compared to the recommended amounts jSchelenz, R.: "Dietary recommendation for trace element intake" in Trace Element - Anal. Chem. in Medicine and Biology 4, 79-105 (βd„: Bratter, P β and Schramel, D β ; issued by W. de Gruntnar and Co β , Berlin - New York /1987/] is given in Table I β Table I Average intake from Recommended values ( g/day) ϋlement foodstuff in 1980 ( mg/day) Cu 0,95 Zn 10.57 e 9o75 Mn 1,21 Co Ool Ni 0 Cr 0,11 Mo 0 Mg 200 The data of Table I indicate that the trace element intake available from foodstuff is much less than necessary thus trace elements (essential metal ions) should be supple mented from other resources 0 It is well known that trace element intake can be increased by incorporating essential metal ions into food¬ stuffs or by administering essεntiεl metal ion-containing pharmaceutical compositions. According to the earliest method essential metal ions were administered orally in the form o inorganic salts or simple organic salts either as a food- stuff supplement or as a phεrmsceu icsl composition 0 Am. Dietetic Assoc. 2, 27 (1971)_7° However, in the living organ¬ ism, these " inorganic salts or simple organic salts and metal complexes of low stability constant (such εs lactates, acet¬ ates, etc.) form sparingly soluble compounds with the other foodstuff components or digestion products thereof, and in this form they are excreted from the organism without any notable biological utilization. As a further disadvantage, these simple metal salts have generally an unpleasant taste which strongly restricts the amount of metal salts introduc- ible into foodstuffs. Moreover, the metal salts catalyze the decomposition of the majority of oxidisable vitamins present in foodstuffs. Ferrous sulfate, whic is frequently utilized as metal salt additive optionally in combination with vitami C, produces free -OH and -E0 2 radicals under aerobic condi- tions, which may lead to undesire side effects particularly upon prolonged administration. It has also been attempted to apply essential metal ions in the form of their amino acid complexes with medium stability constants as foodstuff supplements. However, such metal complexes of amino acids do not build into the glyco- protein or protein system of the carrier foodstuff in un¬ changed form, but they dissociate first and are then meta¬ bolized separately. Under such conditions, like the simple metal salts, they convert into sparingly soluble compounds and are excreted from the organism without any notable bio¬ logical effect. On the other hand, essential metal ion complexes with high stability constants (such as citrates and iDTA complexe are useless as essential metal ion resources, since, owing t the high stability of the complexes, they are unable to pass their metal ion content to the living organism. Subsequent investigations revealed that the problem connected with the biological metabolism and utilization of essential metal ions can be mostly overcome when they are introduced into the living organism in the form of appropria selected biopolymer - etel chelεtes. The use of humic acid, alginic acid, pectin or degraded casein as biopolymer was suggested by Hungarian Patent No, 158,252, Japanese Patent No. 15,090 and Belgian Patents Nos. 619 > 267 and 652,508. It is a disadvantage, how¬ ever, that the starting bio polymers are not chemically v/ell defined substances but materials highly varying in compositi thus in metal binding capacity, too, consequently they do no enable one to prepare metal complexes in a reproducible mann with stable composition and steady quality. Considering the increasingly severe quality prescriptions set up in connec¬ tion with foodstuffs, these biopolymer - metal complexes can not be applied as foodstuff supplements. According to Yakugaku Zasshi 20, 120-126 and 1480- -1487 (1970) chondroitinε sulfatε is applied as biopolymer. Although this compound is a well defined substance from both chemical and biological aspects, its natural resources are rather limited, and the separation and purification of the biopolymer is a very sophisticated and laboursome operation. Thus, owing to the high production expenses, these biopolyme - metal complexes have only a rather restricted use in the mass production of foodstuffs. The preparation and biological effects of essential metal ion complexes of oligo- and polygalacturonic acids are disclosed in J. Polymer Sci. 10, 257-293 (1972) and in Hung¬ arian Patent No, 172,831, These metal complexes have the structural characteristic that the essential metal ions are connected to the -COO " and sugar -OH groups of the polygalact uronatβ skeleton, thus the bivalent essential metal ions lin two, and the trivalent essential metal ions link three poly- galacturonate chains. Although polygalacturonic acid utilize as biopolymer is a chemically well defined and easily avail- able substance, thus it can be regarded as an ideal "support" for metal ions, it is a disadvantage that the essential metal ions metabolize rather slowly from these metal complexes. The greater the molecular weight of polygalacturonic acid, the slower the metabolization rate of the metal ion. This is most clearly demonstrated by the fact that metal complexe formed with polygalacturonic acids with a polymerization degree higher than 150 are no more applied to introduce esse tial metal ions into the organism but to remove toxic metal ions (such as lead or radioactive strontium) from the organ- ism Chem. Abstr, 35, 88175f (1975)7• Metal complexes formed with polygalacturonic acids with a polymerization degree of 10 to 145 are still able to pass their metal ion content to the organism. Considering, however, that two or three poly¬ galacturonic acid chains should be split in order to liberate the metal ion, this proceeds under biological conditions rather slowly and the decomposition is sometimes incomplete. As a further disadvantage, these polygalacturonate - metal complexes are difficult to incorporate into the raw material of food industry; the homogenization of small amounts of complex supplements is particularly difficult. The above poly galacturonate - metal complexes are sparingly soluble i water, thus they can be added to juices and beverages only in small amounts, and they segregate from the liquid after a more or less prolonged storage. Now it has been found that when metal complexes are prepared from acidic polysaccharides in which the complexed metal ions or any desired proportion of them are attached with a least one of their valences to the -COO " groups of the acidic polysaccharide skeleton and at the same time thes metal ions are attached with at least one further valence to a hydroxy, carbonate or hydro carbonate ligand, "basic" metal complexes are formed from which the metal ions liberate with an increased rate under biological conditions and the complexes pass their complete metal ion content to the livin organism in biologically utilizable form. This latter re¬ cognition is very surprising, since it was to be expected that in the presence of the basic ligands (hydroxy, carbonat and hydrocarbona te ligands) the metal ions would form less soluble compounds than those formed from neutral complexes which would involve a considerable loss in their biological utility. Our practical experiences are, however, in a full contrast with these expectations. It has also been found that these basic metal complexes, when admixed with fruit or vegetable juices or fruit-containing gels, e;:ert favourable stabilizing, consist ency-improving and gelling effects without any decrease in their biological value. Thus these basic me al complexes can be applied to advantage as supplements for fruit or vegetabl juices or fruit-cun aining gels. Based on the above, the invention relates to basic metal complexes of acidic oligo- and polysaccharides. The metal complexes according to the invention correspond to formula (I) , wherein is an alkaline earth metal ion and/or a transition metal ion with 3<1 orbital, z is the charge number of cation M z+ (i.e. z is equal to 2 or 3) , M τ is an alkali metal ion, Ps~ represents a monomeric unit of the acidic oligo- or poly saccharide chain comprising one carboxylate group, Ps represents one neutral carbohydrate unit of the acidic oligo- or polysaccharide chain, a is the stoichiometric coefficient of the hydroxy ligands, a 2 is the stoichiometric coefficient of the hydrocarbonate ligands, a-, is the stoichiometric coefficient of the carbonate ligand x and y are the stoichiometric coefficients of the individua structural units of the saccharide chain, and n is the polymerization degree of the polysaccharide chain built up from the above structural units, with the proviso that any one of a-^, a 2 and a- may be equal to zero but the sum of a-^, a and a- is always greater than zero, and the maximum value of the sum of a-,, a 2 and 2a- is equal to z-1. The term "acidic oligo- or polysaccharide" as used in the specification and claims refers to oligo- or poly¬ saccharides in which carboxy groups are attached to at least a part of the saccharide monomeric units present. Thus, Ps " in formula- (I) denotes the saccharide monomeric units with carboxylate anions. For polygalacturonic acid Ps~ is a grou of formula (II) . Stoichiometric coefficients a, , a 2 and a, in form (I) indicate the average number of hydroxy, hydrocarbonate and carbonate ligands, respectively, pro one M z+ Ps~ sacchar monomeric unit. Any of stoichiometric coefficients a-,, a- a a- may be equal to zero (in this instance the compound of formula /I/ does not contain the basic ligand in question) , but the sum of a -, , a 2 and a x is always a positive value, an - in accordance with electroneutrality - the sum a-,+a 2 +2a^ may not exceed z-1. If a compound of formula (I) contains only hydroxy groups as basic ligands and they are present i the maximum possible amount, i.e. a, = z-1, and the poly¬ saccharide component is polygalacturonic acid, the structur of the monomeric units comprising a bivalent metal ion corresponds to formula (III) , and the structure of monomeri units comprising a trivalent metal ion corresponds to formu (IV). The formulae of the metal ion-containing monomeric units of the compounds of formula (I) comprising as basic ligands only hydrocarbonate or carbonate ligands in the maximum possible amounts can be drawn similarly. If the value of the difference z - (a- j _+a +2a_.) is a fraction betwee ___+ 1 and 2 (for trivalent M metal ions a fraction between 1 and 3) this means that basic ligands are attached only to a part of metal ions Mz+ present in the molecule; the remaini M z+ ions link two or three polysaccharide chains e.g. as shown in form lae (V) , (VI) or (VII) , Preferred representatives of the compounds of formu (I) are those wherein the value of sum a-,+a 2 +2a, is 0,7 (z-1) or greater, i.e. in which basic ligands are attached to at least 70 % of the M z÷ metal ions present in the molecule, Stoichiometric coefficient x in formula (I) indi¬ cates the average number of acidic saccharide monomeric unit comprising a carboxylate anion neutralized with an alkali metal ion (i,e. s saccharide monomeric unit of formula Ps~M + ) pro one z Ps~ acidic saccharide monomeric unit. Depending o the preparation conditions, in particular, on the molar rati of the alkali metal compounds to two- or trivalent metal compounds, the value of x in the compounds of formula (I) ca be adjusted to any pre-determined value, and even compounds of formula (I) with x equal to zero can be prepared. In the compounds of formula (I) alkali metal ion M + present in the acidic saccharide monomeric units Ps~M' is preferably ' . potassium, and x is preferably less than one. Stoichiome ric coefficient y in formula (I) indicat the average number of neutral saccharide monomeric units (Ps) pro one M z+ Ps "" acidic saccharide monomeric unit. The number of neutral saccharide monomeric units depends on the chemical nature of the starting oligo- or polysaccharide; thus, in principle (for a polysaccharide comprising only acidic saccharide monomeric units) , the value of y may be zero. The neutral saccharide monomeric unit may be e.g, a galεctose unit. Symbol M z in formula (I) covers, in addition to the alkaline earth metal ions and transition metal ions with . orbital, the positive ions composed of transition metal ions and oxygen atoms, such as the VO 2+ ion, too. In formula (I) Ps " may represent e.g. a galacturonate glycuronate, alginate or hyaluronate unit. The invention also relates to a method for the prepa tion of a metal complex of formula (I), According to the in vention one proceeds as follows: a) the alkali metal salt of the starting acidic oligo or polysaccharide is reacted, preferably directly in the rea tion mixture where it is formed, with a salt of a metal ion M z+ formed with an inorganic anion or with a complex of a metal ion M of lower stability constant than that of the acidic polysaccharide - metal ion complex, formed with an organic ligand, the reaction being performed (i) for the introduction of a bivalent metal ion M z+ in the presence of 0.1-1.1 molar equivalents of an alkal metal hydroxide, carbonate and/or hydro carbonate calculated for one molar equivalent of the starting oligo- or poly¬ saccharide alkali metal salt, or (ii) for the introduction of a trivalent metal ion M + in the presence of 0.1-2.1 molar equivalents of an alkal metal hydroxide, carbonate and/ or hydro carbonate calculated for one molar equivalent of the starting oligo- or poly¬ saccharide alkali metal salt, and said salt or complex of metel ion M is utiliz in an amount of 0.7-1.1 equivalents calculated for the total amount of alkali metal compounds present; or b) the starting oligo- or polysaccharide is reacted either as such or as its ester or partial ester, with the oxide, hydroxide, carbona e or hyάrocarbonate of metal ion M z+ to be introduced, said compound of metal ion M z+ being applied (i) for the introduction of a bivalent metal ion M z+ in an amount of 0,55-1 metal atom calculated for one carboxy group or esterified carboxy group present, or (ii) for the introduction of a trivalent metal ion M z+ in an amount of 0,36-1 metal atom calculated for one carboxy group or esterified carboxy group present, and, if desired, any esterified carboxy group presen is saponified with an alkali metal oxide, hydroxide, hydro- carbonate or carbonate. The oligo- or polysaccharide alkali metal salt utilized as starting substance in method a) is prepared either from the acidic (-C00H containing) oligo- or poly- saccharide or from the natural precursor of the acidic oligo or polysaccharide which contains the -COOH groups as methyl esters. This latter method is particularly preferred. Of the natural precursors pectin is mentioned as an example, which is a natural polymer built up from methyl galacturonate units. The alkali metal salt of oligo- or polysaccharide, obtained upon the saponification of the ester groups of the precursor with an alkali metal base, is preferably not isola ed from the reaction mixture, but is reacted directly, in th presence of a further amount of an alkali metal hydroxide, carbonate and/or hydrocarbonate , as defined in points a(i) or a(ii) above, with the salt or complex of low stability ___" * constant comprising the me tal ion M to be introduced. Of the salts of metal ion 3_T , those formed with mineral acids , such as the chlorides and sulfate s , are preferred. Of the complexes of metal ion M z+ with low stability constant, the acetates are to be mentioned. In this method, by varying the amount of the salt o complex of low stability constant comprising metal ion M , the ratio of structural units comprising me al ion M z+ (M z+ to structural units comprising M alkali metal ions (M Ps " ) can be adjusted in the product to any pre-deter ined value. When the salt or complex of low stability constant comprisi metal ion M z+ is applied in an amount corresponding to or close to the upper limit given above, a product comprising only a small amount of M + Ps " structural units (i.e. a com¬ pound of formula /I/ with x much less than one) is obtained Upon decreasing the amount of the salt or complex of low stability constant comprising metal ion M , the proportion of M + Ps~ structural units increases. Similarly, by varying the amount of alkali metal hydroxide, carbonate and/ or hydrocarbonate, the value of difference z - can be adjusted in the product to any pre-determined value. The greater the amount of alkali metal hydroxide, carbonate and/or hydrocarbona e utilized, the closer the value of the above difference to one, i.e. the greater the proportion of structural units of the types shown in formulae (III), (IV) and (VII) among the structural units comprising metal ion M and the smaller the proportio of structural units shown in formulae (V) and (VI) , It should be noted that in this method salts or complexes with low stability constant of more than one metal ion M z+ can also be applied. In this instance complexes comprising two or more bi- or trivalent metal ions M z+ (op- tionally together with alkali metal ions) in one and the same molecule are obtained. It has been observed that the biological effects of such complexes comprising two or more essential metal ions linked to one and the same molecule is much more advantageous than those of the physical mixtures comprising only a single type of an essential metal ion M z+ , In these "multimetal complexes" the ratio of the individual metal ions M can be adjusted to any desired value upon the appropriate choice of the ratio of the starting metal salt or metal complex reactants and by adjusting the pH, the temperature and the ionic strength of the reaction mixture to the appropriate values. In this way complexes with metal compositions most suitable to treat a given disease or dis¬ order can be obtained. Multimetal complexes can be used to great advantage e.g. in the treatment of anaemia, since in this way all of the essential metal ions required in the treatment (iron, copper, cobalt, manganese, zinc, nickel, chromium, magnesium and potassium) can be introduced into the organism as a single composition. The alkali metal salt formed in the reaction can be removed from the resulting compound of formula (I) by aqueous washing. According to method b) of the invention the acidic oligo- or polysaccharides themselves, their natural (fully esterified) precursors or the partial esters formed upon the partial hydrolysis of the natural precursors can equall be applied as starting substances. If only or mainly tri- valent metal ions __. are to be introduced, it is preferred to apply fully or almost fully hydrolysed starting substanc i.e. starting substances without esterified carboxy groups or with esterified carboxy groups only in small amounts. T starting substance is reacted with the oxide, hydroxide, c bonate or hydrocarbonate of the me al ion M to be intro- duced in an aqueous medium. In some instances the reactant (e.g. the metal oxide or hydroxide) can be formed directly in the reaction medium from the appropriate me al. Like method a), method b) can also be applied to form multimeta complexes. When a multimetal complex is to be prepared by utilizing metal reactants with different reactivities, the reactants are added to the reaction mixture in the order o increasing reactivity (i.e. first the less reactive and last the most reactive compound is introduced) , If desired, any esterified group present in the molecule can be saponified with an alkali base after the introduction of metal ions M , whereupon structural units M + Ps " are formed in the resulting compound of formula (I) , If the molecule still contains esterified carboxy groups which are not saponified, these structural units with ester fied carboxy groups are regarded as neutral saccharide structural units (Ps) in formula (I) . Consequently, in method b) the ratio of the individual structural units can be varied by the appropriate selection of the esteri icatio degree of the starting substance, by varying the amount of the compound comprising metal ion M z+ and by subjecting or not subjecting the product to subsequent saponification. An advantage of method b) over method a) is tha no by-product to be removed (alkali metal salt) is formed. Some metal ions, such as Cu ions, are, however, difficult to introduce into the polysaccharide molecule by method b) , since the reactivity of the respective reactant (such as CuO is too low. Therefore, to introduce such metal ions into the molecule, it is preferred to apply method a), The compounds of formula (I) can be converted into pharmaceutical or veterinary compositions by well known phar macotechnological methods, utilizing conventional pharma¬ ceutically acceptable carriers, diluents and/ or other auxili agents. These pharmaceutical or veterinary compositions are also within the scope of the invention. As mentioned above, the invention also relates to fruit and vegetable juices supplemented with an essential metal ion source. The fruit and vegetable juices according to the invention comprise, beside sugar or an artificial sweetener and any optional usual additive (such as water, a preservative, etc.), a compound of formula (I) in an amount of 0.1-1 % by weight calculated for the total weight of the mixture . It has been observed that the compounds of formula (I) not only provide an essential metal ion source, but also exert a favourable consistence-improving and stabilizing effect on the fruit and vegetable juice. In the presence of a compound of formula (I) the sedimentation of fibres from fibrous juices becomes considerably slower, and a beverage with pleasant "full" taste is obtained. These observations are particularly surprising in the light that the compounds of formula (I) themselves are sparingly water-soluble. This stability-increasing effect of the compounds of formula (I) can be attributed presumably to the fact that the basic ligands coupled to metal ions M z (i.e. the hydroxy, carbonate or hydrocarbonate groups) ente into chemical reactions with the weak acids present in frui and vegetable juices (such as malic acid, tartaric acid, succinic acid, etc.). The -OH anions attached to metal ions M z+ are also able to form hydrogen bonds. As a net result o these reactions the oligo- or polysaccharide metal complexe of formula (I) convert into protective colloid-like substan which do not segregate from the beverages and also impede the sedimentation of other floating particles (e.g. fibres) It is also particularly surprising that from these protecti colloid-like substances with metal bridges in their structu the essential metal ions liberage quickly, easily and fully under biological conditions. On the b3εis of the experiences on the metabolism conditions of polygalacturonate metal complexes disclosed in Hungarian patent No. 172,831, one ha to conclude that if the small basic ligands attached to the metal ions M z+ are replaced by bulky acidic organic groups, this ..ould considerably slow down or even stop the transport of metal ions into the living organism. The term "fruit and vegetable juice" as used in the specification and claims covers all kinds of beverages comprising natural fruit or vegetable juice or pulp, op¬ tionally together with a diluent (such as water) or option- ally enriched with carbon dioxide. The fruit and vegetable juices supplemented with an essential metal ion source are prepared according to the in¬ vention in such a way that fruit juice, fruit pulp, vegetabl juice and/or vegetable pulp is admixed, either under aseptic conditions or in the presence of ε preservative, with sugar or an artificial sweetener, with a compound of formula (I) and optionally with one or more conventional additives (such as water, flavouring agent/s/, colouring agent/a/, etc.) . Considering that the compound of formula (I) introduced reac with the v/eak fruit acids present in the beverage, it is som times necessary to add an organic acid in order to adjust the pH of the juice to the pre-determined value and to ensure the required harmonic flavour. Citric acid cannot be applied as organic acid, since it forms a very stable complex with metal ions from which they cannot liberate under biological conditions. Thus, if necessary, it is preferred to add malic acid or tartaric acid to the juices supplemented with a com¬ pound of formula (I) , The invention also relates to fruit-containing gels supplemented with an essential metal ion source. These fruit -containing gels comprise as gellifying agent a 10:1 - 1:10 w/w mixture of a compound of formula (I) and of a conven¬ tional gellifying agent, The term "fruit-containing gel" as used in the spe¬ cification and claims covers fruit jellies, jams and all other gel-like fruit products, too. As known, such fruit-containing gels are prepared by adding a gel-forming agent to the mixture of fruit pulp, sugar, water and other optional additives (such as artificia sweeteners, preservatives, colourants, etc.) in order to provide the required gellous consistency. To prepare fruit- containing gels with low sugar and high water content (x^e- commεnded generally for diabetic persons) usually carragerst are utilized as gel-forming agents, which are sulfated (i.e -SO-H containing) polysaccharide derivatives. The most fre quent gel-forming agent applied to prepare gels with high sugar end low water content is pectin, which is a polygalac uronεte derivative comprising neutral sugar molecules in th polymeric; chain and bearing various side chains attached to the sugar -OH groups, wherein all of the carboxy groups are present as methyl esters. It has been observed that the compounds of formula (I) can be applied not only as essential metal ion supple¬ ments for such fruit-containing gels but, owing to their good gel-forming properties, they can also replace a part (10 to 90 ;•_) of the conventional gel-forming agents utilize in the preparation of fruit-containing gels. Fruit-conta ini gels comprising a compound of formula (I) are more elastic and more stable than those comprising only conventional gel -forming agents, and they contain all the essential ions in a form easily transportable to the living organism. These observations are rather surprising. If Ps " in formula (I) represents a galacturonic acid unit, a com¬ pound of formula (I) can be regarded as a pectin analogue which does not comprise the structural elements of pectin essential for gel formation (i.e. the methyl groups attache to the carboxy groups and the side chains attached to the sugar -OH groups). On this basis no gel-forming effect was to expected from the compounds of formula (I) . On the other hand, compounds of formula (I) comprise basic anions (hydr¬ oxy, csrbonate and hydrocarbona e ions) attached to metal ions M z+ , The excellent consistency-improving (gellifying) effect of the compounds of formula (I) and the high compat¬ ibility of these compounds with fruit-containing gels can be a ttributed pre sumably to the fact that , as mentioned before , the basic ligands attached to metal ions M z+ enter into chemical reactions with the v/eak acids present in fruit-con¬ taining gels , with the -SO^H groups of carragenates or with the free acidic groups of pectin applied as gelling agents. The -OH anions attached to me tal ions M + are also able to form hydrogen bonds. As a net result of these interactions , an elastic, cross-linked gel-forming system is obtained. It is also particularly surprising tha t from this cross-linked gel-forming system the essential metal ions libera te quickly easily and completely under biological conditions , since , as mentioned above , one had to expect a considerable retarda- tion or even stopping of the transport of me tal ions into the living organism. The fruit-containing gels supplemented with an essen tial metal ion source are prepared according to the inventio in such a way that fruit pulp is admixed warm, either under aseptic conditions or in the presence of a preservative , with sugar, water, a gelling agent and optionally with one or more conventional additive (s) , and the mixture is allowed to cool . According to the invention a 10:1 to 1:10 w/w mix¬ ture of a conventional gelling agent and of a compound of formula (I) is utilized as gelling agent . As mentioned above, it is sometimes necessary to add an organic acid to the fruit-containing gel, since the com¬ pound of formula (I) introduced reacts with the weak fruit acids present , O r ganic acids other than citric acid can be applied for this purpose, since citric acid would form a very stable complex with the metal ions present, stopping thereby the metal ion transport to the- living organism. The invention is elucidated in detail by the aid of the following non-limiting Example s. Example 1 Preparation of basic copper (II) -polygalacturonate 10 g of pectin (Genu X-6866 type obtained from Den mark, total acidic capacity: 3,88 x 10~ ? mole/g, degree of esterification: 72,6 ) are hydrolysed in distilled water with 4.35 g (7,76 x 10 — " 2 mole) of potassium hydroxide, and then a solution of 9,69 g (3.88 x 10 "2 mole) of CuS0„.5H o 0 in distilled water is added. The resulting basic copper (II) - polygalacturonate gel is filtered off, washed with distilled water and dried. 12.5 g of the title compound are obtained with a dry substance content of 82,4 % by weight. Analytical data: Theoretical, % 19.55 31.66 3.81 44.99 Preparation of basic chromium( III) -polygalacturonate 10 g of pectin with the quality given in Example 1 are hydrolysed with 6.56 g (1.17x10 " mole) of p.ot.assium hydroxide in distilled water, and then a solution of 10,59 g (5,9xl0 "2 mole) of C Cl 5 ,6H 2 0 in distilled water is added to the mixture. The resulting basic chromium( III) -polygalacturon ate gel is filtered off, washed with distilled water and drie 12,72 g of the title compound are obtained with a dry sub¬ stance content of 87.45 % by weight. Analytical data: Found, % Theoretical, % Cr 15,97 15.73 2.69 C 25.94- 31.13 H 4,95 4.05 IT 1,54 Cl 0.33 Example 5 Preparation of basic iron (III) -polygalacturonate 15 g of pectin with the quality given in Example 1 are hydrolysed with .85 g (1.755^10 mole) of potassium hydroxide in distilled water, and then a solution of 15.81 g ( 2 ,82x10 mole) of FeCl-.6H 2 0 in distilled water is added to the reaction mixture. The resulting basic iron( III) -poly¬ galacturonate gel is filtered off, washed with distilled water and dried, 16,4 g of the title compound are obtained with a dry substance content of 91,20 % by weight. Analytical data: Found, % Theoretical, % Fe 16.78 16.70 0.28 C 27.75 30.78 H ' 4.48 4.00 0 48.80 48.52 N 1.55 Example 4 Preparation of basic manganese (II) -coppe (II)- zinc (II) -polygalacturonate 6 g of pectin (total acidic capacity: 3.74x10 " ^ mole/g) are hydrolysed with 1,889 g (5.56xlO " ' :: mole) of potassium hydroxide in distilled water, and then 0.698 g (5.049X10 " - 5 mole) of potassium carbonate are added to the mixture. The resulting mixture is vigorously stirred, and a homogeneous solution of 1.677 g (6.841x10 " ^ mole) of H (CH 5 COO) 2 .4-H2θ, 0.923 S (3«697xlO~ 5 mole) of CuS0 .5H 2 0 and 3,100 g (l,078χl0 "2 mole) of Zn30 .7H 2 0 in distilled v/ater is added. The metal salt solution comprises the meta ions in a weight ratio of Mn : Cu : Zn = 8 : 5 : 15. The resulting gel is filtered off, washed with distilled water s nd dried. 6.55 g of the title compound are obtained with a dry substance content of 3.5 - % by weight. Analytical data: Theoretical, % 5.26 3.29 32,52 3,85 45,42 Example 5 Preparation of basic magnesium-polygalacturonate 22.3 g of pectin with the quality as given in Example 1 are reacted, under intense stirring, with 3«33 g (8.25xlO~ mole) of magnesium oxide in distilled water. The resulting basic magnesium-polygalacturonate is filtered off and dried. 26,7 g of the title compound are obtained with a dry substance content of 90.43 % by weight. Analytical data: Found, % Theoretical, % Mg 3.28 8,51 C 30.39 56.00 0 4-.04 51.16 Example 6 Preparation of basic calcium-polygalacturonate 2.11 g of pectin with the quality as given in Example 1 are reacted, under intense stirring, with 0.437 g (7.8x10 " ^ mole) of calcium oxide in distilled water. The resulting basic calcium-polygalacturonate is filtered off and dried. 2.57 g of the title compound are obtained with a dry sub¬ stance content of 99,79 % by weight. Analytical data: Ca C H 0 Example 7 Preparation of basic calcium-magnesium-polygalacturo 2.11 g of pectin v/ith the quality as given in Exampl are reacted, under intense stirring, with O.I56 g (1.56x10 " mole) of calcium carbonate and then v/ith 0.252 g (6.24x10 " -^ mole) of magnesium oxide in distilled water. The resulting basic magnesium-calcium-polygalacturonate is filtered off a dried, 2.56 g of the title compound are obtained with a dry substance content of 88.16 % by weight, Analytical data: Theoretical, % 6,73 2.77 35.61 50.60 Preparation of lithium-sodium-potassium-containing ba si c ma gne sium-ca lc ium-polyga la c tur ona te 2.11 g of pectin with the quality as given in Example are reacted, under intense stirring, v/ith 0.105 g (2.6x10 " ^ mole) of magnesium oxide and 0.146 g (2.6x10 " -^ mole) of calcium oxide in distilled water. Thereafter 0.0364 g (8.667x10"^ mole) of LiOHoH-,0, 8.667x10 " ^ mole (0.0486 g) of potassium hydroxide and 0.0347 g (8,667x10 ' mole) of sodium hydroxide are added, and the reaction is continued. The resulting product is filtered off and dried. 2.46 g of the title compound are obtained with a dry substance content of 37.65 r;- by weight. Analytical data: 'Found, % Theoretical, % Mg 2,93 2.84 Ca 4.84 4.69 Li 0,27 0,27 Na 0,92 0,90 1.57 1.52 C 51,21 36.11 E 5.31 4.22 C 50.95 49.44 1. 2.00 Example 9 Preparation of basic magnesium alginate 0.2192 g of alginic acid (an acidic polysaccharide consisting of D-mannuronic acid units, acidic capacity: 4.64x1c " - 5 mole/g) is reacted in distilled water, under intense stirring, with 3.8062 (9.4-124x10 " mole) of magnesi oxide. The resulting basic magnesium alginate is filtered of and dried. 0.3127 g of the title compound are obtained with a dry substance content of 90.70 % by weight. Analytical data: Mg C E 0 N Example 10 Preparation of fibrous pear juice The following substances are applied to prepare 4 litr of fibrous pear juice: 1 kg of pear pulp (pH = 3.96) 0,25 kg of sugar 0.01 kg of malic acid 0.154 kg of basic magnesium-polygalacturonate suspension (dr . 7 substance content: 10 % by weight, the suspen sion contains 1600 mg of magnesium) 20 ca? of a 20 w/v % aqueous sodium benzoate solution 2,59 kg of water The pear pulp is admixed with water, and then the suga the basic magnesium-polygalacturonate suspension and the malic acid are introduced under intense stirring, \7hen the dissolution of sugar is complete the sodium benzoate solutio is added, and the resulting juice is bottled. 0.5 litre of the resulting fibrous juice contains 200 mg of magnesium; the final pH of the juice is 3,8, Example 11 Preparation of fibrous peach juice The following substances are applied to prepare 6.5 litres of fibrous peach juice: 1,6 kg of peach pulp (pH = 3.9) 0.32 kg of sugar 0,016 kg of malic acid 0.205 kg of basic magnesium-polygalacturonate suspension (dry substance content: 10 % by weight, the suspen¬ sion contains 1300 mg of magnesium) 5 ,76 g of potassium sorbate (a 20 w/v % aqueous solution) 4.25 kg of wa ter The fruit pulp is admixed v/ith water, and then the sugar, the basic magne sium-polygalacturonate suspension and the malic acid are introduced under intense stirring . T/hen the dissolution of sugar is comple te the potassium sorbate solution is added, and the re sulting juice is bottled. 0,5 litre of the resulting fibrous juice contains 100 mg of magnesium; the fina l pH of the juice is .5. Example 12 Preparation of cherry n ' e lly enriched with basic magnesium polygalacturonate The following components are applied t o prepare 100 kg of cherry jelly: 82.5 kg of cherry pulp 10.5 kg of ba sic magnesium-polygalacturonate suspension (dry substance content : 10 % by weight , the suspension contains 100 g of magnesium) 0,35 kg of carragena te (Genuel UE quality) 0,1 kg of potassium sorbate (as a 20 v//v % aque ous solu¬ tion) 8.35 k of sugar The cherry pulp is warmed to 80-85°C and the sugar is added. When the dissolution of sugar is complete , the aqueous potassium sorbate solution, the aqueous suspension of basic magnesium-polygalacturonate and then the carragena are added under intense stirring. Af ter 5-15 minute s of stirring the viscous mixture is filled into jars at 60°C .

Claims: What we claim is 1. A metal complex of formula (I), wherein M is an alkaline earth metal ion and/ or a transition metal ion with 3d. orbital, z is the charge number of cation M z+ (i.e. z is equal to 2 or 3), M + is an alkali metal ion, Ps " represents a monomeric unit of an acidic oligo- or poly¬ saccharide chain comprising one carboxylate group, Ps represents one neutral carbohydrate unit of an acidic oligo- or polysaccharide chain, a, is the stoichiometric coefficient of the hydroxy ligands, a 2 is the stoichiometric coefficient of the hydrocarbonate ligands, a, is the stoichiometric coefficient of the carbonate ligands x and y are the stoichiometric coefficients of the individual structural units of the saccharide chain, and n is the polymerization degree of the polysaccharide chain built up from the above structural units, with the proviso that any one of a-, , a 2 and a-, may be equal to zero but the sum of a, , a and a-, is alv/ays greater than zero, and the maximum value of the sum of a-, , a 2 and 2a -_? is equal to z-1. 2. A process for the preparation of a metal complex of formula (I), wherein M z+ , z, M + , Ps " , Ps, a-,, a 2 , a,, x, y and n are as defined in claim 1, characterized in that a) an alkali metal salt of an acidic oligo- or poly ¬ saccharide is reacted, preferably directly in the reaction mixture where it is formed, v/ith a salt of a metal ion M z+ formed with an inorganic anion or with a complex of a metal ion M z÷ of ' lower stability constant than that of the acidic polysaccharide - metal ion complex, formed with an organic ligand, the reaction being performed (i) for the introduction of a bivalent metal ion M in the presence of 0,1-1,1 molar equivalents of an alkal metal hydroxide, carbonate and/or hydrocarbonate calculated for one molar equivalent of the starting oligo- or poly¬ saccharide alkali metal salt, cr (ii) for the introduction of a trivalent metal ion M z+ in the presence of 0.1-2.1 molar equivalents of an alkal metal hydroxide, carbonate and/or hydrocarbonate calculated for one molar equivalent of the starting oligo- or poly¬ saccharide alkali metal salt, and said salt or complex of metal ion M is utilize in an amount of 0.7-1,1 equivalents calculated for the total amount of alkali metal compounds present; or b) an acidic oligo- or polysaccharide is reacted, either as such or as its ester or partial ester, v/ith the oxide, hydroxide, carbonate or hydrocarbonate of metal ion M to be introduced, said compound of metal ion being applied (i) for the introduction of a bivalent metal ion M z+ in an amount of 0,55-1 metal atom calculated for one carboxy group or esterified carboxy group present, or (ii) for the introduction of a trivalent metal ion M z+ in an amount of 0.56-1 metal atom calculated for one carboxy group or esterified carboxy group present, and, if desired, any esterified carboxy group presen is saponified with an alkali metal oxide, hydroxide, hydro¬ carbonate or carbonate. 3. A pharmaceutical or veterinary composition compri ing as active ingredient a compound of formula (I), wherein M z+ , z, M + , Ps " , Ps, a-,, a-,, a,, x, y and n are as defined in claim 1, together with a conventional pharmaceutically acceptable carrier, diluent and/or other auxiliary agent, 4. A fruit juice or vegetable juice supplemented with an essential metal ion source, characterized by conta ing a compound of formula (I), wherein M z+ , z, M + , Ps " , Ps, a-,, a 2 , a,, x, y and n are as defined in claim 1, in an amount of C.l-1 % by weight, together with fruit or vegetab juice or pulp, sugar or an artificial sweetener, and op¬ tionally one or more conventional additive (s). 5. « fruit-containing gel supplemented v/ith an essen tial metal ion source, comprising fruit pulp, sugar or an artificial sweetener, a gelling agent and optionally one or more conventional additive (s), characterized by containing as gelling agent a 10:1 - 1:10 w/w mixture of a compound of formula (I), wherein M z+ , z, M + , Ps " , Ps, a-^, a 2 , a^, x, y and n are as d * efined in claim 1, and of a conventional gelling agent.

Inventors: KOVACS ZSUZSA, KROEEL DULAY NORA, LAKATOS BELA, SANDOR ZOLTAN, TOELGYES MARGIT, VINKLER PETER, KOVACS, ZSUZSA, KROEEL, DULAY, NORA, LAKATOS, BELA, SANDOR, ZOLTAN, TOELGYES, MARGIT, VINKLER, PETER
Applicants: MTA KOEZPONTI KEMIAI KUTATO IN, MTA KOEZPONTI KEMIAI KUTATO INTEZETE
Application year: 1989
Main classification: C08B37
IPC codes: A23L1, A23L2, C08B37