HU213872B - Oligo- and polygalacturonate mixed complex, pharmaceutical and food compositions containing them, further process for preparing these compounds - Google Patents

Abstract

In general formula (I), Me represents an alkaline earth metal and / or a transition metal, Ps- represents a galactose monosodium, is independently an inorganic and / or organic acid anhydride, which represents the charge number of Xi, ranging from 1 to 10, M is an alkali metal, G is a neural distal saccharide unit, z is the average number of charge (averages) of Me atoms, which is a real number from 2 to 3, q is a + b + 2c + n + a + b + 2c + composed of the stoichiometric coefficients a, b, and m , the value of the bonding heat is from 0.0001 to (z-1) real number, which means the sum of the charge of the anonymous, a, b, and the c value independently of each other is greater than 0 or 0, with its binding, hence the value of + b + 2c is at most z-1,0001, m is 0,0001 to 2, real value x is 0 to 56, y is 0 to 35 real number, and N 'is the quotient of the average mid-dimensionalization (N), which is 2úNú300. The present invention further encompasses pharmaceutical compositions comprising the above compounds, and food growths, as well as a process for the preparation of compounds for the preparation of compounds. ŕ

Description

BACKGROUND OF THE INVENTION The present invention relates to mixed oligo- and polygalacturonate complexes, pharmaceutical compositions containing them, and food compositions. The invention also relates to a process for the preparation of these compounds.

It is known that in treating the deficiencies caused by various macro-, field- and micro-nutrient deficiencies and vitamin deficiencies, not only one, but also several essential nutrients, elements, or ions, vitamins and essential amino acids are required at the same time, since they are often synergistically amplified. It was first recognized the synergistic effect of magnesium and vitamin B ₆ [J. Durlach, J. Med., Besancon, 5,349-359 (1969); P. Fr. M. 8058 (CL A 61k); CA 77. 39245y], For a more beneficial effect, the magnesium vitamin Bg complex was supplemented with amino acids (glycine, glutamic acid) [DL Leussing and N. Sister: Anal. Chem. 38, 1388-1392 (1966); R. Kristen et al., Eur. J. Clin. Pharmacol. 34: 133-137 (1988)].

DE OS 2 006 967 and Perfume. Cosmet., Savons 8 (3), 113-23 (1965) - CA. 63, 4096 (1965) discloses aluminum allantoin polygalacturonate complexes for cosmetic and dermatological purposes. These complexes belong to the group of compounds of the acidic polysaccharides. These known products are not suitable for oral and food applications, as aluminum has recently become known for its many health effects. A disadvantage of the production technology of this disclosure, both economically and environmentally, is that the reaction product must be recovered from the reaction mixture by filtration and washing.

DE OS 2 649 406 discloses calcium salts of a group of compounds of the low-esterification pectin acid and their use as a gelling agent. These pectates are characterized by the fact that calcium and other polyvalent metals are attached to galacturonic acid units with all their valencies. Due to a pH of up to 5 which can be used in the process, a significant proportion of the pectin -COOH groups remain in the free acid form, which is uneconomic for the introduction of essential elements into the body. A further disadvantage of the process is that the product is recovered from the reaction mixture by addition of alcohol, precipitation and filtration.

U.S. Pat. No. 4,689,322 discusses the therapeutic use of neutral calcium salts of polymeric uronic acids and also salts thereof with some essential metals. The purpose of the therapeutic application is to bind phosphate and oxalate ions in the body and not to deliver anions of essential elements (P, Se) or medicinal acids in anionic form to the human body.

U.S. Pat. No. 5,089,606 discloses the therapeutic use of water-insoluble hydrogel foams with acidic polysaccharides with divalent or polyvalent metals for the treatment of pre-and post-operative disinfection of body orifices. Immediately after use, they develop carbon dioxide reactions leading to the formation of a cross-linked (neutral) metal alginate gel and formation of a foamy structure.

Under the reaction conditions described, no structural units may be formed in which an anion of a therapeutic acid is attached to the acidic polysaccharide via the action of a divalent or polyvalent metal. These hydrogel foams should not be used as oral formulations.

U.S. Pat. No. 2,871,236 discloses mixed metal complexes with polygalacturonate complexes in which a portion of the carboxylate ions of the polygalacturonic acid is attached to the cation of an organic base (drug) rather than a metal ion. The "mixed" nature of these mixed complexes is thus given by the various types of cations (metal cations and amine-base cations) attached to the carboxylate anions of the galacturonate units.

The basic metal complexes of acidic oligo- and polysaccharides produced by the process of Hungarian Patent No. 203,365 release biological ions at an accelerated rate under biological conditions and transfer all of their metal ion content in bioavailable form to living organisms.

There is a need for formulations that provide effective delivery of several different types of essential substances (elements, vitamins, amino acids, and the like) at the same time based on the optimal management of various deficiency states. At the same time, it is desirable to have as carriers for pharmaceutical formulations and foods substances that provide a more effective release of the active ingredients or nutrients.

SUMMARY OF THE INVENTION It is an object of the present invention to provide mixed complexes which contain, in addition to metal cations of interest to the body, essential anionic materials, such as vitamins, amino acids, and therapeutically active compounds, in a chemically bound form and with high efficiency.

The present invention is based on the discovery that both the cationic and anionic constituents can be chemically bonded to the novel compound complexes of formula (I), while being highly available to the body during the metabolic process. Thus, the object of the present invention is achieved by the compositions of the invention.

Accordingly, the present invention provides mixed oligo- or polygalacturonate compounds of formula (I)

HO - [{Me ^{z +} (Ps ~) zq (OH) a (HCO3 -) b (CO3 ² -) c (X ^ · ^- ) »} (M ⁺ P _S -) _x G _y ] _N -H (I ) in which formula

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Me represents an alkaline earth metal atom and / or a transition metal atom,

Ps "means galacturonate,

X ¹ ' ¹ is independently an anion of an inorganic and / or organic acid having therapeutic and / or beneficial physiological activity, wherein n, X, represents the charge number of an anion having an integer from 1 to 10,

M is an alkali metal,

G is the neutral saccharide unit free of the carboxylate group, z is the (average) charge number of Me atoms in the mixed complex molecule having a real number from 2 to 3, q is the stoichiometric coefficient of a, b, c and m Σ ⁿ , m, expression, with the proviso ai = l that its value is a real number from 0.0001 to (zi),

1000 where Σ njmj is the mixed complex molecule = 1

The sum of the charge anions Xj '' in Ia, a, b, and c, independently, is a real number greater than 0 or 0, provided that + b + 2c is at most z-1.0001, m is 0, 0001 to 2 is a real number, x is a real number from 0 to 56, y is a real number from 0 to 35, and Ν 'is the average degree of polymerisation (N), which is: 2 <N <300th

Thus, the compound complexes of the present invention are metal oligo- and polygalacturonate complexes containing at least two anions. In contrast to the mixed complexes disclosed in U.S. Patent No. 2,871,326, the mixed complexes of the present invention are characterized by the mixed nature of the mono-, di- and / or trivalent metal ions attached to the galacturonate anions of the oligo- and polygalacturonic acid, and organic and divalent metal ions. / or anions of inorganic acid (s).

In the compound complex of the invention

Mez + can mean, among others, Mg ²⁺ , Ca ²⁺ , Sr ² *, Cr ³⁺ , Mn ²⁺ , Fe ²⁺ , Fe ³⁺ , Co ²⁺ , Co ³⁺ , Cu ²⁺ , Zn ²⁺ , Ni ²⁺ , Ga ³⁺ . Me2 ^{+ can} also mean cations consisting of transition metals and oxygen atoms, such as (vanadyl) cation VO ²⁺ .

In these mixed complexes, the oligo- or polygalacturonic acid is a carrier, both chemically and physically, of the metal ions directly attached to the carboxylate groups and of the X 1 'anions derived from the acids H _ni Xi via the divalent or trivalent metal ions; hereafter referred to as a carrier. In mixed complexes of this type, the carrier can be any acidic oligo- or polysaccharide such as alginic acid, carboxyl cellulose and carrageenan. Acid polysaccharides which are commercially available at relatively low cost and in constant quality are of greatest practical importance for the compound complexes of the present invention. Of the acidic polysaccharides, natural pectin of plant origin has the greatest practical importance, being partially methylesterified polygalacturonic acid (ML Fishman and JJ Jen, Chemistry and Function of Pectins, Am. Chem. Soc. Symposium Series 310, Washington, DC, 1986),

The object of the present invention is thus achieved by the use of mixed oligo- and polygalacturonate complexes. Namely, the oligo- and polygalacturonic acid exhibit extremely high selectivity for Ca ²⁺ ions compared to other acidic oligo and polysaccharides, replacing the calcium ions strongly bound to the brush border membranes of the intestine cells and the intestinal feathers by replacing them with the metal ions to be ingested. for efficient absorption of ions [Tamás Fazekas, Béla Selmeczi and Pál Stefanovits: Sources and Significance of Magnesium in the Living World, Akadémiai Kiadó, Budapest, 1992, 283-284],

In the compound complexes of the present invention, the carrier may be an acidic polysaccharide consisting of galacturonic acid moieties, hereinafter referred to as HPs (C 6 H 8 O 2), without indicating the degree of polymerization and the carboxylate group, or one galacturonic acid containing one mole of carboxylate acid or In these mixed complexes, the anion Xj 'of an inorganic and / or organic acid (s) is linked to the galacturonate anion of the support by mediation of divalent and / or trivalent metal ions, i.e., X ¹ ', Ps' Me ²⁺ , Ps-Me ³⁺ or (Ps ^_). 2Me ³⁺ , and the methyl esterified galacturonic acid content of pectin is represented by the formula CH ₃ Ps, which has the same quantitative structure as the former, thus repeating galacturonic acid units in the polymer of the carrier.

In the mixed complexes of the present invention, the average degree of polymerization of the support can range from 2 to 300. The exact determination of the molecular weight of the mixed complexes and the degree of polymerization of the carrier therein is hindered by the difficulty of determining the molecular weight of acidic oligo- and polysaccharide salts of divalent and polyvalent metals (metal complexes). This is generally true for complexes of acidic oligo and polysaccharides which contain even trace amounts of polyvalent metal (s).

Such metal complexes are known to remove traces of doubtful polyvalent metals by repeated washing with a strong mineral acid. The average degree of polymerization of the pure recovered free acid oligo- or polysaccharide can be determined by known methods (gel chromatography, viscometry, light scattering). However, this purification process results, on the one hand, in repeated depolymerization and, on the other hand, in the purification, the smaller or larger fraction of the lowest molecular weight oligomer fraction is lost due to its better solubility. The results obtained do not give the actual average degree of polymerization of the support.

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The average degree of polymerization of samples of the same material, determined by various methods, can be up to 100% or more. Thus, for the average degree of polymerization of a sample, the following results were obtained, respectively, by end group determination, two gel chromatographic determinations, and osmometric determination: 60, 86, 111, 190 [M. L. Fishman and J. J. Jen, Chemistry and Function of Pectins, Am. Chem. Soc. Symposium Series 310, Washington, DC, 1986, page 33]. Different pectin samples as well as polygalacturonic acids recovered from metal polygalacturonates by various methods (light scattering, viscosimetry and gel chromatography) have average molecular weights between 13,000 and 57,000. Kever and NVD Yakonova, Acta Alimentaria, 21, (3-4) 334-349 (1992)] In the process of the present invention, similar chemical effects (pH, 60-90 ° C, reaction time of 4-24 hours, mixing), at least the same degree of depolymerization as in the cited studies, and it can be safely stated that the average degree of polymerization of the carrier in the compound complexes of the invention is in the range of 2-300.

Polymeric molecules of pectic acids also contain (neutral) saccharide units without natural "impurity" carboxylate groups such as L-rhamnose, D-galactose, L-arabinose, D-xylose, D-glucose and Dmannose [Fishman and Jen: Chemistry and Function of Pectins , Am Chem Chem Soc Symposyum Series

310, Washington, DC, 1986, pages 4 and 18]. (In the exemplary embodiments, neutral saccharide content is always given as glucose [(C 6 H 10 O 5]) in the compound complex formulas).

The invention also relates to pharmaceutical compositions. The pharmaceutical compositions of this invention contain as active ingredient a compound of formula (I) wherein Me, Ps ", X, ^1M , G, z, q and q 'and a, b, c, n, m, x and y in addition to the usual pharmaceutical carriers, diluents and / or other excipients described above.

The invention also provides food composition, based on total weight comprising at least one (I) of formula vegyeskomplexet amount from 0.001 to 10% by weight, wherein Me, Ps 'X _s' M, G, z, q and Ν'jelentése and a, b, c, n ;, m, x and y are as defined above.

These food compositions are prepared by adding to the food in a known manner a mixed complex (s) in the form of a dried product or a suspension or solution in a conventional manner for the preparation of a food product, using a 0.001% to 10% w / w mixture.

The invention further provides a process for the preparation of mixed complexes of formula (I) wherein Me, Ps-Xj 'M, G, z, q and Ν' and a, b, c, n "m, x and y are as defined above. . During the procedure

a) a basic metal oligo or metal polygalacturonate of formula II

HO- [{Me- (Ps-) _zq '(OH-) _a (HCO ₃ ) _b (CO ₃ ² ) c} (M ⁺ PS-) _x G _y ] _N. -Η (II)

- in which formula

Me, Ps ^_ , M, G, z, and Ν 'and a, b, c, x and y are as defined above, q' is the a + b + 2c expression of the stoichiometric coefficients a, b and c with the proviso that its value is 0.001 (zl) to a real number (h ⁺ ) '. With an acid of formula Xj ' ¹ wherein Xj ¹ is and n is as defined above, or

b) (H ⁺ ) _n . The acid (s) of the formula Xj ', wherein X ₍ ¹ is and n is the value of Me in the excess metal (s) or compound (Me)), wherein

Me is as defined above, and the compound (s) are (are) oxide (s), hydroxide (s), carbonate (s), bicarbonate (s), or basic carbonate (s). ) by reaction with oligos or polygalacturonic acid or pectin, or

c) reacting a mixture of oligo- or polygalacturonic acid or pectin and ( ^{H +} ) n, Xi ⁿⁱ acid (s) with a metal (s) Me or a compound (s) thereof and optionally obtaining the resulting compound (Η ⁺ ) _an acid of formula _η , Χί ^η 'other than the acid (s) used in process variants a), b) or c) wherein Xj' is n; value above - react.

If desired, the product obtained is isolated in known manner.

In the process variant (a) of the present invention, the starting material used is the basic metal oligo- or polygalacturonate obtained by the process described in Hungarian Patent Application No. 203,365. In these basic metal complexes, the basic OH-ions attached to the divalent and trivalent metal ions may be replaced by carbonate and / or bicarbonate ions in any proportion. Neutral moieties of the formula Me ² + (Ps) 2 and Me ³⁺ (Ps' 3), wherein Me and Ps ~ are as defined above, are also allowed in amounts of from 0 to 95% relative to the total carboxylate content of the support.

The basic metal complex is reacted with an acid or acids of the formula H _n , Xi. This process variant is illustrated by the acid-base reaction of Scheme 1 below, wherein for the sake of simplicity η, = 1, X 1 = X and Me = Mg, the starting compounds are basic magnesium polygalacturonate and a monovalent acid.

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Scheme 1

HO-Mg-Ps + HX - »(X-Mg-Ps · HO-Mg-Ps) + H ₂ O

In process variant b) of the present invention, the acid or acids of the formula H _n , Xi are first reacted with Me (s) Me or their compound (s). An excess of metal (s) or metal compound (s) is used. The resulting reaction mixture (which salts of H _n, Xi formula acid (s) and / or base salts and the metal (s) in excess and / or metal compound (s) included) with the carrier (pectin or pektinsawal) . This embodiment is illustrated in Scheme 2 below (again for simplicity, n = 1, Xi = X and Me = Mg).

Scheme 2

HX + 2 MgO + H ₂ O-> HO-Mg-X + Mg (OH) ₂ , then HO-Mg-X + Mg (OH) ₂ + ₂ HPs->-> (X-Mg-Ps · H Mg-Ps) + ₂ H ₂ O

Essentially, the formation of the mixed complex results in reactions analogous to the above two reactions when the polyvalent H _n , X 1 acid or mixture of acids is reacted with the metal (compound) component (s) and then the resulting compound (s) with the support. The first stage of the reaction, the H _ni Xi acid (s) may also form neutral salts (s) of magnesium (or other metal) as illustrated in Scheme 3.

Scheme 3

HX + 4 MgO + 2H ₂ O-> MgX ₂ +3 Mg (OH) ₂ , then MgX ₂ +3 Mg (OH) ₂ + 4 HPs -> (2X-Mg-Ps · 2 HO-Mg-Ps) + 4 H ₂ O

The use of process variant b) is particularly advantageous when the reactivity of the H _nj Xi acid (s), such as flavonoids or certain amino acids, used in the preparation of the mixed complexes is low.

C) process variant for the preparation vegyeskomplexek reacted acid (s) mixture of the carrier and the formula H _ni Xi with the metal (metals) or a metal compound (metal compounds). This process variant (retaining the above simplification using magnesium oxide and a monovalent acid as the metal component again) is illustrated in Scheme 4.

Scheme 4

HPs + HX + 2 MgO -> (X-Mg-Ps HO-Mg-Ps) + H ₂ O

It can be seen that the three process variants for the preparation of the mixed complexes yield the same end product under the same stoichiometric conditions.

In addition to the process variants a) -c) discussed above, there are many other possibilities for preparing the compound complexes of the present invention by making the compound of formula I obtained by any of the process variants a) -c) different from the acid (s) used. but is reacted with an acid of the formula H _ni Xj, wherein _{n is} given by the j + i relationship.

The above-described combined reaction pathway is particularly useful when it is desired to incorporate a plurality of acids of the formula H _ni Xi in the mixed complex molecule, one of which is more strongly degraded by basic media or at elevated temperatures. Such a combined process variant is illustrated in Scheme 5 with the simplified designations previously used, where Me = Ca. In this case, the mixed complex prepared by process variant b) is reacted with the decomposition acid HXj.

Scheme 5

HX + 4 CaO + 3 H ₂ O- »HO-Ca-X + 3 Ca (OH) ₂ H0-Ca-X + 3 Ca (OH) ₂ + 4 HPs- (X-Ca-Ps 3 HO-Ca- Ps) + 4 H ₂ O (X-Ca-Ps · 3 HO-Ca-Ps) + HXj—> -► (X-Ca-Ps · Xj-Ca-Ps · 2 HO-Ca-Ps) + H ₂ SHE

Such decomposing acids include L-ascorbic acid and acetylsalicylic acid. Therefore, if HX1 in the above example is L-ascorbic acid, then the reaction described in equation 1 is carried out at a higher temperature (up to the boiling point of the reaction mixture) and the reaction in equation 3 is preferably carried out at a lower temperature (room temperature).

Alternatively, the product of Scheme 5 may be prepared starting from the mixed complex of live variant c) as depicted in Scheme 6 by the conventional simplified labeling method.

Scheme 6

HPs + HX + 4 CaO - »- (X-Ca-Ps · 3 HO-Ca-Ps) + H2O, then (X-Ca-Ps · 3 HO-Ca-Ps) + HXj-► (X-Ca- Ps · Xj-Ca-Ps · 2 HO-Ca-Ps) + H ₂ O

Again, the first reaction is suitably carried out at a higher temperature while the second reaction is carried out at a lower temperature.

In the process of the invention, the Me metal (s) is reacted in the form of elemental metal powder, metal oxide, metal hydroxide, metal (bicarbonate) carbonate, basic metal carbonate, basic metal oligo- or polygalacturonate metal.

If metal carbonate and / or bicarbonate are also used in the preparation of the mixed complexes, the (residual) basic OH-ions attached to the metal in the final product may be replaced by (partially) carbonate and / or bicarbonate ions. Carbonates of divalent or trivalent metals may be used as the reaction component when the acid (s) H _n1 Xi is a stronger acid (s) than carbonic acid. However, this condition is usually met.

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The base metal polygalacturonate, pectin and polygalacturonic acid used as starting materials in the process of the invention form a poorly water-soluble colloidal system. Metals and metal compounds used in the mixed complex to produce and H _n, Xi acid (s) do not dissolve or only very slightly soluble in water, so the production of vegyeskomplexek virtually all cases different phase interface by means of reactions occurring heterogeneous occasionally. The starting materials, intermediates, and mixed complex end products are also highly insoluble in organic solvents, so that heterogeneous reactions can be performed even when organic media are used. It will be apparent to those skilled in the art that conducting heterogeneous reactions at rates that are practically acceptable requires appropriately selected reaction conditions. The reaction rate can be favorably influenced by providing high surface area contact, sufficient concentration and appropriate stoichiometric ratios, adequate mixing intensity, sufficient reaction time and appropriate temperature.

H _ni Xi acids are generally non-polymeric, inorganic acids such as HI, HF, H ₂ SeO _3, H ₂ SeO4 and H3PO4 or an organic acid of formula for the introduction of X + Anions - regardless of the acidic nature of their -COOH, -SO 3 H, = HPO ₄ , -H ₂ PO ₄ , phenolic -OH or other groups. However, polymeric acids such as polyphosphoric acid may also be used. In the case of polyhydric acids, their acid salts with various bases (inorganic or organic) as well as partial esters of polyhydric acids such as KHF ₂ , riboflavin-5'-phosphate-Na-salt, pyridoxal-5-phosphate, menadione sulfite may be used. .

These therapeutic and / or beneficial physiologically active, biologically active organic acids may be of natural, semi-synthetic or synthetic origin, which according to their physiological, chemical structure and properties may be classified into the following main groups:

- vitamins,

- flavonoids,

- active pharmaceutical ingredients,

- amino acids, oligopeptides,

- other biologically active organic acids (such as eicosapentaenoic acid) which have a beneficial physiological effect.

The most important representatives of the healing organic acids of natural origin are the acidic components of various herbs or their extracts.

By "curative and / or beneficial physiological effect" is meant the effects known on the application date.

The temperature can be chosen within a wide range (from room temperature to the boiling point of the solvent), but it influences the time required for the reaction to proceed. However, in some cases, such as the use of heat-degradable reagents, including vitamins, this aspect sets the upper limit of the applicable temperature.

The end point of the reactions can be determined by detecting the consumption of one of the reaction components, preferably the least reactive component. Analytical methods for detecting and quantifying various compounds are known to those skilled in the art or can be found in the chemical literature.

The solvent used in the process of the invention is generally water, but may also be a mixture of water and an organic solvent such as ethanol and ethyl acetate. The amount of water required to carry out the reactions depends primarily on the mixer power and the temperature used. The amount of solvent used is generally 10 to 50 times the amount of carrier added to the reaction mixture.

It is also known to those skilled in the art that certain compounds, such as vitamins, are also degraded by the oxygen and / or light in the air. In the preparation of mixed complexes containing such components, these adverse effects are eliminated by the use of inert gas and / or by the exclusion of light. For the drying of mixed complexes containing the decomposing component (s), it is preferable to use lyophilization on an industrial scale rather than spray drying.

In some cases, for example, a ready-to-use compound complex for enrichment of the food product (s) may be used without drying, i.e. the entire reaction mixture (suspension or colloidal solution) is incorporated into the food product (including soft drinks).

In the process of the invention, it is essential to maintain an appropriate stoichiometric ratio of the reaction partners. As illustrated in Scheme 1, the reaction equilibrium can be shifted towards the formation of mixed complexes by using an excess of the basic metal complex according to the law of mass effect. Adverse adverse reactions of the reactant components result in undesirable side-effects.

Such undesirable side reactions result in H _ni Xi acid (s); excess may partially dissolve the metal content of the carrier X 1 -Me-X; during the formation of a salt of the general formula. The likelihood of such side reactions occurring is increased if the acid of formula H _ni Xi forms a complex of high stability with the metal in question relative to the stability constant of the metal or basic metal complex of the support. The stability constants of metal compounds of various organic and inorganic acids can be found in the literature (Douglas D. Perrin, Stability Constants of Metal Ion Complexes, Part B, IUPAC Chemical Data Series No. 22, Pergamon Press, 1979) or by known methods.

1-6. For the sake of illustration, the reaction schemes for divalent metals are included. The formation reactions of the mixed complexes proceed in a similar manner when the starting basic polygalacturonate metal contains a trivalent metal or several bivalent and trivalent metals at the same time, and if the acid (s) of formula H _ni Xi are not monovalent. In these cases, different -Me-X structures of various complexes are linked to galacturonate units of the mixed complex. Determining the exact structure of these

EN 213,872 Β instrumental investigations such as infrared spectroscopy (FT-IR), electron spin resonance (ESR), mass spectrometry (MS), and analytical electron spectroscopy (ESCA). The infrared spectra of the most common absorption bands are summarized in Table 2 for the identification of mixed complexes.

It is clear from the general formula (I) of the compound complexes of the present invention that the presence of alkali metals such as Li, K and Na is allowed. Such alkali metal galacturonate moieties are free of X 1 'anions. However, the role of the alkali metal content is surprisingly great in changing the physical properties of the mixed complexes, in particular the water solubility, since the sufficiently high alkali metal content makes the mixed complex water-soluble. In these mixed complexes, up to 95% of the galacturonate moieties may contain alkali metal cations. The change in physical property (s) results in a minor change in the chemical - and at the same time physiological - properties of the compound complex. Increasing solubility may increase the rate of absorption and the extent of biological (physiological) utilization.

The alkali metal may be used in the form of a hydroxide, carbonate or bicarbonate in the process of preparing the mixed complex. The alkali metal compound in the case of process variant a) H _ni Xi prior to reaction with an acid of general formula (acid) and / or after b) and c) where the variant is suitably administered final reagent to the reaction mixture.

The alkali metal content of a given compound complex which becomes water soluble can be determined experimentally. Water solubility is influenced by several factors, such as the degree of polymerization of the support, the material quality of the 2- and 3-value metals in the complex, their ratio in the case of several metal components, the material quality and quantity of the acid component or acid components of the mixed complex.

The amount of reactive components required to prepare the compound complexes of the present invention is determined by stoichiometric calculations by comparing the amount of reactive carboxylate groups of the carrier (including the esterified carboxylate groups in the case of pectin starting material). X1 'anions can be attached to 0.01 to 100% of the divalent and / or trivalent metal ions in these mixed complexes. In the case of a) eljárásáváltozat amount of a basic metal complex reactive starting material (associated with metals) of basic OH "-ionjainak also serve as a benchmark for calculating the H _ni Xi acid (s) volume.

It is very advantageous that the compound complexes of the present invention can be prepared by three different process variants and, if desired, a combination thereof. This allows for the preparation of the various compound complexes under the most favorable reaction pathway and under the most appropriate reaction conditions, in view of the chemical properties of the reacting components, in particular the acid (s) H 1 X 1. Selection of the appropriate reaction pathway and reaction conditions will be apparent to those skilled in the art.

The process of the present invention does not produce by-products that should be removed by purification processes. This is very beneficial both economically and environmentally.

The invention is further illustrated by the following non-limiting examples.

The starting materials Mg, Fe (II / III), Mn (II) and Cu (II) polygalacturonate used as starting material according to process variant b) described in Hungarian Patent Application 203 365, 5, 3.10 and 1, respectively. and Zn polygalacturonate was prepared in a similar manner to that described above.

In the compound formulas of the herbicidal active compound complexes, all the acidic components of the herb (s) and / or extract of the given example are given as monovalent X1 -. In these examples, the total acid content of the drug or extract in question is expressed in mmol / g or mmol / cm ^{3 as} acid equivalents. In addition, the amount of the 1-2 flavonide components of the extract in question as determined by the methods described in the German Pharmacopoeia (DAB 8) is given.

Unless otherwise indicated, the reaction is carried out in an aqueous medium.

The mixed complex final product is obtained in a dry form by direct lyophilization in a laboratory process and preferably in a spray drying process on an industrial scale.

Example 1

Preparation of mixed magnesium polygalacturonate iodide complex

An aqueous suspension of freshly prepared basic magnesium polygalacturonate (5.00 g, 7.72% Mg) was reacted with 1.885 cm ^{3 of} 57% w / w hydrogen iodide solution (1.701 g / cm ³ ) with vigorous stirring. After the completion of the reaction, the resulting slurry was dried by lyophilization to give 6.87 g of the title compound.

Elemental analysis of the compound complex HO- [Mg ₂ ⁺ (C ₆ H ₇ O ₆ ") (ΟΗ") ο ι (Γ) ο, 9 (C ₆ H ₁₀ O ₅ O ₃ N-H):

found (% by weight) calculated (% by weight) C: 21.76 27.98 H: 4.61 3.19 mg: 5.62 5.88 I: 26.35 27.58

Example 2

Preparation of a mixed complex of magnesium polygalacturonate fluoride

Freshly prepared basic magnesium polygalacturonate from 5.00 g polygalacturonic acid and 0.957 g MgO vi7

In a vigorous agitation, 0.84 cm ³ (40% w / w) of hydrogen fluoride solution was reacted with vigorous stirring. After the reaction, the resulting suspension was dried by lyophilization to give 5.5 g of the title compound.

Elemental analysis of the compound complex HO- [Mg ²⁺ (C ₆ H ₇ O ₆ ) (OH ") _0j 2 (F") 0, 8 (C 0

found (% by weight) calculated (% by weight) 10 C: Found (% w / w) 31.34 calculated (% by weight) 36.99 C: 28.66 34.6 H: 5.57 4.57 H: 4.91 3.70 mg: 5.28 5.44 mg: 9.5 9.62 B: 1.73 1.93 I: 5.6 6.02

Example 3

Preparation of a mixed complex of magnesium polygalacturonate dihydrogen phosphate

Freshly prepared 1.39 g of Mg-containing basic Mg polygalacturonate is reacted with 3.1 cm ^{3 of} 85% phosphoric acid in an aqueous medium with vigorous stirring. The reaction mixture was dried by lyophilization to give 19.6 g of the title compound.

The mixed complex HO- [Mg ²⁺ (C ₆ H ₆ O ₇ ~) (OH) 2 p (H ₂ P0 ₄ ") _i o 8 (CfiH] Analysis for the formula for 0 () 5) amount 0.2 IJN H results:

Found (% by weight) Calculated (% by weight)

C: 23,16 27.75 H: 4.51 3.47 mg: 7.53 7.71 P: 7.82 7.87

Example 4

Preparation of magnesium polygalacturonate selenate mixed complex

3.74 g of freshly prepared 288.7 mg of Mg-based Mg polygalacturonate in aqueous suspension are reacted with 0.763 g (0.005 mol) of 95% w / w selenic acid (H ₂ SeO 4) with vigorous stirring. The reaction mixture was dried by lyophilization to give 4.35 g of the title compound.

Elemental analysis of HO- [Mg ²⁺ (C ₆ H ₇ O ₆ -) (OH) o, 158 (SeO ₄ ² -) o, 421 (C ₆ H ₁₀ O ₅ ) o, 4 ₇₇ ] nH in the mixed complex:

found (% by weight) calculated (% by weight) C: 15.77 31.33 H: 4.45 3.51 mg: 6.64 7.16 Neither: 9.07 9.79

Example 5

Preparation of a mixed complex of magnesium polygalacturonate (fructose) borate

Freshly prepared basic magnesium polygalacturonate containing 474 mg of magnesium was reacted in aqueous medium with the addition of 965 mg of boric acid (Η3ΒΟ3) followed by 2.81 g of fructose under vigorous stirring. The reaction mixture was dried by lyophilization to give 8.94 g of the title compound.

Elemental analysis of the compound complex HO- [Mg ²⁺ (C ₆ H ₇ O ₆ -) (OH-) o, 2 (C ₆ H ₁₀ O ₄ BO 3) o, s (C ₆ H ₁₀ O ₅ ) 0- 497] n ~ H:

Example 6

Preparation of the Magnesium Polygalacturonate L-Ascorbate Mix Complex A freshly prepared basic magnesium polygalactone turonate containing 2.31 g of magnesium polygalacturonic acid in aqueous medium is reacted with 13.39 g of L-ascorbic acid under vigorous stirring. The resulting slurry was freeze-dried to give the title product (42.2 g, 85.6% solids).

The mixed complex

HO- [Mg ²⁺ (C ₆ H ₇ O ₆ -) (OH) o, 2 (C ₆ H ₇ O ₆ -) o, 8 (C ₆ H ₁₀ O ₅ ) o, 214] n - H t

elemental analysis of ascorbate:

found (% by weight) calculated (% by weight) C: 32.99 38.4 H, 4.87 3.96 Mg: 5.42 6.44 Vitamin C: 28.0 36.0 Example 7

Preparation of Magnesium Polygalacturonate Vitamin P (Routine) Mixed Complex

1.013 g of freshly prepared alkaline Mg poligalakturonátot containing 78.2 mg of magnesium was reacted with 1.817 g rutintrihidráttal (C ₂₇ H ₃₀ Oi6-3 of H ₂ O) in an aqueous medium with vigorous stirring. After completion of the reaction, the reaction mixture was dried by lyophilization to give 2.8 g of the title compound.

The mixed complex HO- [Mg ^2, (C ₆ H ₇ O ₆₎ (OH ') o, 15 (C ₂₇ H ₂ 90i6 ~) o, 85 (C ₆ Hio05) p 608] The results of elemental analysis on n -H chemical formula :

found (% by weight) calculated (% by weight) C: 42.5 47.8 H: 5.59 4.63 mg: 2.75 2.97 routine: 58.3 63.3

Example 8

Preparation of magnesium polygalacturonate rutin ascorbate mixed complex from g of polygalacturonic acid, freshly prepared, 346.4 mg

The basic Mg-polygalacturonate containing magnesium containing magnesium was reacted first with 7.71 mg of rutin trihydrate and then with 1.93 g of L-ascorbic acid in an aqueous / alcoholic medium containing 40% by volume of ethyl alcohol. The reaction mixture was dried by lyophilization to give 6.15 g of the title compound.

The mixed complex HO- [Mg ²⁺ (C ₆ H ₇ O ₆ -) {OHjoj (C ₂₇ H ₂₉ O | 6 ') _? OS ₂ (C ₆ H ₇ O ₆ Q 0, 768' • (C ₆ H ₁₀ O ₅₎ 0, 608 ] Results of elemental analysis of n-H ΐ 10 ascorbate:

found (% by weight) calculated (% by weight) C: 35.0 40.78 H 5.1 4.33 mg: 4.9 5.01 routine: 8.1 10.3 Vitamin C: 22.1 27.75 Example 9

Preparation of magnesium-polygalacturonate-vitamin complex mixed g polygalacturonic acid (4.75 mol / kg acid equivalent number) and 191.5 mg of magnesium oxide 25 fresh basic aqueous suspension of Mg polygalacturonate obtained 654.8 mg of vitamin A (retinoic acid: C ₂ oH ₂ g0 ₂ ) in an aqueous medium with vigorous stirring.

The reaction mixture was dried by lyophilization to give 1.69 g of the title compound. 30

The mixed complex HO- [Mg ²⁺ (C ₆ H ₇ O ₆₎ (OH) o 6 (C ₂ oH ₂₇ 0 ₂ ^-) p, 4 (C6Hio0 ₅ "), p, 214] n Analysis for H sum formulas :

found (% by weight) calculated (% by weight) C: 44.53 50.43 H: 6.35 5.65 mg: 6.38 6.68 Vitamin A: 30.2 32.9

Example 10

Polygalacturonate magnesium adenosine triphosphate (di-

sodium salt) found (% by weight) calculated (% by weight) Freshly prepared from 5 g of polygalacturonic acid, 346.4 mg 45 C: 31,42 39.41 basic Mg-polygalacturo- containing magnesium H: 4.21 4.16 n suspension, with constant, intense stirring mg: 7.7 6.78 ben 6.2835 g adenosine 5'-triphosphoric acid disodium N 2.0 2.19 salt (C ₁₀ H ₁₄ N ₅ O ₃ P ₃ Na ₂ ). The reaction mixture was lyophilized. B: 0.661 0.845 dried by lysing 9.8 g of the title product 50 Vitamin B ₆ : 26.5 32.15 (B _ö -vitamin- we get. the hydrochloride The mixed complex calculated) HO- [Mg ²⁺ (C ₆ H ₇ O ₆ -) (OH ") o, 2 (C ₁₀ H ₁₃ N ₅ O ₁₃ P ₃ Na ₂ ) _0-18 ( _C 6 H _{10 O} 5) _{0 12] 4} ] _{N -} H Example 13 elemental analysis results for 55 Magnesium polygalacturonate-glycine mixed complex

(%) Calculated (%) C: 24.35 27.08

H: 3.77 2.91

N: 7.18 8.27

P:

mg:

found (% w / w) 8.7 3.5 calculated (w / w) 10.98

3.59

Example 11

Preparation of Magnesium Polygalacturonate-Pyridoxal-5-Phosphate Mixed Complex g of freshly prepared Mg-polygalacturonate basic magnesium containing 921.3 mg in aqueous medium was reacted with 8.0355 g of pyridoxal-5-phosphate (vitamin B; C ₈ H _{1 2} NO ₇ P). with vigorous stirring. The reaction mixture was dried by lyophilization to give 17.25 g of the title compound.

The mixed complex HO- [Mg ²⁺ (C 6 H ₆ O ₇ -) (OH) o, 2 (CgH] N0 ₇ P) O8 (C ₆ H ₅ 0 _io -) o.2i _4] n- Elemental analysis results for H:

found (% by weight) calculated (% by weight) C: 33.5 36.6 H: 4.97 4.04 N 2.51 2.5 P: 5.46 5.53 mg: 5.29 5.41 Expansion: 45.0 47.8

Example 12

Preparation of a mixed complex of magnesium polygalacturonate bis (pyridoxine hydrochloride borate)

Freshly prepared 1385.45 mg of magnesium basic magnesium polygalacturonate in an aqueous medium containing bis (6580.48 mg) of vitamin B ₆ (pyridoxine hydrochloride; C ₈ Hi, NO ₃ · HCl) and 989.28 mg of boric acid (H ₃ BO ₃ ) pyridoxine hydrochloride borate) with a complex acid under vigorous stirring. The resulting slurry was dried by lyophilization to give 23.89 g of the title product.

The mixed complex HO- [Mg ²⁺ (C ₆ H ₆ O ₇ ") (OH ^_) O] 6 ₍₂ Cl6H o0 N ₂ B _{7" 0 28} (CI ~) o) 5O] '• _(C6 Elemental analysis for H ₁₀ 0 ₅ ) o, ₂₁₄ ] nH:

Freshly prepared basic Mg-polygalacturonate from g (4.75 mol / kg acid equivalents) and 765.9 mg magnesium oxide in aqueous medium was reacted with 998.4 mg glycine (C ₂ H ₅ NO ₂ )

EN 213 872 Β while stirring. The reaction mixture was dried by lyophilization to give 5.5 g of the title compound.

Elemental analysis of the compound complex HO- [Mg ²⁺ (C ₆ H ₇ O ₆ ') (OH-) ₀ , 3 (C ₂ H ₄ NO 2 J _{0 7} (C ₆ H ₁₀ ClO 2, 214]) n-H:

C: found (% w / w) 34.2 calculated (% by weight) 39.41 H: 4.81 4.21 N 3.5 3.37 mg: 8.23 8.35 glycine: 17.9 17.83

Example 15

a) Preparation of a mixed complex of magnesium polygalacturonate-acetylsalicylate from g of polygalacturonic acid and 0.766 g of freshly prepared basic Mg-polygalacturonate in water with vigorous stirring and stirring with 3.08 g of acetylsalicylic acid (7.5 g). g of the expected product are obtained.

I θ Results of elemental analysis of the compound complex HO - [Mg ²⁺ (C ₆ H ₇ O ₆ “) (OH“) oj (C j HiCU'o /) © 6Ηιο0 ₅ ^- ) ο _ί 214] ν'Ή:

Example 14 15

Preparation of mixed magnesium polygalacturonate salicylate complex g (4.2 mol / kg acid equivalent) of pectin, 677.21 mg (16.8 mmol) of magnesium oxide and 1160.21 mg (8.4 mmol) of salicylic acid (C ₇ H ₆ O) ₃ ) Using starting materials 20, each of the three process variants is prepared in a Mg polygalacturonate-salicylate mixed complex.

Process variant (a): first, the pectin is reacted with magnesium oxide and then the basic 25 Mg polygalacturonate thus formed with salicylic acid.

b) Life-variant: first, the salicylic acid is reacted with magnesium oxide and then the resulting reaction product with pectin.

Process variant (c): The aqueous mixture of pectin and salicylic acid is reacted with magnesium oxide.

The reaction mixture was dried by lyophilization to give 6.4 g of the title compound for each variant.

The mixed complex 35

HO- [Mg ²⁺ (C ₆ H ₆ O ₇ ") (OH) 0 5 (CyHsOj'üí (C6Hio06 ^_) p 353] The results of elemental analysis for the N-H chemical formula:

found (% by weight) calculated (% by weight) 40 C: 39.6 41.78 H: 4.85 4.056 mg: 7.1 7.28

The identity of the product of the three live versions is confirmed by their infrared spectrum. Table 1 contains the antisymmetric and symmetric vibration bands [v _as (COO) and v _s (COO) of the carboxylate groups of the mixed complexes, expressed in cm ¹ :

Table 1

IR band Alternate method the) b) c) v _as (COO ^- ) 1605.7 1605.7 1604.6 1628.3 1629.2 1629.6 v _s (COO-) 1396.3 1396.1 1397.3

found (% by weight) calculated (ie C: 42.8 46.53 H: 4.2 3.92 mg: 5.93 6.12 acetylsalicylic acid: 38.4 40.67

b) Preparation of mixed magnesium oligogalacturonate acetylsalicylate complex

A fresh suspension of 200 mg of oligogalacturonic acid (octamer, N = 8, Institute of Chemistry of the Slovak Academy of Sciences, Bratislava) and 45.2 g of magnesium oxide freshly prepared as an aqueous suspension is stirred with 181.8 mg of acetylsalicylic acid under vigorous stirring. The reaction mixture was dried by lyophilization to give 439 mg of the title compound.

Results of elemental analysis for HO- [Mg ²⁺ (C ₆ H ₇ O ₆ -) (OH-) _{0> 1} (C ₉ H ₇ 0 ₄ -'O, 9] n-H (N '<8) in the mixed complex :

found (% by weight) calculated (% by weight) C: 43.1 46.4 H: 3.9 3.74 mg: 6.56 6.67 acetylsalicylic acid: 42.7 44.22

Example 16

Preparation of a mixed complex of magnesium polygalacturonate (- 5,5-diethyl) barbiturate from g of pectin (4.2 mol / kg equivalents) and freshly prepared basic Mg polygalacturonate from 338.6 mg (8.4 mmol) of magnesium oxide of 5,5-diethyl-barbituric acid (C8H10O3Ni) (mg, 0.84 mmol). The reaction mixture was dried by lyophilization to give 2.682 g of the title compound.

The results of elemental analysis for the N-H chemical formula - the mixed complex HO- [p i (C6Hio06 ^_) O, 214 mg of ² '(C ₆ H ₇ O ₆₎ (OH') p _{J9 (C8} Hti0 ₃ N _2)]:

found (% w / w) 32.8 5.1 calculated (w / w) 36.37 4.316

HU 213,872 Β

found (% by weight) calculated (% by weight) found (% by weight) calculated (% by weight) N, 1.09 0.966 C: 49.2 51.71 PMg: 7.85 8.38 H: 6.3 5.92 mg: 5.85 6.01 Example 17 Ejozapentaenoic acid: 15.9 16.55 Magnesium polygalacturonate-acid coffee docosahexaenoic acid: 16.3 17.98

preparation of a mixed complex

Example 20 An aqueous suspension of 162.5 mg (4.75 mol / kg acid equivalent) of freshly prepared basic polygalacturonate of polygalacturonic acid and 28 mg of magnesium oxide was reacted with 100 mg of coffee acid (C ₉ H ₈ O ₄ ) with vigorous stirring. The reaction mixture was dried by lyophilization to give 0.27 g of the title compound.

The mixed complex

HO- [Mg ^2- (C ₆ H ₇ O ₆ -) i, _u (OH) o, 09 (C ₉ H ₇ O ₄ -) o, 8 '(C ₆ H] c 10 05) o 23 ₇ ] n ^ Elemental analysis results for H:

found (% by weight) calculated (% by weight) C: 43.2 45.65 H: 4.1 3.94 mg: 5.92 6.05

coffee acid: 33.2 35.65

Example 18

Preparation of a mixed complex of magnesium polygalacturonate quercetin

An aqueous suspension of freshly prepared basic Mg-polygalacturonate (162.5 mg, 4.75 mol / kg acid equivalent) in polygalacturonic acid and 28 mg of magnesium oxide was reacted with 158.5 mg of quercetin (C 15 H ₁₀ O ₇ ) with vigorous stirring. The reaction mixture was dried by lyophilization to give 0.33 g of the title compound.

The mixed complex HO- [Mg ²⁺ (C ₆ H ₆ O ₇ -) i _j m (OH ^-) p, 133 (Cl ₅ H ₉ O ₇ -5o, 756 '(COH] ^_ Οθ5) θ, 237] Ν Results of elemental analysis of '-H':

found (% by weight) calculated (% by weight) C: 45.4 47.87 H: 3.9 3.51 mg: 4.8 4.99 quercetin: 43.9 46.73

Example 19

Preparation of a mixed complex of magnesium polygalacturonate and eicosapentaenoic acid-docosahexaenoic acid

Basic aqueous suspension of Mg polygalacturonate freshly prepared polygalacturonic acid 162.5 mg (4.75 mol / kg acid equivalent number) and 28 mg of magnesium oxide with vigorous stirring 97.2 mg of eicosapentaenoic (C ₂ oH3o0 ₂₎ and docosahexaenoic acid (C ₂₂ H ₃₂ O ₂ ) with a 1: 1 molar mixture. The reaction mixture was dried by lyophilization to give 0.26 g of the title compound.

The mixed complex HO-TMG ^ Ce ^ Odun (OH ") o _I44 5 (C ₂ oH ₂₉ 0 _{2) 0,} 222 (C 22 H ₃ i0 ₂ ^-) p _j2 22 (C ₆ H i Οθ5) θ, 237] Ν ' Elemental analysis results for _H:

Zinc polygalacturonate-pyridoxal-5-phosphate solution of a mixed complex of basic zinc polygalacturonate freshly prepared (4.75 mol / kg acid equivalent number) polygalacturonic acid g and 2.329 g of zinc dust in aqueous suspension with vigorous stirring 4.725 g of pyridoxal-5-phosphate (B _é -vitamin15 phosphate ; C ₈ H ₁₂ NO ₇ P) in distilled aqueous solution. The reaction mixture was dried by lyophilization to give 14.2 g of the title compound.

The _{mixed complex has} HO- [Zn ²⁺ (C ₆ H ₇ O ₆ -), _{j 333} (OH ~) o 166 (C ₈ Hn NO ₇ P-) ₀ , 501 (C (, H 10 O ₅ ) o _: 2 ₈ 3). Elemental analysis for n ^ H:

found (% by weight) calculated (% by weight) C: 31.38 34.29 H, 4.14 3.72 N, 1.0 1.46 P: 3.01 3.23 Zn: 13.1 13.63 Bé vitamin phosphate: 23.5 27.57

Example 21

Preparation of a mixed complex of ferric polygalacturonate ascorbate folate

A freshly prepared aqueous suspension of basic iron (II / III) polygalacturonate (containing 4,422 g of iron) was first reacted with 393 mg of folic acid (vitamin Bg; ClgHlgN706) under vigorous stirring and then 4.03 g of L-ascorbic acid was added. The resulting mixed complex40 was dried by lyophilization to give 31.3 g of the title compound.

The mixed complex

HO- [Fe ²¹⁺ (C ₆ H ₇ O ₆ ^- ) i, 2 (ΟΗ ^- ) 0, ₆ (C ₆ H ₇ 0 ₄ -) o, ₂₈ s.

Elemental analysis for T ascorbate • (C1 ₉ H _{18 8} N ₇ 0 ₆ -) o, 12 (C ₆ H 1 Οθ 5) θ, 255]:

C: found (% w / w) 29.34 calculated (% by weight) 34.36 H: 4.27 3.69 N 1.0 0.31 Fe: 15.78 14.96 Vitamin C: 12.95 13.52 folic acid: 1.2 1.37

Example 22

Preparation of Iron (II / III) Polygalacturonate-Riboflavin-5'-PhosphateNa Mixed Complex

Freshly prepared basic (containing 787 mg iron)

An aqueous suspension of iron (II / III) polygalacturonate of iron (II / III) is reacted with 2174 mg of riboflavin-5'-phosphate-Na dihydrate (vitamin B ₂ ; C ₁₇ H ₂ O ₄ N ₄ O ₉ P-2H ₂ O) with vigorous stirring. . The resulting mixed complex suspension was dried by lyophilization to give 6.91 g of the title compound.

The mixed complex

HO- [Fe ² ' ⁷⁺ (C ₆ H ₇ O ₆ ) 12 (OH ^- ),, 2 (C ₁₇ H ₁₉ N ₄ NaO ₉ p-) o, ₃ . • Elemental analysis for (C6H, ₀ 0 ₅ ) o ₂₅₅ ] n ^ H:

C: Found (% w / w) 32.27 calculated (% by weight) 35.25 H: 4.46 3.79 N 3.52 3.57 P: 2.02 1.97 Fe: 11.38 11.86 So: 1.5 1.46 Vitamin B ₂ : 29.24 30.38

Example 23

Preparation of Manganese (II) Polygalacturonate Thiamine Pyrophosphate Mixed Complex

Alkaline manganese (II), freshly prepared (containing 439.5 mg of manganese) -poligalakturonát aqueous suspension of 1894 mg of thiamine pyrophosphate (Β, vitamin Cl ₂ H ₈ N ₄ O ₇ P ₂ S-4H ₂ O) with intensive while stirring. The reaction mixture was dried by lyophilization to give 2.6 g of the title compound.

The mixed complex HO- [Mn ²⁺ (C ₆ H ₇ O ₆ ), ₂ (OH-) o _{> 3} (C, ₂ H, ₇ N ₄ 0 ₇ P ₂ S)], 5 '(C ₆ H ₁₀ O ₅ ). o, 256] The results of elemental analysis of n '"H are:

found (% by weight) calculated (% by weight) C: 33.15 33.80 H: 5.03 3.78 N 5.42 5.35 P: 6.13 5.92 S: 2, g7 3.06 Mn: 10.42 10.51 B Vitamin 38.1 40.4 Example 24

Preparation of Manganese (II) Polygalacturonate Pantothenate Mix Complex

An aqueous suspension of freshly prepared basic manganese (II) polygalacturonate from 29.45 g (4.75 mol / kg acid equivalent) of polygalacturonic acid was reacted with pantothenic acid (C ₉ H, ₇ NO 5) (10 g Ca-pantothenate liberated) under vigorous stirring. The reaction mixture was dried by lyophilization to give 45.9 g of the title compound.

The mixed complex HO- [Mn + ² (C6H7O6 -) ,, 333 ^(_ OH) p, 267 (C ₉ H ₁₆ N0 ₅ -) p, • ₄ (C 6 H, ₀ 05-) p ₂ 8 _3] n ' Results of elemental analysis of H-formula:

found (% by weight) calculated (% by weight)

C: 34.52 37.46

found (% by weight) calculated (% by weight) H, 5.13 4.41 N, 1.0 1.32 Mn: 12.56 12.9 Pantothenic acid: 19.8 20.5 Example 25

Preparation of Manganese (II) Polygalacturonate Ascorbate Menadione Sulphite Complex

Basic Mn (II) polygalacturonate containing 265.47 mg of manganese with 130.65 mg of L-ascorbic acid followed by 2004 mg of menadione sodium bisulfite (vitamin K ₃ ; C 1, H ₉ O ₂ SO ₃ Na) (hydrogen Reaction with an ion exchanged solution of Varion KS resin type C, manufactured by NITROCHEMISTRY, willow in an aqueous medium with vigorous stirring. The resulting mixed complex suspension was dried by lyophilization to give 21.1 g of the title product.

The mixed complex

HO— [Mn ²⁺ (C ₆ H ₇ O ₆ -) ,, ₃₃ (OH-) ₀ , ₃₉ (C ₆ H ₇ O ₆ -) ₀ , ₁₅ 't ascorbate • (CiiHgO ₂ SO ₃ -) o, Elemental analysis of the formula for ₃ '(C6H, o05) o, ₄₇₇ ]> rH:

found (% by weight) calculated (% by weight) C: 32.48 36.7 H: 4.23 3.87 S: 1.0 0.98 Mn: 11.49 12.7

Example 26

Preparation of a mixed complex of copper (II) polygalacturonate mcotinate

A freshly prepared aqueous suspension of copper (II) polygalacturonate, containing 969.6 mg of copper, was reacted with 757.7 mg of nicotinic acid (vitamin B ₃ ; C ₆ H ₅ NO ₂ ) under vigorous stirring. The reaction mixture was dried by lyophilization to give 5.4 g of the title compound.

The compound complex has the formula HO- [Cu ²⁺ (C ₆ H ₇ O ₆ -), ₃₃₅ (OH) o, ₃ 18 (C ₆ H ₄ NO ₂ ") o, 347 (C ₆ H ₁₀ O ₅ ) o, ₂ 85] n'-H. results of relevant elemental analysis:

found (% by weight) calculated (% by weight) C: 33.43 36.2 H, 4.54 3.55 N, 1.0 1.24 Cu: 15.9 16.24 Vitamin B ₃ : 10.5 10.82 Example 27

Preparation of needle mixed complex magnesium polygalacturonate-catan-grass extract

A g of air-dried ground cabbage disease (Cichorium intybus) is extracted with 250 cm <^{3> of} 96% hot ethanol and filtered. The filtered extract was made up to 96 cm ³ with ethanol (96% by volume). The extract has a dry matter content of 1.61 g / 100 cm ³ , equivalent to acid12

EN 213 872 Β number 5.26 μιηοΐ / cm ³ , routine content 14.2 mg / 100 cm ³ , quercetin content 11.5 mg / 100 cm ³ . A 50 cm ³ portion of the above extract was reacted with a freshly prepared aqueous suspension of Mg polygalacturonate, 78.5 mg, at room temperature. The reaction mixture was dried by lyophilization to give 1.826 g of the title compound.

The _{compound of the mixed complex is} : HO- [Mg ²⁺ (C ₆ H ₇ O ₆ J (OH-) _0j92 (X ₁ -) ₀ , 08 (C

Example 28

Preparation of a mixed complex of magnesium polygalacturonate cathagan root extract 20 g of dried ground cuneiform root (Cichorii radix) were prepared as described in Example 27. The extract has a solids content of 416 mg / 100 cm ^3, acid equivalents of 3.68 pmol / cm ³ , routine content of 41 mg / 100 cm ³ , and quercetin content of 29 mg / 100 cm ³ .

A 50 cm ³ portion of the above extract was reacted with basic magnesium polygalacturonate (77.49 mg) in an aqueous medium under vigorous stirring. The reaction mixture was dried by lyophilization to give 1.196 g of the title compound.

The compound formula has the following general formula: HO- [Mg ²⁺ (C ₆ H ₇ 0 ₆ -) (OH-) o _{; 94} (X 1) o, o ₆ (C ₆ H ₁₀ O ₆ ) t] n = H

Example 29

Preparation of Mixed Magnesium Polygalacturonate Dandelion Extract Compound Following the procedure of Example 27, 25 g of dried ground dandelion extract (Agrimonia eupatoria, herba) were prepared. The extract had a dry matter content of 1.838 g / 100 cm ³ , an acid equivalence of 37.72 pmol / 100 cm ³ , a routine content of 120.5 mg / 100 cm ³ and a quercetin content of 297 mg / 100 cm ³ .

A volume of 25 cm ^{3 of} the above extract was reacted with 1.5 g of freshly prepared basic magnesium polygalacturonate containing 7.72% magnesium in aqueous medium with vigorous stirring. The reaction mixture was dried by lyophilization to give 1.902 g of the title product.

The compound of the mixed complex is: HO- [Mg ²⁺ (C ₆ H ₇ 0 ₆ -) (OH-) o ₁₈ (X ₁ -) o, ₂ (C 0 H 1 Οθ 5) θ, 61] n-H

Example 30

Preparation of a mixed complex of magnesium polygalacturonate-straw-couple extract Using the procedure of Example 27, 10 g of dried-powdered straw-couple (Helichrysum arenarium) were prepared. The extract contained a solids content of 796 mg / 100 cm ³ , an acid equivalence number of 16.31 pmol / cm ³ , a routine content of 186 mg / 100 cm ³ , and a quercetin content of 93.8 mg / 100 cm ³ .

40 cm ³ portion of this extract is reacted with 1.5478 g of basic magnesium poligalakturonáttal containing 7.72% by weight magnesium in an aqueous medium with vigorous stirring. The resulting mixed complex suspension was dried by lyophilization to give 1.8 g of the title compound.

The compound formula of the mixed complex:

HO- [Mg ²⁺ (C ₆ H ₇ O ₆ -) (OH-) o, 867 (XDo.m (C ₆ H ₈ O ₀ θ 5) ο, 61] n = H.

Example 31

Preparation of Magnesium Polygalacturonate Dandelion Extract Mixed Complex Following the procedure of Example 27, 10 g of dried powdered dandelion root extract (Taraxacum officinala, radix) were prepared. Extract solids content: 655 mg / 100 cm ³ , acid equivalents:

16.83 pmol / cm ³ , routine content: 19.9 mg / 100 cm ³ , quercetin content: 11.6 mg / 100 cm ³ .

A 50 cm ³ portion of the above-mentioned chain extract extract was reacted with 1 g of freshly prepared basic magnesium polygalacturonate containing 7.72% magnesium in aqueous medium with vigorous stirring. The reaction mixture was dried by lyophilization to give 1.28 g of the title compound.

The mixed compound has the following general formula: HO- [Mg ²⁺ (C ₆ H ₇ O ₆ -) (OH-) 0, ₇ 36 (Xf) 0, 264 (C ₆ H ₁₀ O ₅ O ₂ O ₁ H ₁ -H.

Example 32

Preparation of a mixed magnesium polygalacturonate-stonewort extract of anthrax extract (g) (4.2 mol / kg acid equivalent) of an aqueous colloidal solution of pectin (281.9 mg lyophilized, 1.49 mmol / g acid milled rock rose) (8.4 μιηοΐ) of magnesium oxide was added under constant stirring. After completion of this stage of the reaction, while stirring continued, 142.4 mg (2.95 μιηοΐ / g acid equivalent) of milk thistle (Slybum marianum) were known [H. Wagner et al., Arzneimittel-Forschung (Drug Res.) 18: 688-696 (1968)] is added to the reaction mixture. After completion of the reaction, the mixed complex suspension was dried by lyophilization to give 2.916 g of the title product.

Mixed complexes have the formula: HO- [Mg ²⁺ (C ₆ H ₆ O ₇ -) (ΟΗ-) ο, ο ₉ (Χγ), 05 (Xf), 0.05 (C6 H | ₀ 0 _5), p 35] n = FI (In the above formula, X represents the anion derived from the acidic components of the rock rose while Xj represents the anions derived from the acidic components of the milk thistle.)

Example 33

Mixed complex magnesium-polygalacturonate-nyárfarügy extract solution of g, basic poligalakturonátot freshly prepared containing%, 7.33 by weight of magnesium in an aqueous medium 86.22 cm ³ alcohol is reacted with 2.798 mmol / 100 cm ³ acid equivalents of SEQ extract obtained nyárfarügyből (Populus nigra, gemma) Intensive while stirring.

The poplar bud extract is prepared as follows: 50 g of ground dry poplar bud are mixed with 200 cm ^{3 of} distilled water for 24 hours at 35 ° C and then

Filter and dry the solid filtrate. The resulting dry drug was extracted with petroleum ether for 5 hours in a Soxlet extractor, re-dried and then extracted with 200 cm ^{3 of} 65% ethanol for 3 hours. The resulting extract was made up to 65 cm ³ with ethanol (65% by volume).

The reaction mixture was dried by lyophilization to give 5.02 g of the title compound.

The compound formula has the following general formula: HO- [Mg ²⁺ (C ₆ H ₇ O ₆ -) (OH-) o, 6 (Xr) o, 4 (C ₆ H ₁₀ O ₅ ) o, 5i] n'-H

Example 34

Preparation of Ferrocomp tablet

Using process variant (a), a mixed polygalacturonate-folate complex is prepared and the product is isolated by spray drying. The resulting Ferrocomp powder contains 133 mg of the following components: 5 mg iron, 1.5 mg zinc, 0.5 mg manganese, 0.5 mg copper, 0.03 mg cobalt, 13 mg potassium and 0.1 mg mg folic acid (C ₁₉ H, ₉ N ₇ O ₆ ). 280 and 420 mg of L-ascorbic acid are added as standard antioxidant excipients to 133 mg and 266 mg of this active ingredient, with the addition of standard tableting excipients such as magnesium stearate, alkali, polyvinyl butyral and 20-40 mg of L-ascorbic acid per tablet. and then coating the tablets by standard techniques. Ferrocomp tablets can be used to prevent and cure anemia (1-3 x 2 tablets daily). The formula of the active compound complex:

HO _ {[Me ^{z +} (C6H7O6 ^_) (OH ') (C ₁₉ H ₁₈ N ₇ O ₆ -) _m [R ⁺ (C ₆ H ₇ O _{6')] x} (C ₆ H ₁₀ O _{5) y}} P _N -H where z is 2.8329601 a is 1.8312167 m is 0.00174336 x is 2.5714285 y is 1.2293303

Published by: 0.6889696 Fe ³⁺ + 0.1765263 Zn ²⁺ + +0.0605496 Cu ²⁺ + 0.0700369 Mn ⁴⁺ + 0.0039173 Co ³⁺ .

Example 35

Preparation of wheat flour enriched with mixed complex of magnesium polygalacturonate-rock-lime-thyme extract

3 g of the mixed powder of the dried, dried and finely ground compound prepared according to Example 32 is homogenized with 6 kg of wheat flour. The flour of increased biological value thus produced contains 0.05% by weight of a mixed complex.

Table 2

The wavelengths of the antisymmetric [iron (COO) vibration bands of the carboxylate groups in cm &^lt; -1 &^gt;

Example Number of waves (cm ') Example Number of waves (cm ') First 1628 18th 1611 Second 1620 19th 1626 Third 1635 20th 1615 4th 1630 21st 1610 5th 1635 22nd 1622 6th 1620 23rd 1610 7th 1600 24th 1619 8th 1608 25th 1618 9th 1625 26th 1630 10th 1645 27th 1626 11th 1629 28th 1627 12th 1620 29th 1625 13th 1634 30th 1625 15a) 1610 31st 1627 15 b) 1605 32nd 1630 16th 1628 33rd 1626 17th 1638 34th 1612

Claims (4)

PATENT CLAIMS 1. Mixed complexes of oligo- or polygalacturonate of formula (I) HO - [{Me ^{z +} (Ps-U, (OH-) _a (HCO ₃ ) _b (CO?) _C (X ^) _m } (M ⁺ Ps ~) _x G _y ] _N -H (I) Me represents an alkaline earth metal atom and / or a transition metal atom, Ps means galacturonate ion, XA is independently an anion of an inorganic and / or organic acid having therapeutic and / or beneficial physiological activity, where nj is the charge number of anion Xj, which is an integer from 1 to 10, M is an alkali metal, G is the neutral saccharide unit free of the carboxylate group, z is the (average) charge number of Me atoms in the mixed complex molecule having a real number between 2 and 3, q is the stoichiometric coefficient of a, b, c and m ⁿ i ^m , expression, with ai = l EN 213 872 Β with the proviso that its value is a real number ranging from 0.0001 to (z-1), 1000 where X name is the sum of the charge of the anions X, 'in the compound complex molecule ^{1 = 1} , a, b, and c are each independently a real number greater than 0 or 0, provided that + b + 2c is at most z Can be -1,0001, m is a real number from 0.0001 to 2, x is a real number from 0 to 56, y is a real number from 0 to 35, and N 'is the average degree of polymerisation (N) of 2 <N <300. (Priority: 07/07/1994) Pharmaceutical compositions, characterized in that the active ingredient is a compound of the formula I in which Me, Ps -, X ₍ ¹ , M, G, z, q and N ') and a, b, c, n ,, m, x and y are as defined in claim 1 - and include conventional pharmaceutical carriers, diluents, and / or other excipients (Priority 01/07/1994). 3. A food composition, characterized in that one or more of the compound complexes of formula (I), wherein Me, Ps', X _; , M, G, z, q and N 'and a, b, c, n, m, x and y are as defined in claim 1 - and commonly used food ingredients. Priority: 07/07/1994) 4. A method vegyeskomplexek formula I according to claim 1 (I) in the preparation of - wherein Me, Ps ^_ x ^{i, 1} M, G, Z, Q, and N 'is and a, b, c, _η ί ₍ 15, x and y are as defined in claim 1, characterized in that a) a basic metal oligo or metal polygalacturonate of formula II H0 - [{Me ^{z +} (Ps ^- ) ₂ _ _q · - in which formula Me, Ps', M, G, z, and N ', and a, b, c, x and y are as defined in claim 1, q' is a + b + 2c formed from stoichiometric coefficients a, b and c with the proviso that a value of 0.001 to (zl) real number (H ⁺ ) is reacted with an acid or acids of the formula "A ^1" wherein X ¹ is and n is as defined in claim 1, or b) the acid (s) of formula (H ⁺ ) nx, ¹ , wherein Xt ¹ is and η is the above Me metal (s) or Me compound (s), where Me is as defined above, and ( OH ^- ) a (HCO3 -) b (CO3 ^2- ) c} (MW) _x G _y ] _N - -Η (Π) the oxide (s), hydroxide (s) of the compound (s), ka) t, hydrogen carbonate (s) or basic carbonate (s), and the resulting compound (s) is reacted with oligo- or polygalacturonic acid or pectin, or C) reacting a mixture of oligo- or polygalacturonic acid or pectin and ( ^{H +} ) n, ^x i ⁿ 'acid (s) with a metal (s) Me or a compound (s) thereof and optionally obtaining the resulting compound (I); H ⁺ ) ". X + ·, a), b) Used other than 35 or c) embodiments, acid (s) from an acid, wherein x i is ¹ and nj are as defined above - is reacted.