DE102021115047A1 - Carboxylic acid loaded salt carrier and the process for the preparation thereof - Google Patents

Abstract

The present invention provides a carboxylic acid-loaded carboxylic acid salt carrier as a free-flowing powder that is a particulate solid. The compound of the invention is stable, biocompatible, and digestible, allows high acid loading and controlled release of adjustable acid strength in solution, and facilitates liquid handling Carboxylic acids such as formic acid, acetic acid, glycolic acid, propionic acid, butyric acid and lactic acid in powder form. The compound of the invention is soluble in polar solvents, except for the carrier component which is thermally stable up to 300°C. The present invention further provides a process for the preparation of the flowable compound of the invention which comprises loading a carrier carboxylic acid with at least one loaded carboxylic acid ( n), selected from the group of preferably liquid short-chain carboxylic acid(s), by contacting the components of an alkaline earth metal base, carrier carboxylic acid and the charged carboxylic acid(s). The pulverulent product obtained by the process according to the invention has low moisture content, a defined and homogeneous particle size, free-flowing and non-caking properties.

Description

Technical field of the invention

The present invention relates to an organic acid-loaded solid compound, particularly a carboxylic acid-loaded carboxylic acid salt carrier having free-flowing, homogeneous, particulate properties exhibiting controlled acid release, and discloses the manufacturing process therefor.

State of the Art / Background

Organic acids are used in a variety of applications due to their organoleptic, physiological, and chemical properties. Organic acids are carbonaceous chemical compounds comprising molecules or ions with a functional group capable of donating a proton, also known as the hydrogen ion H ⁺ , in an equilibrium reaction with bases or proton acceptors such as water. In the case of water as a proton acceptor, the oxonium ion H ₃ O ⁺ is formed, which makes a solution acidic. Acidity is a key factor in a variety of applications such as buffering of (bio)chemical assays, preservation, cosmetic formulations, antimicrobial formulations, as an excipient in pharmaceutical applications and is thus an essential factor in many manufacturing industries. The propensity to donate a proton is measured by the acidity constant (or pK _a value) of a substance, which indicates the acid strength of a molecule. This means that acid strength increases with decreasing pK _a value. Constituents that are able to donate more than one proton are described by several pK _ax , with each pK _ax describing the acid-base reaction of the xth proton.

Most organic acids donate a proton through their carboxyl group (-COOH) and in this case are called carboxylic acids. As basic chemicals for technical compounds in food, personal care products, plastics, surfactants and detergents, complexing agents, dyes and numerous other consumer and industrial goods, carboxylic acids are of great economic importance for global large-scale production. In times of globalized production, efficient management of basic chemicals such as organic acids is a prerequisite for downstream processes of global development, and economical, safe and uncomplicated transport of effective, inexpensive and easily dosed organic acid compounds is of fundamental importance for modern industry.

In the pharmaceutical, cosmetic, food and feed industries, short-chain carboxylic acids with a carbon chain length of less than five carbon atoms are used as acidulants, flavoring agents, pH buffers and microbial growth control agents, while liquid carboxylic acids such as acetic acid are used in a number of pharmaceutical applications how kidney dialysate is used. Short chain liquid carboxylic acids used in these areas are typically formic, acetic, glycolic, propionic, lactic and butyric acids. These substances are beneficial and generally non-harmful at low concentrations in the final products, typically 2 to 10% by weight or less, as reported by Stratford (2003), Kornhauser et al. (2010) and documented in numerous scientific articles. However, these substances are corrosive, flammable, volatile and classified as dangerous goods in their concentrated form. Therefore, these substances are subject to the European Commission's dangerous goods regulations (2008), which makes their transport and storage expensive, as also shown by Rytkönen (2006). These acids are therefore hardly safe to handle in the pharmaceutical, cosmetic, food or animal feed industries and can pose a hazard to the environment, among other things.

In order to reduce the high transport costs or to reduce the hazardous properties, these liquid short-chain carboxylic acids are often (partially) neutralized and/or diluted. The lower concentration of active ingredient when diluting/neutralizing such liquid acids results in reduced application efficacy, e.g. in relation to their antimicrobial and acidifying properties.

A specific example of such use in the food industry is in the patent US20080317921A1 by controlling Listeria monocytogenes, E. coli and other pathogens in meat products using an aqueous sodium lactate solution mixed with vinegar, acetic acid, or an acid salt thereof. Attempting to compensate for the dilution of organic acids by using a higher amount of the diluted compound results in limited effectiveness and high transport costs, which makes the use of short-chain carboxylic acids in the various industries impractical and uneconomical. In addition, diluted forms of acids are usually also subject to the provisions of the dangerous goods transport law. Similar handling challenges are observed for formic, acetic, propionic, lactic, glycolic and butyric acids, which are used as buffers, fragrances, humectants, antimicrobials, preservatives, pH adjusters and skin conditioning agents in both cosmetic and dermatological applications applications (see cosmetic ingredients database CosING), making these challenges a major constraint for a broad industrial field. Similarly, other organic acids such as salicylic acid or benzoic acid are also used in the cosmetic and pharmaceutical industries for their antifungal and preservative function, with salicylic acid being used for its keratolytic properties.

These substances exhibit similar problems when handling acids, making the manufacturing processes less efficient and therefore more expensive.

A common approach to improve the handling of carboxylic acids is the adsorption of the aforementioned acids in high surface area mineral carrier systems. WO 9707687 discloses a granulate consisting of a core material made of a porous support, an organic acid and a swellable coating material. Similar near-surface mineral carrier systems consist of mineral silicates such as precipitated silicic acid, zeolites, bentonite, vermiculite or kieselguhr. The mixing of carboxylic acids and mineral silicates gives solid products with a carboxylic acid content of typically 30 to 70% by weight. Such products are currently used in the feed industry as so-called "acidifiers" to promote animal growth and health, as in EP1761133B1 described wherein the carrier is diatomaceous earth. However, this approach is suboptimal due to the high proportion of non-functional, inert and indigestible silicate carriers. Mineral silicates such as magnesium aluminum silicate are used as absorbents in the cosmetics industry, but their potential as acid carriers has not yet been exploited.

2002/0086090 discloses a solid preparation of mixed acids made from sorbic acid, at least one liquid organic acid and at least one other solid organic acid, each based on the physical state at room temperature (23° C.). The compound is a pure acid mixture, i.e. there is no chemical reaction between the acids, no carrier is formed and therefore a cost-effective transport of the acids is not possible due to the dangerous goods regulations.

Another possible industrial application of carboxylic acids is the use of acid adducts of the alkali metal salts of carboxylic acids, for example sodium or potassium diacetate. These substances are solids with the following structure M ⁺ RCOO ^- · RCOOH

M ⁺ is a sodium ion (Na ⁺ ) or potassium ion (K ⁺ ), RCOO ^- is a short chain carboxylate ion such as acetate and RCOOH is the corresponding short chain carboxylic acid such as acetic acid. The resulting solid acid acetate salt can be used, for example, to impart a salty and vinegary flavor to potato chips or salad dressings, as in US3672914A described. However, according to the CosING database, adducts such as potassium or sodium diacetate have limited registration for cosmetic products in the EU and are not relevant to the technical challenges of a broader industry. Alkali metal cations, practically limited to sodium or potassium, are associated with characteristic modern lifestyle diseases such as obesity, coronary artery disease, type 2 diabetes or hypertension, as reported by Grillo et al. (1970), while excess potassium has a laxative effect on the human and animal digestive tract and may contribute to hyperkalemia, as demonstrated by Mandal (1997). In addition, the fixed stoichiometric ratio between the monovalent alkali metal cation salt and the short chain carboxylic acid is disadvantageous. In this context, it is highly desirable to provide the benefits of organic acids, particularly short chain carboxylic acids, in an inclusion of alternative bioavailable metal salts that preferably support human and animal health as essential agents in biochemical processes, since magnesium is e.g. important for muscle contraction, blood clotting or vitamin absorption and calcium is an important building block of bones and teeth. To date, there are disadvantages in handling and transporting liquid carboxylic acids and the special dosage requirements lead to limited applicability due to the high cost of the compounds.

Object of the Invention / Technical Problem

There is an urgent need to overcome the disadvantages of the above-mentioned existing organic acid compounds and to provide a safely processable, free-flowing, powdered compound capable of supporting and releasing liquid carboxylic acids in a controlled manner without the use of mineral carriers and without the need to incorporate sodium or potassium ions into the compound, while being adaptable to the type and level of acid loaded.

In addition, a process for the preparation of the described salt carrier loaded with carboxylic acid(s) should be simple, offer a high loading capacity for the loaded acids, be based on cheap starting materials and do not require additives or catalysts, and thus an economical synthesis of im enable industrial scale.

solution of the task

According to the invention, this object is achieved by a short-chain carboxylic acid, particularly preferably a C ₁ -C ₄ -carboxylic acid, which is loaded onto a carboxylic acid salt carrier according to claim 1, and the process for its production. Further advantageous developments of the invention are specified in the dependent claims.

vorzugsweise hergestellt durch ein hierin beschriebenes einfaches Herstellungsverfahren, das die folgenden Bestandteile aufweist
ein Carboxylsäure-Trägersalz ${\text{M}}^{2+}{\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

wobei
M²⁺ ein Erdalkalimetallion, vorzugsweise Calcium (Ca), Magnesium (Mg), Barium (Ba) oder ein zweiwertiges Metallion, ausgewählt aus Eisen (Fe), Kupfer (Cu), Zink (Zn), Mangan (Mn), Zinn (Sn) oder einer Mischung davon, ist,
R¹ eine gegebenenfalls substituierte C₁-C₁₀-Alkylgruppe oder eine gegebenenfalls substituierte Arylgruppe ist, wobei die Substituenten unabhängig voneinander ausgewählt sind aus einer Carbonylgruppe (=O), die vorzugsweise eine Carbonylgruppe benachbart zu einer Hydroxygruppe unter Bildung einer Carbonsäuregruppe umfasst, einer Aminogruppe (NH₂), einer Hydroxygruppe (OH), einem Halogen, einer Cyanogruppe (CN) oder einer Mischung davon, und wobei m 0 bis 2 ist,
eine beladene Carbonsäure R²COOH,
wobei R² eine gegebenenfalls substituierte C₁-C₁₀-Alkylgruppe ist, wobei die Substituenten unabhängig voneinander ausgewählt sind aus einer Carbonylgruppe (=O), vorzugsweise umfassend eine Carbonylgruppe neben einer Hydroxygruppe unter Bildung einer Carbonsäuregruppe, einer Aminogruppe (NH₂), einer Hydroxygruppe (OH), einem Halogen oder einer Cyanogruppe (CN) oder einer Mischung davon,
wobei 1 < n ≤ 6;
wobei der pK_a1 der entsprechenden Carboxylsäure der Trägercarbonsäure ${\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

≤ pK_a1 der beladenen Carbonsäure(n) R²COOH,
wobei die beladene(n) Carbonsäure(n) R²COOH innerhalb der Struktur des Trägercarbonsäuresalzes ${\text{M}}^{2+}{\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

physisorbiert ist (sind).Thus, the present invention provides a solid compound, which is produced as a powder and has good flowability, comprising the following structure, $${\text{<figure-callout id="2" label="M" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0045.png" state="{{state}}">M</figure-callout>}}^{2+}{\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}\cdot {\text{<figure-callout id="2" label="No" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0045.png" state="{{state}}">No</figure-callout>}}^2\text{COOH}$$

preferably made by a simple manufacturing process described herein, having the following ingredients
a carboxylic acid carrier salt ${\text{M}}^{}$${}^{2+}{\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

whereby
M ²⁺ an alkaline earth metal ion, preferably calcium (Ca), magnesium (Mg), barium (Ba) or a divalent metal ion selected from iron (Fe), copper (Cu), zinc (Zn), manganese (Mn), tin ( Sn) or a mixture thereof, is,
R ¹ is an optionally substituted C ₁ -C ₁₀ alkyl group or an optionally substituted aryl group, wherein the substituents are independently selected from a carbonyl group (=O), preferably comprising a carbonyl group adjacent to a hydroxy group to form a carboxylic acid group, an amino group (NH ₂ ), a hydroxy group (OH), a halogen, a cyano group (CN) or a mixture thereof, and where m is 0 to 2,
a loaded carboxylic acid R ² COOH,
wherein R ² is an optionally substituted C ₁ -C ₁₀ alkyl group wherein the substituents are independently selected from a carbonyl group (=O), preferably comprising a carbonyl group adjacent to a hydroxy group to form a carboxylic acid group, an amino group (NH ₂ ), a Hydroxy group (OH), a halogen or a cyano group (CN) or a mixture thereof,
where 1 < n ≤ 6;
where the pK _a1 of the corresponding carboxylic acid of the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

≤ pK _a1 of the loaded carboxylic acid(s) R ² COOH,
wherein the loaded carboxylic acid(s) R ² COOH within the structure of the carrier carboxylic acid salt ${\text{M}}^{}$${}^{2+}{\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

is (are) physisorbed.

The invention relates to salt carriers loaded with carboxylic acid and their synthesis, which result in dry powdered carrier salts that have significant advantages in terms of dosability and processability, such as good flowability and high acid effectiveness due to high molar concentrations without restrictions due to dangerous goods regulations. These acidic, solid, and free-flowing compounds can be used in pharmaceutical, cosmetic, food, and feed applications.

A novel process for the production of short chain carboxylic acids, preferably C ₁ -C ₄ carboxylic acids, by physisorption thereof within a salt carrier as described herein and in the claims has been discovered. The process involves the reaction of a carrier acid and a source of alkaline earth metal ion, preferably as a base, with the loading acid(s) present in the reaction mixture and is performed synoptically by mixing the starting materials under thermal control followed by drying the sized powder from the condensate by-product. Taking advantage of the acid strength of the starting materials, this process produces a physisorbed acid inclusion component of a carboxylic acid-loaded salt carrier in good yields, providing an acid-functional powder with good flowability.

Advantageous Effects of the Invention

Benefits and description of the product

Inclusion / Physisorption

The compound of the invention relates to a series of carboxylic acid-loaded carboxylic acid salt carriers, short acid-loaded carriers which have controlled acidity and are in powder form and have short-chain liquid carboxylic acids. As used herein, the term powder refers to a particulate material that is in a solid or semi-solid state when placed in an open container at atmospheric pressure and room temperature (r.t., 23°C).

An inclusion compound, such as the carboxylic acid-loaded carboxylic acid salt carrier of this invention, is a compound in which one chemical moiety, the carrier, has the ability to encapsulate other moieties. The encapsulation of reactive moieties such as short chain carboxylic acids has significant advantages as the loaded moieties are physisorbed in the matrix/void of the support material, which is an interaction without covalent bonding, thereby mediating their reactivity in the encapsulation. The mediated reactivity of the support loaded with the reactant allows their acidity to be controlled, which is essential for the industrial exploitation of reaction sequences.

The mediated reactivity of an inclusion compound advantageously facilitates, inter alia, safety/stability during storage or during transport in technical chemistry.

The strength of the physisorption is an important indicator for the stability of the inclusion compound according to the invention and can be analyzed semi-quantitatively by means of thermal analysis. Thermal analysis is the analysis of the change in a property as a function of a given temperature change. Thermogravimetric Analysis (TGA) is the most widely used thermal analysis method and measures the change in weight in a material as a function of temperature (or time) and is therefore suitable for assessing the quality of the compound of the invention by being the most important for the stability of an inclusion formulation relevant physicochemical transformations, such as desorption processes, decomposition and/or dehydration, are analyzed. The compounds according to the invention advantageously show controlled desorption of the loaded acids, which can be induced independently of the likewise thermally induced purification of the compound according to the invention. Furthermore, it has been shown that the thermally induced desorption of the loaded carboxylic acids from the compound according to the invention is quantitative in a certain temperature range, while the carrier component is advantageously stable up to 300°C.

Differential thermal analysis (DTA), in which the temperature of a sample is compared to that of an inert reference material during a programmed temperature change, validated the control of the highly relevant endothermic processes for the compound of the invention, such as the evaporation of water to purify the compound of the invention and / or the Desorption, representing the release of the active substance. The examination of the weight changes (TGA signal) and the simultaneous detection of the caloric phenomena (DTA signal) are therefore a proof of concept for the successful acid release of the compound according to the invention.

It has been shown that the desorption of the charged acids of the compounds according to the invention requires a significant energetic excitation to release the charged acid(s) from the acid-charged carrier, eg by thermal energy input, compared to the isolated acid alone. The additional energy required to release the loaded carboxylic acid from the support structure clearly shows the stability of the compound according to the invention, which is based on the strength of the physisorption of the loaded carboxylic acid on the carrier structure. The substance is thus an inclusion compound.

The advantageously delayed evaporation or the increased thermal energy that is required to release the loaded carboxylic acid from the support structure thus demonstrates the stability of the compound according to the invention. The delayed release of liquid short-chain carboxylic acids by evaporation when loaded according to the invention effectively suppresses the uncontrolled release of the loaded short-chain acid by evaporation, so that complex cooling of the formulation at room temperature or complex sealing of the container used for storing the compound according to the invention is not necessary.

Organic acids and pK _a (general overview)

Organic acids are carbonaceous chemical compounds whose acidity is used in a variety of applications and is important to a wide range of manufacturing industries. The compound of the present invention embodies a loaded carboxylic acid in a dry state, thereby advantageously facilitating the control of its acidity. Since the present invention is primarily concerned with the acidity that resides in the first equilibrium of proton dissociation from a carboxyl group (-COOH), the pK _a1 values are particularly relevant.

des Metallgegenions gleich oder kleiner als der pK_a1 der beladenen Carbonsäure R²COOH oder einer beliebigen Mischung verschiedener R²COOH. Dabei wird die pK_a-Differenz der erfindungsgemäßen Bestandteile als treibende Reaktionskraft zur Erzeugung der Einschlussverbindung technisch ausgenutzt. Auf diesem Weg ist es nicht notwendig, vorgesehene Reaktionswege zur Erzeugung der erfindungsgemäßen Verbindung zu unterstützen, z.B. durch den Einsatz weiterer Zusatzstoffe, Reaktionspartner oder Katalysatoren. Da keine weiteren Zusatzstoffe, Reaktanten oder Katalysatoren benötigt werden, weisen die gewünschten Produkte eine höhere Reinheit auf, und eine Aufreinigung wird deutlich erleichtert. Außerdem werden die charakteristischen Eigenschaften der erhaltenen festen Produkte nicht durch sonst erforderliche Additive verändert.Strong acid-base reactions, such as those of the carrier carboxylic acids, are typically exothermic. According to the invention, the pK _a1 is the corresponding acid of the carrier ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

of the metal counterion equal to or less than the pK _a1 of the charged carboxylic acid R ² COOH or any mixture of different R ² COOH. In this case, the pK _a difference of the components according to the invention is used technically as the driving reaction force for generating the inclusion compound. In this way, it is not necessary to support intended reaction paths for producing the compound according to the invention, for example by using other additives, reactants or catalysts. Because no additional additives, reactants, or catalysts are required, the desired products are of higher purity and purification is greatly facilitated. In addition, the characteristic properties of the solid products obtained are not altered by additives that would otherwise be required.

carrier carboxylic acid salt

bezeichnet als Trägersäure, die bei einer Reaktion mit einer Erdalkalibase einen Säuresalzträger bildet. Erfindungsgemäß besitzt die Trägersäure einen niedrigeren pK_a-Wert bzw. eine stärkere Acidität als die auf den Träger zu beladenden Säuren, was vorteilhaft die in-situ-Erzeugung durch Neutralisation der Trägersäure zu dem korrespondierenden Salz unter Bildung der Trägerstruktur ermöglicht. Somit besitzt eine Trägersäure nach der Bildung der erfindungsgemäßen Einschlussverbindung keine Aktivität und dient als stabiler Träger für die beladene Säure.The solid compound of the present invention comprises a salt of a carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-},$

referred to as a carrier acid that forms an acid salt carrier when reacting with an alkaline earth metal base. According to the invention, the carrier acid has a lower pK _a value or a stronger acidity than the acids to be loaded onto the carrier, which advantageously enables in situ generation by neutralization of the carrier acid to the corresponding salt with formation of the carrier structure. Thus, once the inclusion complex of the present invention is formed, a carrier acid has no activity and serves as a stable carrier for the loaded acid.

des Metallgegenions gleich oder kleiner dem pK_a1 der beladenen Carbonsäure R²COOH oder einer beliebigen Mischung verschiedener R²COOH. Gemäß einer bevorzugten Ausführungsform der Erfindung ist die Differenz des pK_a1 (ΔpK_a1) zwischen der Trägercarbonsäure ${\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

und der entsprechenden beladenen Carbonsäure(n) R²COOH 0.1 ≤ ΔpK_a1 ≤ 5.0, vorzugsweise 0.2 ≤ ΔpK_a1 ≤ 4.0, besonders bevorzugt 0.3 ≤ ΔpK_a1 ≤ 3.0. Die darin definierte Differenz zwischen dem pK_a1 der entsprechenden Säure des Salzes der Trägercarbonsäure ${\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

und dem der beladenen Carbonsäure(n) R²COOH erhöht vorteilhaft die Stabilität der erfindungsgemäßen Verbindung. Diese erhöhte Stabilität ist für den Transport und die Lagerung der erfindungsgemäßen Verbindung von großem Vorteil. Darüber hinaus ermöglicht die bevorzugte pK_a-Differenz der erfindungsgemäßen Säure-Base-reaktiven Bestandteile vorteilhaft eine erhöhte Selektivität der vorgesehenen Reaktionswege, wodurch Nebenreaktionen unterdrückt werden.According to the invention, the pK is _a1 of the corresponding acid of the carrier ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

of the metal counterion equal to or less than the pK _a1 of the charged carboxylic acid R ² COOH or any mixture of different R ² COOH. According to a preferred embodiment of the invention, the difference in pK _a1 (ΔpK _a1 ) between the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

and the corresponding charged carboxylic acid(s) R ² COOH 0.1≦ΔpK _a1 ≦5.0, preferably 0.2≦ΔpK _a1 ≦4.0, particularly preferably 0.3≦ΔpK _a1 ≦3.0. The difference defined therein between the pK _a1 of the corresponding acid of the salt of the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

and that of the charged carboxylic acid(s) R ² COOH advantageously increases the stability of the compound according to the invention. This increased stability is of great advantage for the transport and storage of the compound according to the invention. In addition, the preferred pK _a difference of the acid-base-reactive components according to the invention advantageously enables increased selectivity of the reaction pathways provided, as a result of which side reactions are suppressed.

offenbart R¹, welche ausgewählt ist aus einer gegebenenfalls substituierten C₁-C₁₀-Alkylgruppe, oder einer gegebenenfalls substituierten Arylgruppe, wobei der Substituent ausgewählt ist aus einer Carbonylgruppe (=O), vorzugsweise umfassend eine Carbonylgruppe benachbart zu einer Hydroxygruppe unter Bildung einer Carbonsäuregruppe, einer Aminogruppe (NH₂), einer Hydroxygruppe (OH), einem Halogen oder einer Cyanogruppe.The carrier carboxylic acid according to the invention ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

discloses R ¹ which is selected from an optionally substituted C ₁ -C ₁₀ alkyl group, or an optionally substituted aryl group, wherein the substituent is selected from a carbonyl group (=O), preferably comprising a carbonyl group adjacent to a hydroxy group to form a carboxylic acid group , an amino group (NH ₂ ), a hydroxy group (OH), a halogen or a cyano group.

or $-{\text{C}}^{\mathrm{\beta }}{\text{R}}_3^3$

beschrieben, wobei C^ßdas ß-Kohlenstoffatom in Bezug auf die Carboxylgruppe ${\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

des Trägers ist. Bevorzugt ist R¹ ausgewählt aus der Formel -X, -C^ßX₃ oder -C^ßX₂R³. Noch bevorzugter ist erfindungsgemäß die Auswahl der Formel -X or -C^ßX₂R³ für R¹. Die darin bevorzugt für R¹ gewählten Gruppen stellen aufgrund einer verringerten Resonanzstabilisierung für die deprotonierte Trägercarbonsäureform vorteilhaft Trägercarbonsäuren mit erhöhter Acidität dar. Hierdurch wird eine hohe Ausbeute und eine hohe eine schnelle Säure-Base-Reaktivität der Trägercarbonsäure erreicht, wobei bei einer Neutralisation das entsprechende Trägercarbonsalz bzw. die Trägerkomponente entsteht. Die erhöhte Acidität verringert kinetisch Nebenreaktionen und macht eine Unterstützung der gewünschten Reaktionswege, z.B. durch weitere Zusätze, Reaktanten oder Katalysatoren, vorteilhaft überflüssig.According to the invention, R ¹ is represented by the formula -X, -C ^ß X ₃ or -C ^ß X ₂ R ³ or $-{\text{<figure-callout id="2" label="C β XR" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0045.png" state="{{state}}">C</figure-callout>}}^{\mathrm{\beta }}{\text{XR}}_{}^{}{}_2^3$

or $-{\text{C}}^{\mathrm{\beta }}{\text{R}}_3^3$

described, where C ^ß is the ß-carbon atom in relation to the carboxyl group ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

of the wearer. R ¹ is preferably selected from the formula -X, -C ^ß X ₃ or -C ^ß X ₂ R ³ . Even more preferred according to the invention is the selection of the formula —X or —C ^β X ₂ R ³ for R ¹ . The groups preferably selected therein for R ¹ are advantageously carrier carboxylic acids with increased acidity due to a reduced resonance stabilization for the deprotonated carrier carboxylic acid form. This achieves a high yield and high, rapid acid-base reactivity of the carrier carboxylic acid, with neutralization producing the corresponding carrier carboxylic salt or the carrier component is created. The increased acidity kinetically reduces side reactions and advantageously eliminates the need to support the desired reaction pathways, for example by means of further additives, reactants or catalysts.

According to the invention, R ³ groups can comprise an optionally substituted C ₁ -C ₁₀ -alkyl group or an optionally substituted aryl group. Preferably, R ³ is selected from a group consisting of an optionally substituted C ₁ -C ₈ alkyl group or an optionally substituted aryl group. Even more preferably, R ³ is selected from a group consisting of an optionally substituted C ₁ -C ₆ alkyl group or an optionally substituted aryl group. A beneficial technical effect results from the reduced alkyl chain length of R ³ , as defined above, since these structures have increased solubility in polar solvents. Good solubility in polar solvents, for example in water, is of great importance for every technical reaction path and production process and is advantageous for the use of carrier carboxylic acid salts in industry.

The substituent of R ³ according to the invention can be an amide group, an ester group, an ether group, a thioether group, a carbonyl group (=O), preferably comprising a carbonyl group adjacent to a hydroxy group to form a carboxylic acid group, an amino group (NH ₂ ), a hydroxy group (OH ) or an X group, where X is selected from fluorine (F), chlorine (Cl) or bromine (Br). The substituent of R ³ is preferably selected from a carbonyl group (=O), preferably comprising a carbonyl group adjacent to a hydroxy group to form a carboxylic acid group, an amino group (NH ₂ ) or a hydroxy group (OH). The substituent of R ³ is preferably selected from a carbonyl group (=O) comprising a carbonyl group adjacent to a hydroxy group to form a carboxylic acid group, an amino group (NH ₂ ) or a hydroxy group (OH).

The substituents X can be selected from hydrogen (H), hydroxy (OH), fluorine (F), chlorine (Cl), bromine (Br) or another electron withdrawing functional group such as cyano (CN). Preferred substituents for X are selected from hydrogen (H), hydroxy (OH), fluorine (F), chlorine (Cl) or another electron withdrawing functional group such as cyano (CN). Hydrogen (H) or a hydroxy group (OH) is particularly preferably selected for X according to the invention. The substituents for X selected herein include structures that are relatively inexpensive to synthesize and/or occur naturally and/or have the greatest industrial importance.

An example of the more preferred carrier carboxylic acid components of the invention is given when R ¹ is selected by -X and a hydrogen (H) is selected for -X, representing formic acid. Further examples of more preferred carrier carboxylic acids are given when -C ^β R ³ X ₂ is selected for R ¹ and X are selected from hydrogen (H) or a hydroxy group (OH) which form preferred secondary C _β atoms. The formula defined here includes more preferred carrier acids of the invention with great importance for industrial products such as acetic acid, propionic acid, lactic acid, glycolic acid, butyric acid, succinic acid, fumaric or maleic acid, adipic acid, malic acid, malonic acid, tartaric acid, aspartic acid, glutamic acid, benzoic acid, salicylic acid and citric acid .

(Figur unten, gesamter Kasten), die Formel der am meisten bevorzugten Trägercarbonsäure, die durch die Wahl der Formel -X oder -C^ßX₂R³ für R¹ definiert ist, und Beispiele für letztere (Figur unten, rechts).

The following figure shows the general formula of the salt of the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

(Figure below, entire box), the formula of the most preferred carrier carboxylic acid defined by the choice of formula -X or -C ^β X ₂ R ³ for R ¹ and examples of the latter (Figure below, right).

Since the carrier carboxylic acid must have a lower pK _a value than the loaded carboxylic acid(s), which preferably include formic acid, acetic acid, propionic acid, lactic acid, glycolic acid and butyric acid, a wide selection of pairs of carrier acids is advantageous, which is a versatile platform for carboxylic acid loaded carboxylic acid salt supports.

Carrier carboxylic acids according to the invention may include carboxylic acids which are solid at room temperature, selected from arachidic acid, stearic acid, palmitic acid, myristic acid, enantic acid, caprylic acid, oxalic acid, aspartic acid, glutamic acid, malonic acid, tartaric acid, salicylic acid, fumaric or maleic acid, citric acid, malic acid, ascorbic acid , succinic acid, benzoic acid, adipic acid, formic acid, glycolic acid, lactic acid, acetic acid, butyric acid and propionic acid. Preferred carboxylic acid carriers according to the invention are selected from enanthic acid, caprylic acid, oxalic acid, aspartic acid, glutamic acid, malonic acid, tartaric acid, salicylic acid, fumaric or maleic acid, citric acid, malic acid, ascorbic acid, succinic acid, benzoic acid, adipic acid, formic acid, glycolic acid, lactic acid, acetic acid, butyric acid and propionic acid . According to the invention, carboxylic acid carriers are particularly preferably selected from aspartic acid, glutamic acid, malonic acid, tartaric acid, salicylic acid, fumaric or maleic acid, citric acid, malic acid, ascorbic acid, succinic acid, benzoic acid, adipic acid, formic acid, glycolic acid, lactic acid, acetic acid, butyric acid and propionic acid, the last six are liquid at room temperature. The carboxylic acids selected herein have reduced hydrophobicity over longer chain linear carboxylic acids. Therefore, the carboxylic acid carriers according to the invention are preferably soluble in polar solvents, which enables easy handling and manufacture. For example, compounds of the invention comprising citrates have been shown to significantly improve growth performance in aquaculture fish (Reviews in Aquaculture, 2017).

In addition, the use of the ascorbate carrier according to the invention in combination with loaded acetic acid is suitable, for example, for use as a color-retaining agent in food and feed applications. The loaded acetic acid in the compounds of this invention acts beneficially as an acidulant (pH control that mitigates myoglobin oxidation). A compound of the present invention containing derivatives of ascorbic acid (vitamin C) advantageously provides the vital functions of ascorbic acid because, as an antioxidant, it can protect cellular components from free radical damage.

The pK _a1 values of a selection of the preferred carrier carboxylic acid according to the invention are listed in Table 1 below, with a liquid state at room temperature being marked by an asterisk:

Table 1. A selection of preferred carrier carboxylic acids according to the invention and their pK _a1 values, a liquid state at room temperature being marked by an asterisk (*). acid pK _a1 aspartic acid 1.99 glutamic acid 2.16 malonic acid 2.83 tartaric acid 2.98 salicylic acid 2.75 fumaric acid 3.00 citric acid 3.09 malic acid 3.40 formic acid* 3.77 glycolic acid* 3.83 lactic acid* 3.86 ascorbic acid 4.25 succinic acid 4.19 benzoic acid 4.20 adipic acid 4.43 Acetic acid* 4.76 butyric acid* 4.82 propionic acid* 4.88

Changing the _pKa of organic acids is generally possible by changing the alkyl chain length or functional substituents along the alkyl chain. In general, the pK _a of organic acids decreases only slightly with alkyl chain length. A more effective modification of the pK _a of organic acids is possible by suitable substituents affecting the acidity of the carboxyl group, preferably at the C ^ß atom of the latter, which is the case for X.

In one embodiment of the invention X is selected from a hydrogen (H) or an electron withdrawing group selected from fluorine (-F), chlorine (-Cl), bromine (-Br), iodine (-I) or cyano (-CN) . In a preferred embodiment of the invention X is selected from a hydrogen (H) or an electron withdrawing group selected from fluorine (-F), chlorine (-Cl), bromine (-Br) or cyano (-CN). In a preferred embodiment of the invention X is selected from hydrogen (H) or an electron withdrawing group selected from fluorine (-F), chlorine (-Cl) or cyano (-CN).

The substituents X on the C ^ß of the carrier carboxylic acid selected in the embodiment according to the invention have a higher electron negativity (EN) than a carbon EN _c and bring about inductive electron withdrawal, as a result of which the acidity of the carrier carboxylic acids is increased. Therefore, the pK _a1 of the carrier carboxylic acids is advantageously reduced in the preferred embodiment of the invention, which is even more pronounced for substituents X with a higher electronegativity with respect to EN _c in the order (F>CI>Br>I) and in the preferred embodiment of the invention is taken into account.

The increased acid strength when selecting X according to the (further) preferred embodiment of the invention advantageously allows a wider selection of pairs of carrier acid and acid to be loaded, while the pK _a of the carrier carboxylic acid compared to the loaded carboxylic acid according to the Criteria of the invention is lower. Lowering the pK _a1 by functional β-substituents thus opens avenues for new compounds of loading/loaded acids.

(Figur unten, gesamter Kasten), Strukturen der durch R¹ definierten Ausführungsform der erfindungsgemäßen Trägercarbonsäure (Figur unten, gestrichelter Kasten) und Beispiele für die letztere (Figur unten, rechts). Die Strukturen der weiter bevorzugte Auswahl sind in Analogie zu den obigen Beispielen dargestellt.

The following figure shows the general formula of the carrier carboxylic acid salt ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

(Figure below, entire box), Structures of the embodiment of the carrier carboxylic acid according to the invention defined by R ¹ (Figure below, dashed box) and examples of the latter (Figure below, right). The structures of the more preferred selection are shown in analogy to the above examples.

In addition, modification of the acidity of the carrier carboxylic acid through targeted selection of the substituents X enhances the above advantages by increasing the pK _a1 difference between the carrier acid and the loaded acid. As a result, increased stability, increased safety of the acid-loaded carboxylic acid salt carrier for transport and storage, and increased selectivity and/or reaction rate of the acid-base reaction are advantageously achieved.

Loaded acids and pK _a

The acid-reactive component of the compound of the invention comprises the charged carboxylic acid(s) R ² COOH, referred to as the charged acid, where R ² may comprise an optionally substituted C ₁ -C ₁₀ alkyl group or an optionally substituted aryl group , preferably R ² is selected from an optionally substituted C ₁ -C ₈ alkyl group or an optionally substituted aryl group, more preferably R ² is selected from an optionally substituted C ₁ -C ₄ alkyl group or an optionally substituted aryl group. The preference for the charged acid as short chain carboxylic acids in this invention, most preferably a C ₁ -C ₄ having an alkyl chain length of less than five carbon atoms, is related to its liquid state at rt. Therefore, liquid carboxylic acids such as formic acid, acetic acid, glycolic acid, propionic acid, butyric acid and lactic acid can be handled according to the invention in powder form, which is of great importance for safety and advantageously does not require dilution. These aspects are of great importance for the liquid short-chain carboxylic acids mentioned when they are used in the pharmaceutical, cosmetics, food and animal feed industries.

The substituents of R ² can be selected from hydrogen (H), a carbonyl group (=O), which preferably contains a carbonyl group adjacent to a hydroxy group to form a Car carboxylic acid group, an amino group (NH ₂ ), a hydroxy group (OH), a halogen including fluorine (-F), chlorine (-Cl), bromine (-Br), iodine (-I), or cyano group (-CN) includes, or a mixture thereof. Preferred substituents of R ² are selected from hydrogen (H), a carbonyl group (=O), preferably comprising a carbonyl group adjacent to a hydroxy group to form a carboxylic acid group, hydroxy group (-OH) or a mixture thereof. According to the invention, hydrogen (H) or a hydroxy group (OH) or a mixture thereof is particularly preferably selected as the substituent of R ² . The most preferred substituents for R ² according to the invention include carboxylic acids which are naturally abundant and/or relatively inexpensive to synthesize and which are of great industrial importance. Furthermore, these charged acids advantageously do not comprise any basic groups such as the amino group (NH ₂ ) which would interfere with the acid-reactive character provided according to the invention.

Examples of preferred loaded carboxylic acids according to the invention are shown in the following figure and include short chain C ₁ -C ₄ carboxylic acids such as formic, acetic, glycolic, propionic, lactic and/or butyric acid or a mixture thereof, which advantageously are biocompatible and bioavailable as described above.

The pK _a values of the first acid of the short-chain R ² COOH carboxylic acids preferably used are given in Table 2 below:

Table 2. The short-chain R ² COOH carboxylic acids preferably used according to the invention and their pK _a values. acid pK _a1 formic acid 3.77 glycolic acid 3.83 lactic acid 3.86 acetic acid 4.76 butyric acid 4.82 propionic acid 4.88

The preferred loaded acids advantageously have high acidity and are thus effective acidulants for a wide range of industrial applications where control of reactivity is required for storage, transportation and safety to facilitate their economical handling, as illustrated by the invention is possible.

Hierdurch kann eine breite Palette von Carbonsäure-beladenen Carbonsäuresalz-Trägerkombinationen erzeugt und angepasst werden.With regard to the criterion of the pK _a difference of the carrier acid and the acid loaded according to the invention, the pK _a of the loaded carboxylic acids advantageously enables the selection of several ligand counterions ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}.$

In this way, a wide range of carboxylic acid-loaded carboxylic acid salt carrier combinations can be generated and adapted.

These acid-loaded carriers are advantageous for a wide range of applications. The compound of the invention has been found to be useful as an antimicrobial preservative in cosmetic, pharmaceutical, food and feed applications. In addition to antimicrobial, preservative and sanitary functions, carboxylic acids such as formic acid and formates together with propionic acid and propionates have shown significant zootechnical efficacy in fattening pig weight gain (Nutrition Research Reviews, 1999).

The compound according to the invention is also suitable for use as a nutraceutical additive in human and animal food supplements, for example when the compound is charged with lactic acid the is. Lactic acid, like other food supplements, is a natural substance that can be extracted from biological sources and can therefore provide important health benefits when incorporated into the compound of the invention, eg as an additive when included in the food matrix.

In a preferred embodiment of the invention, the compound according to the invention can be built up from one and the same acid or from a mixture of charged carboxylic acids R ² COOH. A compound comprising multiple loaded carboxylic acids R ² COOH allows the overall acid strength of the acid-loaded support to be tailored. The Federation Europeenne des Fabricants d'Adjuvants pour la Nutrition Animale expressly recommends the combination according to the invention of such carboxylic acids with medium-chain fatty acids to increase growth performance.

A variety of synthesis routes according to the invention with formate as a carboxylic acid carrier, which is loaded with carboxylic acids such as lactic, acetic and butyric acid, advantageously leads to compounds that comply with the EU Feed Additives Regulation and fulfill a variety of functions, and from hygiene control to preservation to Encouraging growth is enough.

Ratio of loading acid or salt to carrier acid(s)

The molar ratio of loaded carboxylic acid to carrier carboxylic acid salt n is important as it advantageously defines the ratio of reactive component to carrier components. Therefore, n advantageously fixes the concentration of the acid(s) in the compound of the invention and facilitates tailoring of reactivity for the end use.

Typically, the ranges of the molar ratio include 0.1≦n≦10, preferably according to the invention n includes 0.5≦n≦8, particularly preferably n is selected according to the invention in the range 1≦n≦6. It has been shown that compounds which have a molar ratio n within the ranges preferred according to the invention have a high acid activity and are stable at the same time. This allows the carboxylic acid to be loaded on the carboxylic acid salt carrier loaded with carboxylic acid and/or a high molar concentration of the carboxylic acid is possible, which makes economic transport, storage and use possible, taking safety aspects into account.

In addition, the change in the ratio n, ie the variation in the molar ratio of the starting materials used in the process according to the invention, can be adapted in a simple manner.

Polarity / dipole character / hydrophilic-lipophilic balance

A support and a loaded component of an inclusion complex must exhibit a certain attractive interaction or cohesion to enable the required physisorption, which may be related to the polarity of the organic acid components.

The concept of polarity refers to the separation of charges that can induce a dipole moment, e.g. between atoms in a covalent bond or between two ions with opposite charges. In general, dipole moments arise from differences in the electronegativity EN. This means that the carbonyl group (-C=O), the carboxylic acid (-COOH), the amino group (-NH ₂ ), or the hydroxy group (-OH) affect the overall polarity of substituted carboxylic acid moieties, since the EN of the heteroatoms differ significantly from the EN _C of the carbons differs.

It is true that the overall polarity or the dipole moment influences important parameters such as the solubility, the state of aggregation and the stability of the acid-loaded carrier compound of the present invention.

A suitable and simple descriptor for the indication of the net polarity of the organic acids according to the invention is the ratio of polar groups, for example from hydrophilic groups such as a carbonyl group (-C = O), carboxylic acid (-COOH), amino group (-NH ₂ ) or Hydroxy group (-OH) to lipophilic organic groups such as (-CH ₁ -, -CH ₂ -, -CH ₃ -, and =CH ₁ -). For convenience, the length of the alkyl chain relative to the number of polar/hydrophilic groups or organic acid is a useful indicator of the tendency of an organic acid to exhibit polar changes to possess self-acting forces and thus to assess, predict and control the properties relevant to the invention.

The adjustable overall polarity of the components according to the invention through the choice of components with a specific lipophilic/hydrophilic character is of great advantage for their use in emulsion formulations. The compound according to the invention is therefore advantageous, for example, as an active ingredient in cosmetic and pharmaceutical applications, in particular for acid regulation in pH-defined skin cleansing products, for supporting the cleaning effect in shaving soaps or for supporting disinfection in washing lotions.

It has been shown that increased stability of the compound according to the invention is achieved through the combination of components with high polarity, based on derivatives that include lipophilic groups. Since increased stability correlates directly with safety aspects of the connection according to the invention, the simple estimation of the polarity of the components advantageously enables a structural design of connections with defined stability or handling safety. In this way, tailored connections can be selected according to the polarity characteristics of the individual components to take account of individual transport and storage conditions. For example, overseas transport may require more stable connections than short-term transport.

The overall polarity of the components according to the invention is necessarily linked to the tendency of the components to absorb water, i.e. hygroscopicity. Since water is a by-product released during the course of the process of the invention, estimation of the overall polarity of the components predicts the conditions for drying the acid-loaded support, e.g., whether extensive drying under reduced pressure or at an elevated temperature is required. This assessment is of great relevance for the economic planning of the production method according to the invention.

The prediction of the hygroscopicity also facilitates the targeted selection of suitable containers and the effective suppression of the accumulation of water molecules between the molecules of the component. This advantageously mitigates physical changes in the compound of the invention, e.g., changes in volume, boiling point, viscosity, or other physical properties.

Flowability (based on size & cohesion or polarity or hygroscopicity)

The present invention provides a solid inclusion compound which is produced as a powder and has good flowability. Flowability describes the relative mobility of a mass of particles among neighboring particles and relates to the ability of a powder to flow.

The good flowability achieved by the powdered carrier systems of the present invention advantageously enables good powder product quality, manufacturing efficiency, transport safety and storage for a wide field of the powder processing industry. In addition to the general influences on the flowability, such as the bulk density and the cohesion properties of the components within the inclusion compound, the particle size and the particle size distribution have a major influence on the flowability of powders (see Baker et al., 1979), as explained below.

particle size

The particle size and the particle size distribution serve as suitable indicators for the flowability of the carboxylic acid-loaded carboxylic acid salt carrier. The particle size of a powder mixture is typically defined by the mean particle diameter d _av , ie the diameter of most of the particles present in a given particle size distribution of a powder. Typically, the average particle diameter d _av of the free-flowing powder has an average particle diameter of 10 μm _≦ d _av ≦5,500 μm; according to the invention, an average particle diameter in the range of 20 μm _≦ d _av ≦5,300 μm is preferred, and an average particle diameter is particularly preferred according to the invention Particle diameters in the range of 50 µm _{≤d av} ≤ 5,250 µm.

It has been found that the particle size range preferred therein ensures optimal flowability of the compound of the invention, enabling the multitude of flowability advantages described above, while at the same time advantageously reducing the presence of aerosol particles. Aerosol particles are typically a few nanometers in diameter and tend to form heterogeneous mixtures with the surrounding gas, eg air, which is harmful if the suspended particles are inhaled through the lungs. It has been shown that if the compound according to the invention has preferred size ranges as indicated above, the formation of undesired aerosols is advantageously avoided. Therefore, the compound according to the invention supports health protection when it comes into contact with living beings during processing and handling.

It has also been shown that the preferred diameter range facilitates optimal loading of the particles of the compound according to the invention. Typically, the amount of components that can be loaded onto a particulate carrier increases as the bulk diameter of the particles decreases, based on the increase in the relative surface area of the carrier particles. Therefore, the preferred size range supports primarily flowability and secondarily high loading capacity while avoiding aerosol properties of the particles.

particle size distribution

In addition to the particle size, the particle size distribution serves as a suitable indicator for the flowability of the carboxylic acid salt carrier loaded with carboxylic acid. The particle size distribution of a powdered compound is generally described by the mean particle diameter (d _X0 ), which defines the proportion of particles with a specific diameter smaller or larger than the value X0 _vol %.

The particle diameter distribution d ₅₀ of the compound according to the invention can be 10 μm≦d ₅₀ ≦500 μm, preferably 20 μm≦d ₅ ≦300 μm and is particularly preferably selected from 50 μm≦d ₅₀ ≦250 μm.

The particle diameter distribution defined therein represents a low dispersity of the particle size of the flowable powder according to the invention. A low dispersity of the particle size as an essential factor for the flowability of the pulverulent carrier compound according to the invention advantageously enables a good powder product quality. If the compound according to the invention is used, for example, in the pharmaceutical industry, the powder flow behavior predetermined by the particle size distribution enables, for example, a defined filling weight and uniform content of pharmaceutical preparations.

According to the invention, a narrow size distribution is advantageous and at least 50% by weight, preferably at least 90% by weight, of the powdered, acid-loaded salt carrier has a particle diameter of less than 450 μm. The narrow size distribution described therein is defined by the d ₉₀ . The particle diameter distribution d ₉₀ of the compound according to the invention is 10 μm≦d ₉₀ ≦1000 μm, preferably 50 μm≦d ₉₀ ≦800 μm, particularly preferably 150 μm≦d ₉₀ ≦450 μm.

The particle diameter distribution d ₉₀ defined therein enables even greater uniformity compared to the parameter d ₅₀ for the powdered salt carrier loaded with C ₁ -C ₄ carboxylic acid. In addition to the benefits of a defined d ₅₀ , the preferred ranges for d ₉₀ values support efficiency and safety for any powder processing manufacturing process. For example, gravity feed and consistent and precise powder dosing is facilitated on a commercial scale, as evidenced by diffraction granulometry for the compounds. For example, regular powder flow from vertical bins or silos for size-dependent storage of acid-laden salt carriers avoids capacity bottlenecks and production disruptions that would otherwise result in costly production downtime.

The base

According to the invention, the support carboxylic acid is reacted with a base to form the acid salt support. In this invention, the term "base" is applicable to a variety of bases. Usually, hydrated inorganic bases or more appropriate bases consisting of metal cations with positive charge M ¹⁺ , double positive charge M ²⁺ or triple positive charge M ³⁺ are chosen for the acid-base reactions. The most satisfactory results for the compound of the invention are obtained from bases which include divalent metal bases M ²⁺ .

The divalent metal ion M ²⁺ is typically selected from the group consisting of iron (Fe), copper (Cu), zinc (Zn), manganese (Mn), tin (Sn), lead (Pb), nickel (Ni) or one alkaline earth metal ion, preferably such as calcium (Ca), magnesium (Mg), barium (Ba) or a mixture thereof. Divalent metal ions carry a double positive charge, which is advantageous for the composition and the stoichiometry of the compound according to the invention.

According to the invention, M ²⁺ is preferably selected from iron (Fe) or an alkaline earth metal ion, preferably calcium (Ca), magnesium (Mg), barium (Ba), or a mixture thereof. The preference of the divalent metal ions selected herein for the compound of the invention is based on their bioavailability, where the abundance of occurrence in nature is profitable.

Even more preferably, M ²⁺ according to the invention is selected from an alkaline earth metal ion, preferably calcium (Ca), magnesium (Mg) or a mixture thereof. Aside from the advantages of using calcium or magnesium in terms of their favorable stoichiometry, calcium or magnesium exhibit bioavailability and biocompatibility. In addition, they are essential in biochemical processes, since magnesium is important, for example, for neurogenerative processes such as muscle contraction, for blood clotting or for vitamin absorption, while calcium is an important building block of bones and teeth. Therefore, the incorporation of calcium or magnesium into the carrier acid/salt structure enables the production of a digestible compound useful as a dietary supplement to improve human and animal health. An example of a digestible compound of the invention having health benefits is provided by compounds of the invention containing calcium or magnesium citrate. The use of the compounds according to the invention is therefore suitable as a zootechnical additive in animal nutrition, for example as an acidifier for the gastrointestinal tract or as a non-antibiotic growth promoter.

The use of a compound of the invention, particularly with alkaline earth metal ions such as Ca and/or Mg, is useful as a flavor and palatability agent in pharmaceutical, food and feed applications. An acid acetate-loaded carrier of the present invention can be used, for example, to impart a salty and vinegary flavor to potato chips or salad dressings. The compound according to the invention can replace conventional formulations with potassium or sodium diacetate and thus offers an alternative to the alkaline formulations in cosmetic products that are only permitted to a limited extent in the EU according to the European Commission.

Almost any calcium or magnesium base can be used in the reaction with the carrier carboxylic acid to form the acidic salt carrier. In a preferred embodiment of the invention, however, the alkaline earth metal base is selected from calcium hydroxide (Ca(OH) ₂ ), calcium oxide (CaO), calcium carbonate (CaCO ₃ ), magnesium oxide (MgO), magnesium hydroxide (Mg(OH) ₂ ) or magnesium carbonate (MgCO ₃ ), which advantageously serve as inexpensive starting materials for the synthesis of the compound according to the invention.

Oxid (O²-) oder Hydroxid (OH^-), die bei der exothermen Säure-Base-Reaktion zwischen der Trägercarbonsäure und der Metallbase zur Bildung des erfindungsgemäßen Säuresalzträgers freigesetzte Reaktionswärme.The choice of the alkaline earth metal base used determines the type and amount of the condensate liberated in the acid-base reaction between the carrier carboxylic acid and the metal base to give the acidic salt carrier according to the invention, which is formed as a by-product. Furthermore, the counterion of the alkaline earth metal base, eg carbonate, determines $\left({\text{CO}}_3^{2-}\right),$

Oxide (O ² -) or hydroxide (OH ^- ), the heat of reaction liberated in the exothermic acid-base reaction between the support carboxylic acid and the metal base to form the acid salt support of the invention.

The use of alkaline earth metal carbonate as the starting material leads, for example, to a significant release of heat in the immediate and exothermic formation of CO ₂ , which can be used, for example, to facilitate the drying process. The choice of the alkaline earth metal base used thus makes it possible to adjust the thermal conditions of the process according to the invention. In addition, the released gaseous carbon dioxide advantageously supports the thorough mixing within a reaction vessel and can be used as a reliable indicator for the completion of the acid-base reaction. The use of alkaline earth metal hydroxides and oxides as bases is a preferred embodiment according to the process of the invention, with water being formed as a by-product.

If water is released as a by-product, the water of condensation formed creates microcompartments between the particulate components consisting of the carrier carboxylic acid and the metal base and improves the reaction environment for the acid-base reaction, since the water of condensation serves as a solvent for the remaining reactants that have not yet reacted. Subsequently, the presence of water as a by-product serves to create microcompartments with an accelerated reaction rate, promoting complete conversion of the reactants. The in-situ generation The use of water as a solvent is particularly important for the preferred solvent-free reaction processes, since it compensates for possible poor mixing or poor contact between the reactants.

In summary it can be said that the compound according to the invention is based on inexpensive starting materials and contains exclusively organic components, namely carboxylic acids and/or carboxylic acid salts, and an alkaline earth metal base which advantageously has biocompatibility and/or digestibility. Furthermore, since no additives or catalysts are required, organic acids can be processed economically on an industrial scale.

Advantages and description of the procedure

General processing of loaded acids

The loaded carboxylic acid(s) can be loaded onto the support in various ways. In general, all methods that allow intimate contact between the components forming the carboxylic acid salt carrier are suitable to obtain a homogeneous, free-flowing, non-caking compound according to the invention. The components must have sufficient flowability for good dispersion, so that the carboxylic acid to be loaded is distributed essentially uniformly when they come into contact with one another.

The carrier salt can be loaded with the loaded carboxylic acid(s) in various ways. Typically, the particles are contacted in the gas phase by passing an inert gas capable of evaporating any liquid components upon atomization through a mass of the particles in a fluidized bed apparatus. Alternatively, the particles can be positioned on a static or moving sieve device.

Method of the Invention

The present invention comprises the loading of the carrier salt particles, preferably without a solvent, by the simultaneous generation of the carrier salt from the corresponding acid and by the in situ inclusion of the loaded carboxylic acid(s) in the carrier structure. The compound according to the invention is obtained by a simple preparation process which comprises mixing the carrier carboxylic acid, the loaded carboxylic acid(s) and the alkaline earth metal base and then drying the compound obtained while controlling the temperature, humidity and particle size.

entweder mit der Base vorgemischt wird, genannt Ex-post-Verfahren, oder weiter bevorzugt mit der beladenen Carbonsäure R²COOH vorgemischt wird, genannt In-situ-Verfahren. Bei beiden bevorzugten Ausführungsformen des erfindungsgemäßen Verfahrens muss die exotherme Säure-Base-Reaktion, bei der es sich um eine Umsalzung zwischen der Erdalkalimetallbase und dem Trägercarbonsäure unter Bildung der Trägerstruktur handelt, neben der Beladung derselben mit der/den kurzkettigen Carbonsäure(n) durchgeführt werden.A process has been found for preparing the carboxylic acid salt carrier according to the invention, loaded with carboxylic acid, in which the starting materials, consisting of the carrier carboxylic acid, the loaded carboxylic acid and the alkaline earth metal base, are gently mixed, the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

is either premixed with the base, referred to as the ex post process, or more preferably premixed with the charged carboxylic acid R ² COOH, referred to as the in situ process. In both preferred embodiments of the method according to the invention, the exothermic acid-base reaction, which is a salt exchange between the alkaline earth metal base and the carrier carboxylic acid to form the carrier structure, must be carried out in addition to loading the same with the short-chain carboxylic acid(s). .

vorgemischt. Dieses Gemisch wird unterhalb des Siedepunktes der am meisten flüchtigen Verbindung gerührt, bis das Trägercarbonsäuresalz ${\text{M}}^{2+}{\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

entsteht und die Homogenität der Trägerverbindung erreicht ist. Das homogene Gemisch wird vor der Zugabe der beladenen Carbonsäure R²COOH getrocknet, gesiebt und anschließend unterhalb des Siedepunkts der flüchtigsten vorhandenen Verbindung gerührt, bis die Homogenität der Verbindung erreicht ist. Schließlich wird das erhaltene Gemisch ein zweites Mal getrocknet, vorzugsweise gefolgt von einer Zerkleinerung und Absiebung des erhaltenen Pulvers. Der Vorteil des Ex-post-Verfahrens liegt in der zwischenzeitlichen Trocknung und dem Sieben, wodurch die zwischenzeitliche Zerkleinerung und Reinigung erleichtert wird und somit der Aufwand für diese Schritte am Ende des erfindungsgemäßen Verfahrens vorteilhaft verringert wird. Daher ist das Ex-post-Verfahren in Fällen bevorzugt, in denen die Verbindungen umfangreich gemahlen werden müssen.The ex-post method is a preferred method for preparing the compounds of the present invention. First, the alkaline earth base and the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

premixed. This mixture is stirred below the boiling point of the most volatile compound until the carrier carboxylic acid salt ${\text{M}}^{}$${}^{2+}{\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

arises and the homogeneity of the carrier compound is reached. The homogeneous mixture is dried before addition of the loaded carboxylic acid R ² COOH, sieved and then stirred below the boiling point of the most volatile compound present until the compound is homogeneous. Finally, the mixture obtained is dried a second time, preferably followed by crushing and sieving of the powder obtained. The advantage of the ex-post process lies in the intermediate drying and sieving, which facilitates the intermediate comminution and cleaning and thus the effort for these steps at the end of the process according to the invention rens is advantageously reduced. Therefore, the ex-post method is preferred in cases where the compounds have to be extensively ground.

als Ausgangsmaterial eingekauft, vorgelegt, und mit der Carbonsäure R²COOH beladen. Diese Ausführungsform des bevorzugten erfindungsgemäßen Verfahrens ist geeignet, wenn die Trägercarbonsäure kostengünstig verfügbar ist oder wenn die Bestellungsmengen für die erfindungsgemäße Verbindung schwanken.In one embodiment of the preferred process of the invention, the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

purchased as starting material, submitted, and loaded with the carboxylic acid R ² COOH. This embodiment of the preferred process of the invention is useful when the carrier carboxylic acid is available at low cost or when order quantities for the compound of the invention fluctuate.

und die zu ladende Carbonsäure R²COOH vorgemischt, bis eine Homogenität der Mischung erzielt ist. Nach der anfänglichen Säuremischung wird die Erdalkalimetallbase, die das Erdalkalimetallion M²⁺ enthält, zu dieser unterhalb des Siedepunkts der flüchtigsten vorhandenen Verbindung rührenden Mischung von Carbonsäureverbindungen zugegeben. Schließlich wird die erhaltene Mischung getrocknet, vorzugsweise gefolgt von dem Mahlen und dem Sieben des erhaltenen Pulvers.Another preferred embodiment of the process of the invention for preparing the compound of the invention comprises an initial acid mixture in which all the compounds are added simultaneously, the so-called in situ process. In the in situ method, the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

and the carboxylic acid R ² COOH to be charged are premixed until the mixture is homogeneous. After the initial acid mixture, the alkaline earth metal base containing the alkaline earth metal ion M ²⁺ is added to this mixture of carboxylic acid compounds stirring below the boiling point of the most volatile compound present. Finally, the mixture obtained is dried, preferably followed by grinding and sieving the powder obtained.

The in situ generation of the compound of the invention advantageously allows the synthesis of the support while it is being milled with the acid to be loaded, thereby allowing effective incorporation of the acid to be loaded, resulting in a high carboxylic acid loading compared to the ex post procedure. Furthermore, it is advantageous that an intermediate drying step, as is required in the ex-post method, is superfluous in the in-situ method according to the invention.

However, all components (base, ligand acid and charged/free acid) can technically be added in any order in a reaction vessel, since it is to be expected that the components will form the desired product of the invention by salt exchange, depending on their chemical properties.

The starting materials

According to the method according to the invention, the starting materials are preferably used in a concentrated form, which has an advantageous effect on the effective probability of reaction, the shortening of the reaction time and the entire production process. Liquid acid concentrations above 70% are therefore preferred, acid concentrations greater than 95% are even more preferred. Suitable concentrations of the liquid starting materials are known to those skilled in the art with reference to good laboratory practice.

Those skilled in the art know that solid starting materials are preferably dry and of homogeneous particle size. Furthermore, it is known to the person skilled in the art that small particle sizes are preferred in mixing reactions in order to allow a maximum surface area of the starting materials and the greatest possible homogeneity of the mixture. The preferred particle sizes and size distributions advantageously minimize the mechanical energy expenditure for mixing in a reaction in the dry state.

temperature

The mixing of short chain carboxylic acids is generally carried out in a temperature range between 0°C<T<25°C, preferably between 0°C<T<20°C, most preferably between 5°C<T<15°C below the boiling point all components carried out under atmospheric pressure. Adherence to the preferred temperature ranges during the process according to the invention advantageously prevents evaporation of the starting materials and undesired solidification when the reaction mixture freezes.

However, the present invention is not restricted to the temperature range preferred for the process according to the invention. Other temperature ranges can be used, for example, to release a defined amount of loaded acids, so that the degree of loading with carboxylic acids can be adjusted individually. The amount of residual loaded carboxylic acid can be quantified from the liberated carboxylic acid, e.g., by thermal analysis such as thermogravimetric analysis (TGA).

mixing conditions/time

In addition to the temperature control, gentle addition of the starting materials of the exothermic acid-base reaction in the course of the process according to the invention advantageously avoids high thermal energy inputs from the heat of reaction released. This advantageously controls the reaction conditions, ensures the safety of the manufacturing process and avoids caking of the product.

In general, the particles are in contact with one another for a period of time sufficient to complete the acid-base reaction and physically load the particles with the intended amount of the loaded carboxylic acid of the invention. The reaction time of the method according to the invention is typically limited to a minimum time until the reaction is complete, which is generally less than 150 minutes, preferably less than 90 minutes and more preferably less than 20 minutes. However, the optimal reaction time depends heavily on the starting materials and the batch size used as well as the apparatus used.

The reaction time of the process according to the invention defined therein advantageously suppresses an uncontrolled release of the loaded acids, caking, entry of moisture or undesirable post-reaction temperature increase due to mechanical energy input during mixing. The controlled mechanical energy input is also supported by gentle and uniform mixing, which advantageously reduces agglomerations or poor flow properties of the product according to the invention.

water content and agglomeration

Agglomeration, i.e. the process in which many small particles accumulate to form larger macrostructures, is effectively suppressed by reducing the amount of water present. In the acid-base reaction to form the carrier salt structure, water may inevitably be formed if water is released as a condensate, for example when using a hydroxyl alkaline earth metal base. The water content is typically analyzed using a method based on the Karl Fischer titration according to ISO 760:1978 (cf. U.S. 4,703,014 ). It is characteristic that particulate powder formulations contain less than 15.0% by weight of water. Preferably the water content of the particulate acid-loaded carrier composition of the invention is less than 10.0% by weight, more preferably less than 5.0% by weight to provide a flowable acid-loaded carrier composition of the invention. Advantageously, the mitigation of agglomeration due to the limited amount of water in the product of the present invention facilitates the avoidance of otherwise encountered serious problems, notably poor flowability, difficult powder loading and deteriorated particle size uniformity.

The TGA diagram of a compound obtained from the process according to the invention, magnesium formate with loaded propionic acid (MgFo-HProp [2], see ), confirms the low water content, since no water is released when the sample is constantly heated in a temperature range from 1°C to 300°C.

However, the compound according to the invention does not have to be completely anhydrous. As long as the amount of water does not exceed the amount of water required for agglomeration of the particles, which is an individual parameter with regard to the choice of components, a partially hydrated acid-loaded carrier can still be suitable for the versatile applications of the present invention.

drying

After the salt exchange, i.e. the acid-base reaction forming the carrier salt structure, a possibly partially hydrated, acid-loaded carrier is obtained which is further processed by drying, grinding and sieving to a dried and comminuted, free-flowing powder of the invention in order to obtain a commercially salable, to obtain particulate, free-flowing product.

The drying according to the invention provides a pure, acid-loaded carrier compound according to the invention, since possible low-molecular by-products, eg water of condensation, have been removed. Since the boiling point of the by-products, in particular the water, and the charged acid(s) is different, controlled thermal purification of the compound according to the invention is advantageously facilitated. Proof of the successful drying of the compound according to the invention is possible, for example, by means of a thermogravimetric analysis (TGA).

As described above, drying in the process according to the invention is preferably carried out at temperatures 5° C.<T<15° C. below the boiling point of the components of the compound according to the invention in order to advantageously maintain the intended molar ratio of the compounds according to the ratio used. In this case it can be assumed that the ratio of the carrier carboxylic acid to the loaded carboxylic acid(s) is equal to the loading capacity of the compound according to the invention. According to the invention, slow evaporation of the laden acid(s) is avoided in the process of the invention by immediately cooling the acid-loaded carrier to room temperature, so that the desired molar ratio of the components of the compound according to the use ratio is advantageously retained.

The heat of reaction released during the exothermic reaction to form the carboxylic acid carrier, e.g. during the in situ neutralization, can be retained, e.g. by using insulated reaction vessels, and can be used advantageously for working up the compound according to the invention obtained, e.g. for drying. As a result, advantageously less time is required for drying the carboxylic acid salt carrier loaded with carboxylic acid than with a drying process at r.t.

The drying is typically carried out using suitable dryers selected from fluid bed dryers, vacuum dryers, spray dryers, paddle dryers or conventional vacuum drying systems. Since the compound of the present invention is selected from components having a low boiling point, having thermal degradability and having a low vapor pressure, mild conditions for purification and/or drying are preferred. Therefore, a preferred drying according to the invention is carried out in such a way that the loaded acid(s) does not escape from the final acid-loaded salt carrier product, e.g., by evaporation or desorption.

The preferred drying and grinding according to the method according to the invention yields a material with low water content, controlled particle size and/or bulk density.

granulation

Powdered carrier salts according to the invention loaded with C ₁ -C ₄ -carboxylic acid(s) are produced by grinding or crushing until a flowable, powdery mass is obtained. Subsequent screening makes it possible to separate out sizes above a desired size limit of the carrier salt. Both milling and screening are essential steps in sizing the compound of this invention to promote advantageously good flowability.

In addition to the advantages of free-flowing powders described above, the grinding produces a high relative surface area, which improves water release and thus supports the final drying of the powder according to the invention.

In this regard, dry-state granulation effectively reduces ongoing agglomeration and therein allows better control of final particle size. In addition, less mechanical energy is required to break up agglomerates into smaller particles, which advantageously reduces the total energy input during grinding. In a preferred embodiment of the invention, the starting materials in powder form are ground and dried at the same time. The conditioning preferably takes place simultaneously with the grinding process at an absolute humidity of at least 17 g water per kg dry air, preferably between 17 and 30 g water per kg dry air (cf. EP 0838529 B1 ). In this way, the agglomeration of many small individual particles to form larger spherical macrostructures of the powder according to the invention is effectively prevented.

Packaging

The loaded carboxylic acids are hygroscopic and therefore constantly absorb water. In a preferred embodiment of the invention, the dried and ground compound according to the invention is brought into a transportable form in the absence of moisture, preferably by filling into bottles or bags. The powdered compositions are preferably packaged in accordance with good manufacturing practice (GMP) as described in Title 21 Part 110 of the Code of Federal Regulations. Standard packaging such as sealed polyethylene (PE) containers or bags made from other materials, such as fiber-reinforced polypropylene with PE inner films or PE linings, are suitable for this.

In any case, the container should be sealed to avoid undesired moisture build-up of the products of the invention so that they retain their beneficial properties until use by the user. This step of the manufacturing process according to the invention takes account of the atmospheric relative humidity at room temperature in European latitudes, which is approximately >70%. By avoiding the ingress of moisture, the flowability of the acid-loaded carrier solids according to the invention is ensured.

use of the connection

The compound of the invention is applicable as an acidity regulator, as a buffering system, for preservation purposes or as a flavor in a wide range of pharmaceutical, cosmetic, food and feed industries where the compound improves shelf life, supports safety in the food chain, improves odor and/or increases palatability.

Embodiments, Examples and Realizations

The present invention is further described and illustrated in the following comparisons, experiments, drawings and examples which are not intended to limit the scope of the invention in any way.

character list

• 1 : the schematic representation of the ex-post process for preparing the carboxylic acid-loaded carboxylic acid salt carrier according to the invention from the components of the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-},$
  
  the charged carboxylic acid(s) R ² COOH, and the earth metal base consisting of M ²⁺ ;
• 2 : the schematic representation of the in situ process for preparing the carboxylic acid-loaded carboxylic acid salt carrier according to the invention from the components of the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-},$
  
  the charged carboxylic acid(s) R ² COOH, and the earth metal base consisting of M ²⁺ ;
• 3 : the particle diameter distribution curve in the cumulative volume (cum. volume) plot of the sample magnesium glutamate with loaded lactic acid MgGlu-HLac [2] in 4(A) , Calcium acetate with loaded acetic acid CaAc-HAc [2] in 4(B) and calcium tartrate with loaded acetic and propionic acid CaT-HAc-HProp[1,1] in 4(c) in each case against the particle diameter;
• 4(A) : the thermogravimetric analysis (TGA) curve of the dry sample MgFo-HProp [2] in the plot of weight loss as a function of temperature (at constant heating rate);
• 4(B) : the differential thermal analysis (DTA) graph of the dry sample MgFo-HProp [2], showing the caloric phenomena as a function of increasing temperature (at constant heating rate);
• 5(A) : the thermogravimetric analysis (TGA) curve of the partially hydrated sample CaAc-HAc [2], which was not dried after the synthesis. The weight loss is shown as a function of temperature (at a constant heating rate), with two second-order phase transitions of dehydration and desorption of the loaded carboxylic acid being recognizable;
• 5(B) : the differential thermal analysis (DTA) curve of the partially hydrated sample CaAc-HAc [2] which was not dried after the synthesis. The plot of the caloric phenomena as a function of temperature (at constant heating rate) reveals two distinct endothermic physicochemical phenomena, which are in agreement with the trends observed in the TGA analysis of CaAc-HAc [2];
• 6 : pH values of some representative compounds of the invention compared to the pH values of the corresponding isolated components thereof, namely the charged carboxylic acid(s) R ² COOH and the carrier carboxylic acids ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-},$
  
  forming a measurement pair along the vertical axis. Each of the 73 pairs is numbered 1 - 73, which refers to the corresponding number in Table 5. All measurements were made at 0.1 molar (M) concentration (c) of the samples carried out, which corresponds to 0.1 moles per liter (mol/L). The pH difference of the compounds according to the invention compared to the pH of the corresponding carrier carboxylic acid and/or the charged carboxylic acid(s) indicates the acid activity of the compounds according to the invention. For the listed values on which this figure is based, reference is made to Table 5;
• 7(A) : Volume comparison of French Style Bread (FSB) in liters, which demonstrates the applicability of the compound according to the invention for use as a preservative in baked goods (Example 12). The bread samples were dosed with the compounds of the invention as described on the x-axis;
• 7(B) : Comparison of the area cross-sections of the samples 7(A) and based on Example 12;
• 8th : Color development of a beef chuck steak blank sample (crosses) and a beef chuck steak sample calcium acetate with loaded acetic acid (CaAsc-Hac [2], diamonds) as a function of time as described in example 13. The colors of the RGB:R have been converted to black and white;
• 9(A) : total bacterial count of the samples described in example 14, which shows the usability of the compounds according to the invention as preservatives in meat products;
• 9(B) : Total yeast count of the samples described in Example 14, showing the utility of the compounds of the invention as preservatives in meat products;
• 10(A) : the results of the preservative efficacy test by total plate count (TBC, see Example 15);
• 10(B) : the results of the test to demonstrate the effectiveness of preservation by examining the total yeast/fungus count (see Example 15);
• 10(c) : the results of the test for detecting the preservative efficacy by examining the enterobacteria/β-glucuronidase-positive enterobacteria (E/β) number (see Example 15).

reference list

(T1.2)

tank

(PM1.1)

premixer

(M1.1)

mixer

(P1.1)

packing unit

(S1.1)

Sieve

(SM1.1)

sieve mill

(VS1.1)

vacuum drying plant

(C1.1)

Mill

List of abbreviations

Table 3 below lists examples of starting materials for the preferred embodiment of the compound according to the invention, together with their pK _a 's and some relevant boiling points (T _b , _acid ) for acidic forms which are preferably used as charged carboxylic acids. The abbreviations are used for the compound names as described in the nomenclature below.

Table 3. Abbreviations (first column) of the components used for the names of the preferred compounds of the invention, alongside the designations for the salt and acid forms of the components and the acid strength of the acid form of the components (pK _a1 ). shortcut salt mold acid form PC _a1 T _{b, acid} asp aspartate aspartic acid 1.99 glue glutamate glutamic acid 2:16 Times malonates malonic acid 2.83 T tartrate tartaric acid 2.98 salt salicylates salicylic acid 2.75 fum fumarate (trans) fumaric acid 3.00 cit citrates citric acid 3.09 mom malate malic acid 3.40 Fo format formic acid 3.77 101 Gly glycolate glycolic acid 3.83 75 Lac lactate lactic acid 3.86 122 asc ascorbate ascorbic acid 4.25 suc succinate succinic acid 4:19 ben benzoate benzoic acid 4.20 Ad adipate adipic acid 4.43 Ac acetate acetic acid 4.76 118 Bu butyrate butyric acid 4.82 163 Prop propionate propionic acid 4.88 141

Nomenclature:

von der/den beladenen, funktionellen Säure(n) (R²COOH) durch ein Minus (-) getrennt, wobei der beladene Träger immer vor der beladenen Carbonsäurekomponente genannt wird. Klammern [...] geben die molaren Äquivalente der beladenen Säure(n) bezogen auf das Trägersalz an und entsprechen n wie in den Ansprüchen beschrieben.Unless otherwise noted, is the name of the carrier salt ${\text{M}}^{}$${}^{2+}{\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

separated from the charged, functional acid(s) (R ² COOH) by a minus sign (-), with the charged carrier always being named before the charged carboxylic acid component. Brackets [...] indicate the molar equivalents of the charged acid(s) based on the carrier salt and correspond to n as described in the claims.

List of connection names

Table 4. Exemplary designations for some preferred compounds according to the invention, based on the abbreviations of the compounds given in Table 3, in addition to the explanations of the designations and the molar ratio of the loaded carboxylic acid to the carrier carboxylic acid salt carrier:loaded acid(s). name of the connection Explanations Carrier: loaded acid(s) MgFo-HAc [2] Magnesium formate with loaded acetic acid 1:2 MgFo HProp [2] Magnesium formate with loaded propionic acid 1:2 MgAsp-Sal [2] Magnesium aspartate loaded with salicylic acid 1:2 CaAsc-HAc [2] Calcium ascorbate with loaded acetic acid 1:2 CaAsc-HAc [3] Calcium ascorbate with loaded acetic acid 1:3 CaAsc-HProp [2] Calcium ascorbate with loaded propionic acid 1:2 MgGlu HLac [2] Magnesium glutamate loaded with lactic acid 1:2 CaAc-HAc [2] Calcium acetate with loaded acetic acid 1:2 CaSal-HLac [2] Calcium salicylate with loaded lactic acid 1:2 CaT-HAc-HProp [1,1] Calcium tartrate with loaded acetic acid and propionic acid 1:1:1 CaT-HAc [2] Calcium tartrate with loaded acetic acid 1:2 CaT-HLac [2] Calcium tartrate with loaded lactic acid 1:2 CaT-HProp [2] Calcium tartrate with loaded propionic acid 1:2 CaCit-HAc [2] Calcium citrate with loaded acetic acid 1:2 CaCit-HFo [2] Calcium citrate with loaded formic acid 1:2 CaGlu-HAc [4] Calcium glutamate with loaded acetic acid 1:4 CaCit-HAc [6] Calcium citrate with loaded acetic acid 1:6 CaCit-HAc [2] Calcium citrate with loaded acetic acid 1:2

Example 1 - The general ex post procedure

A typical process according to the preferred ex-post procedure is shown schematically in 1 shown.

In the ex-post process, the alkaline earth base, which is in tank T1.1, and the carrier carboxylic acid, which is in tank T1.2, are added to the reactor (R1) with gentle stirring. After the reaction has ended, the carrier carboxylic acid salt formed is pre-dried, e.g. using a vacuum drying system (VS1.1) with further mixing. The product (carrier salt) in the reactor (R1) is pre-screened (SM1.1) and fed into an intermediate tank T1.3.

The sieved carrier salt from tank T1.3 and the carboxylic acid to be charged from tank T1.4 are placed in a mixer (M1.1) with gentle mixing. Alternatively, an externally obtained carrier salt from tank T1.5 and the carboxylic acid to be charged from tank T1.4 are delivered to a mixer (M1.1) with gentle mixing. The resulting carboxylic acid-loaded carboxylic acid salt carrier product from the mixer (M1.1) is further dried while still being mixed, e.g. by transfer to the same vacuum drying system (VS1.1) used in the previous step. The dried product from M1.1 is then ground in a mill (C1.1) to ensure a sufficient particle size. After passing through a sieve (S1.1), the product is packaged in the packaging unit (P1.1).

als Ausgangsmaterial gekauft, um mit der Carbonsäure R²COOH beladen zu werden. Es hat sich z.B. gezeigt, dass zugekauftes wasserfreies Calciumcitrat geeignet ist, die erfindungsgemäße Salzträgerstruktur zu erzeugen, indem es mit Essigsäure zu Calciumcitrat mit beladener Essigsäure (CaCit-HAc) vermischt wird. In dieser Ausführungsform fehlt jedoch der wesentliche Charakter der Erfindung und zeigt daher nicht so optimale Ergebnisse wie das Ex-post-Verfahren und/oder das In-situ-Verfahren.In one embodiment of the preferred process of the invention, the carrier carboxylic acid ${\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

purchased as starting material to be loaded with the carboxylic acid R ² COOH. It has been shown, for example, that purchased anhydrous calcium citrate is suitable for producing the salt carrier structure according to the invention by mixing it with acetic acid to form calcium citrate with loaded acetic acid (CaCit-HAc). In this embodiment, however, the essential character of the invention is missing and therefore does not show such optimal results as the ex post method and/or the in situ method.

Example 2 - The general in situ method

A typical process according to the preferred in situ method is shown schematically in 2 shown.

In the in-situ process, the alkaline earth base is in tank T1.1. The ligand acid and the loaded/free acid are released from tank T1.2 and tank T1.3, respectively, to be premixed in vessel (PM1.1) until a homogeneous premix of the components is obtained. The acid premix from PM1.1 is delivered to the reactor (R1). The alkaline earth metal base from container T1.1 is then carefully added to R1 while stirring.

After the reaction has ended, the product obtained is dried, e.g. using a vacuum drying system (VS1.1). The drying is carried out in such a way that the loaded carboxylic acid is not released from the carboxylic acid-loaded carboxylic acid salt support, e.g. by evaporation. The resulting carboxylic acid salt carrier loaded with carboxylic acid is then ground using a mill (C1.1) in order to ensure a sufficient particle size. After passing through the sieve (S1.1), the product is packaged (P1.1).

Examples of compounds according to the invention which are successfully processed via the in situ method include various particularly preferred compounds according to the invention from a loaded carboxylic acid(s) and a carrier carboxylic acid salt, such as calcium citrate with loaded formic acid with the molar ratio n=2 (CaCit-HFo [ 2]), calcium tartrate with loaded lactic acid with n=2 (CaT-HLac [2]), magnesium aspartate with loaded salicylic acid with n=2 (MgAsp-Sal [2]), while higher acid loadings for example calcium glutamate with loaded acetic acid with n=4 (CaGlu-HAc [4]) or calcium citrate with loaded acetic acid with n=6 (CaCit-HAc [6]).

Example 3 - In situ synthesis MgFo-HAc

This example represents the laboratory synthesis of magnesium formate with loaded acetic acid, MgFo-HAc [2], via the preferred in situ method of the present invention.

Magnesium oxide (MgO) with a purity of >97% and a particle size of <0.03mm, glacial acetic acid (CH ₃ COOH) with a purity of 99-100% and formic acid (CH ₂ O ₂ ) with a purity of >96% is used.

The chemical equation describes the synthesis of MgFo-HAc [2]: MgO + 2CH ₃ COOH + 2CH ₂ O ₂ → Mg(HCO ₂ ) ₂ * 2CH ₃ COOH + ↑ H ₂ O

A solution of 41.55 g MgO, 120.10 g CH ₃ COOH and 95.90 g CH ₂ O ₂ was stirred for 30 minutes at room temperature (23°C) in a sealed 5dl thermo glass beaker.

A white paste was obtained and dried at 95°C for 45 min to obtain a white, solid, free-flowing and dust-free product.

PH measurements are useful to determine the acidity of the obtained carboxylic acid-loaded carboxylic acid salt carrier MgFo-HAc [2], which is characteristic of the loaded, physisorbed acetic acid. The acidic effectiveness of the loaded acetic acid within the magnesium formate support structure was verified by comparing the pH values obtained with the isolated magnesium formate as a reference material. The pH of MgFo-HAc [2] (pH 5.10 at 0.1 M and at r.t.) was significantly lower than the pH of the reference material magnesium formate (pH 7.90 at 0.1 M and at r.t.), suggesting that magnesium formate as Carboxylic acid salt carrier has been successfully generated by the process of the present invention and advantageously provides a repositioning function for excess free acetic acid.

Example 4 - In situ synthesis of CaT-HAc-HProp [1,1]

This example represents the laboratory synthesis of calcium tartrate with loaded acetic acid and propionic acid, CaT-HAc-HProp [1,1], via the preferred in situ method of the present invention.

Calcium hydroxide (Ca(OH) ₂ ) with a purity of >98% and a particle size of < 0 02mm, Glacial Acetic (CH ₃ COOH) with a purity of 99-100%, Tartaric Acid (C ₄ H ₆ O ₆ ) with a purity of >99% and Propionic Acid (C ₂ H ₅ COOH) with a purity of >99.5% were used.

The chemical equation describes the synthesis of CaT-HAc-HProp [1,1]: Ca(OH) ₂ + CH ₃ COOH + C ₂ H ₅ COOH + C ₄ H ₆ O ₆ → C ₄ H ₄ CaO ₆ * [CH ₃ COOH; _C2H5COOH ] ₊ ↑ _2H2O

For this purpose, 23.29 g Ca(OH) ₂ , 18.5 g CH ₃ COOH, 46.46 g C ₄ H ₆ O ₆ and 22.93 g C ₂ H ₅ COOH were placed in a closed 5 dl thermo glass beaker for 30 minutes at room temperature (23 °C). mixed. A white, hydrated paste was obtained and the water by-product was evaporated at 95°C for 5 min to obtain a grey, solid, free-flowing and dust-free product.

Evidence of the successful loading with propionic acid and acetic acid and the acidic activity of the compound according to the invention was provided by comparing CaT-HAc-HProp [1,1] with the acidity of isolated calcium tartrate. The pH of CaT-HAc-HProp[1,1] (pH 3.63 at 0.1 M and at r.t.) was significantly lower than the pH of the reference material calcium tartrate (pH 7.33 at 0.1 M and at r.t.), from which it is concluded that calcium tartrate loaded with acetic acid and propionic acid was successfully produced by the process of the invention, advantageously providing a storage function for excess free acetic acid.

Example 5 - Comparison between in situ methods and ex post methods

This example shows the comparison between the in situ method and the ex post method for generating calcium tartrate with acetic acid loaded with 2 molar equivalents of the loaded acid (CaT-HAc [2]) as an example of the compound of the invention.

In-situ method: This example shows the laboratory synthesis of a carboxylic acid-loaded carboxylic acid salt support CaT-HAc [2] using both the ex-post method of the invention and the in-situ method preferred according to the invention.

For the production of CaT-HAc [2], calcium hydroxide (Ca(OH) ₂ ) with a purity of >98% and a particle size of <0.02mm, glacial acetic acid (CH ₃ COOH) with a purity of 99-100% and Tartaric acid (C ₄ H ₆ O ₆ ) with a purity of >99% is used.

The following equation describes the synthesis of CaT-HAc [2]: Ca(OH) ₂ + 2CH ₃ COOH + C ₄ H ₆ O ₆ -> C ₄ H ₄ CaO ₆ * 2CH ₃ COOH + ↑ 2H ₂ O

For the in situ synthesis, 24.37 g Ca(OH) ₂ , 38.71 g CH ₃ COOH and 48.62 g C ₄ H ₆ O ₆ were mixed for 30 minutes at room temperature (23 °C) in a sealed 5 dl thermo glass beaker. to prevent the evaporation of reaction water and acid. The lower pK _a value of tartaric acid (C ₄ H ₆ O ₆ ) of 2.89 compared to the pK _a value of acetic acid of 4.76 allowed the simultaneous addition of all three substances with the formation of the C ₄ H ₄ CaO ₆ support structure stored free acetic acid was ensured.

A white hydrated paste was obtained and the aqueous by-product was evaporated at 95°C for 5 min to evaporate the aqueous by-product while avoiding the evaporation of the acetic acid. After drying, a white, solid, free-flowing and dust-free product was obtained.

To demonstrate that excess acetic acid was loaded into the calcium tartrate support structure and that the compound of the invention possesses the acidic properties expected for the compound of the invention, the pH of calcium tartrate acetic acid CaT-HAc [2] was compared with the pH of isolated compared to calcium tartrate.

As a result, the pH of CaT-HAc [2] (pH 3.56 at 0.1 M and at r.t.) was significantly lower than the pH of the reference material calcium tartrate (pH 7.33 at 0.1 M and at r.t.), suggesting that Calcium tartrate with loaded acetic acid has been successfully produced by the process of the invention, which advantageously provides a storage function for excess free acetic acid.

Ex post procedure: This example demonstrates the laboratory synthesis of a carboxylic acid loaded carboxylic acid salt support CaT-HAc [2] according to the preferred ex post procedure of the invention as opposed to the more preferred in situ procedure of the invention.

For the synthesis of CaT-HAc [2] according to the ex-post method, calcium hydroxide [Ca(OH) ₂ ] with a purity of >98% and a particle size of <0.02mm, glacial acetic acid (CH ₃ COOH) with a purity of 99-100% and tartaric acid (C ₄ H ₆ O ₆ ) with a purity of >99% are used.

The following chemical equations describe the synthesis of CaT-HAc[2] via an ex-post method as a two-step approach: Ca(OH) ₂ + C ₄ H ₆ O ₆ → C ₄ H ₄ CaO ₆ + 2H ₂ O _{C4H4CaO6 + 2H2O} + _{2CH3COOH → C4H4CaO6 2CH3COOH + ↑ 2H2O}

For the ex post synthesis of CaT-HAc [2], first CaT-HAc [2], 24.37 g Ca(OH) ₂ and 48.62 g C ₄ H ₆ O ₆ were smelted in a sealed 5 dl thermo glass beaker for 30 minutes stirred at room temperature (23°C). A white hydrated powder was obtained and then 38.71 g CH_3 COOH was added. The mixture of the three components was then stirred for 10 minutes at room temperature (23°C) in a sealed 5 dl thermos glass beaker.

A white hydrated paste was obtained and the water side product was evaporated at 95°C for 10 min to evaporate the water side product while avoiding evaporation of the acetic acid. After drying, a white, solid, free-flowing and dust-free product was obtained.

As a result, the pH of CaT-HAc [2] (pH 2.89 at 0.1 M and at r.t.) was significantly lower than the pH of the reference material calcium tartrate (pH 7.33 at 0.1 M and at r.t.), from which it is concluded that Calcium tartrate loaded with acetic acid has been successfully produced by the process of the invention, which advantageously represents a storage function for excess free acetic acid.

The compounds CaT-HAc [2], prepared according to the in situ and the ex post method, were compared. Both the in situ method and the ex post method allow the production of CaT-HAc [2] with a storage function for excess free acid. The pH of CaT-HAc [2] via the ex post methods (pH 2.89 at 0.1 M and at r.t.) and about the in situ methods (pH 3.56 at 0.1 M and at r.t.) are comparable. However, for reasons of economy, it can be concluded that the in situ method is preferable due to the significant reduction in both reaction and drying time.

Example 6 - Acid Holding Capacity of the Compound of the Invention

This example shows the acid holding capacity for very high carboxylic acid loadings (n=4), representatively demonstrated for calcium tartrate with acetic acid loaded with 4 molar equivalents of loaded acid (CaT-HAc [4]).

The person skilled in the art knows that when at least two starting materials are provided in the first step of the process according to the invention, the starting materials can be selected in stoichiometric or substoichiometric ratios to one another. To illustrate the acid capacity performance of a presented support, calcium tartrate loaded with 4 molar equivalent acetic acid, CaT-HAc [4], was synthesized by the in situ method of the invention and analyzed for the acid strengths of the compound of the invention.

For the synthesis of calcium tartrate with loaded acetic acid CaT-HAc [4], calcium hydroxide (Ca(OH) ₂ ) with a purity of >98% and a particle size of <0.02mm, glacial acetic acid (CH ₃ COOH) with a purity of 99 -100% and tartaric acid (C ₄ H ₆ O ₆ ) with a purity of >99%. The following chemical equation describes the synthesis of CaT-HAc [4]: Ca(OH) ₂ + 4CH ₃ COOH + C ₄ H ₆ O ₆ → C ₄ H ₄ CaO ₆ * 4CH ₃ COOH + ↑ 2H ₂ O

For the in situ procedure of CaT-HAc [4], 17.57 g Ca(OH) ₂ , 55.81 g CH ₃ COOH and 35.05 g C ₄ H ₆ O ₆ were placed in a sealed 5 dl thermo glass beaker at room temperature (23 ° C) Mixed for 30 minutes. A gray paste was obtained and dried at 95°C for 6 min to obtain a white, solid, free-flowing and dust-free product.

The pH value of CaT-HAc [4], pH 3.33 at 0.1 M and at rt.) was significantly lower than the pH value of the reference material calcium tartrate (pH 7.33 at 0.1 M and at rt.) and thus shows the high acid efficiency that is directly correlated with a very high loading capacity of the compound CaT-HAc [4] according to the invention. The successful generation of very highly loaded carboxylic acid(s) compounds via the most preferred in situ method of the invention is verified, which advantageously offers a high dose storage function for excess liquid acids.

Example 7 - Acidity of the compound of the invention

This example shows the acidity of several representative compounds of the invention, which is quantified via pH measurements.

A Seven2Go handheld pH meter S2 (pH measuring range: 2 to 20; resolution: 0.01) with an InLab Ultra Micro-ISM electrode (measuring range: pH 1 to pH 11; low-temperature membrane glass type; ceramic diaphragm; reference system with Ag+ ion trap from Argenthal) and with an in-lab routine pH electrode (measuring range: pH 0 to pH 14; ceramic diaphragm; reference system with Ag ⁺ ion trap from Argenthal) from Mettler -Toledo AG (Analytical, Switzerland) used.

unter vergleichbaren Bedingungen wie dem Lösungsmittel, der Konzentration, der Temperatur für alle Proben nachgewiesen.The acidity of several representative compounds according to the invention is determined by comparing the pH values of the compound according to the invention with the unstressed carboxylic acid R ² COOH or with the carrier carboxylic acid salt ${\text{M}}^{}$${}^{2+}{\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-},$

detected under comparable conditions such as solvent, concentration, temperature for all samples.

For reasons of comparability, compounds with the same loading ratio n=2, i.e. 2:1 of the loaded carboxylic acid to the carrier carboxylic acid, were selected for this analysis. Further examples for other loading ratios are listed in Table 5. The components used for this pH characterization were dry, solid, free-flowing and exhibited complete solubility as exhibited by the reference salts themselves. Analytes were dissolved in Millipore water, stirred for 5 minutes in a hermetically sealed vial, after which pH measurements at r.t. to perform. All measurements were performed at 0.1 molar (M) concentration of the samples, which corresponds to 0.1 mol per liter (mol/L).

For reasons of comparability, compounds with the same loading ratio n=2, i.e. 2:1 of the loaded carboxylic acid in relation to the carrier carboxylic acid, were selected for this analysis. Further examples for other loading ratios are listed in Table 5. The components used for this pH characterization were dry, solid, free-flowing and exhibited complete solubility as exhibited by the reference salts themselves. Analytes were dissolved in Millipore water, stirred for 5 minutes in a hermetically sealed vial, after which pH measurements at r.t. to perform. All measurements were performed at 0.1 molar (M) concentration of the samples, which corresponds to 0.1 mol per liter (mol/L).

For reasons of reliability, each result given is the average of at least three individual measurements. The following Table 5 summarizes the results of the pH analysis for the compound according to the invention (third line), the corresponding carrier carboxylic acid (fourth line) and the loaded carboxylic acid (fifth line), based on the corresponding abbreviations (second line) and numbers (first Line). The numbers 1-73 (number, first row) serve as assignment for the 73 pairs, consisting of the compound according to the invention (third row), the corresponding carrier carboxylic acid (fourth row) and the loaded carboxylic acid (fifth row), as in the 6 be used.

Table 5. Summarized experimental pH values of compounds according to the invention mentioned by way of example (third column), alongside their corresponding carrier carboxylic acid line by line (fourth column) and the loaded carboxylic acid (fifth column). The enumeration (no.) of the corresponding pairs is consistent with the 6 . No. abbreviation (connection) connection pH values carrier carboxylic acid loaded carboxylic acid 1 CaAc-HAc [2] 5.05 8.57 2.88 2 CaAc-HAc [3.5] 4.59 8.57 2.88 3 CaAc-HAc [3] 4.62 8.57 2.88 4 CaAc-HProp [2] 5.16 8.57 2.94 5 CaAsc-HAc [2] 4.42 8.28 2.88 6 CaAsc-HAc [3] 4.22 8.28 2.88 7 CaAsc-HAc [4] 4.22 8.28 2.88 8th CaAsc-HAc [5] 4.15 8.28 2.88 9 CaAsc-HAc [6] 4.12 8.28 2.88 10 CaAsc-HProp [2] 4.88 8.28 2.94 11 CaAsp-HAc [2] 4.42 8.15 2.88 12 CaAsp-HGly [2] 3.88 8.15 2.41 13 CaBen-HAc [2] 4.46 8.29 2.88 14 CaBen-HProp [2] 4.64 8.29 2.94 15 CaCit-HAc [2] 4.77 7.76 2.88 16 CaCit-HAc [5] 4.31 7.76 2.88 17 CaCit-HAc [6] 4.15 7.76 2.88 18 CaCit-HFo [2] 3.77 7.76 2.38 19 CaCit-HLac [2] 4.27 7.76 2.44 20 CaCit-HLac [4] 4.16 7.76 2.44 21 CaCit-HProp [2] 4.50 7.76 2.94 22 CaFo-HAc [2] 4.74 8.24 2.88 23 CaFo-HFo [2] 5.19 8.24 2.38 24 CaFo HProp [2] 5.79 8.24 2.94 25 CaFum-HAc [2] 4.17 8.11 2.88 26 CaFum-HFo [2] 3.58 8.11 2.38 27 CaFum-HLac [2] 3.68 8.11 2.44 28 CaFum HProp [2] 4.27 8.11 2.94 29 CaGlu-HAc [2] 4.52 7.24 2.88 30 CaGlu-HAc [4] 4.35 7.24 2.88 31 CaGlu-HLac [4] 3.60 7.24 2.44 32 CaGly-HProp [2] 4.63 7.24 2.94 33 CaLac-HAc [2] 4.58 8.28 2.88 34 CaLac-HLac [2] 3.45 8.28 2.44 35 CaLac-HLac [3] 3.38 8.28 2.44 36 CaLac-HLac [4] 3.30 8.28 2.44 37 CaMa-HAc [2] 4.53 7.45 2.88 38 CaM-HAc-HProp [1,1] 4.47 7.45 2.91 39 CaMa-HAc-HProp-HLac [1,1,1] 4.97 7.45 2.75 40 CaM-HProp [2] 4.45 7.45 2.94 41 CaSal-HLac [2] 3.43 7.59 2.44 42 CaSuc-HAc [2] 4.69 7.95 2.88 43 CaSuc-HProp [2] 5.01 7.95 2.94 44 CaT-HAc [2] 3.52 7.33 2.88 45 CaT-HAc [4] 3.33 7.33 2.88 46 CaT-HAc [5] 3.84 7.33 2.88 47 CaT-HAc-HProp [1,1] 3.63 7.33 2.91 48 CaT-HAc-HPro-HLac [1,1,1] 3.33 7.33 2.75 49 CaT-HLac [2] 3.27 7.33 2.44 50 CaT-HProp [2] 3.71 7.33 2.94 51 MgAc-HAc [2] 5.06 8.57 2.88 52 MgAc-HProp [2] 5.51 8.57 2.94 53 MgAsc-HAc [2] 4.34 8.28 2.88 54 MgAsp-Sal [2] 3.79 8.15 2.11 55 MgCit-HAc [2] 4.19 7.76 2.88 56 MgCit-HFo [2] 3.82 7.76 2.38 57 MgCit-HLac [2] 3.96 7.76 2.44 58 MgCit-HProp [2] 4.48 7.76 2.94 59 MgFo-HAc [2] 5.10 7.90 2.88 60 MgFo-HFo [2] 6.54 7.90 2.38 61 MgFo-HLac [2] 3.72 7.90 2.44 62 MgFo HProp [2] 4.84 7.90 2.94 63 MgFum-HAc [2] 4.13 8.11 2.88 64 MgFum-HFo [2] 3.76 8.11 2.38 65 MgFum-HLac [2] 3.69 8.11 2.44 66 MgFum HProp [2] 4.24 8.11 2.94 67 MgGlu HLac [2] 4.00 7.24 2.44 68 MgLac-HAc [2] 4.43 7.94 2.88 69 MgLac-HAc-H Prop [1,1] 4.48 7.94 2.63 70 MgLac-HLac [2] 3.31 7.94 2.44 71 MgLac-HProp [2] 4.45 7.94 2.94 72 MgSuc-HAc [2] 4.69 7.95 2.88 73 MgSuc-HProp [2] 5.18 7.95 2.94

The results from Table 5 are in 6 shown schematically, with the pH values of the compounds according to the invention being compared with the paring components along the vertical axis.

bzw. der entsprechenden unbelasteten Carbonsäure R²COOH weisen auf die saure Wirksamkeit der erfindungsgemäßen Verbindungen sowie die Stabilität der Trägerkomponenten hin.The significant differences in the pH values of the compounds according to the invention compared to the pH value of the corresponding carrier carboxylic acid salt ${\text{M}}^{}$${}^{2+}{\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

or the corresponding uncontaminated carboxylic acid R ² COOH indicate the acidic activity of the compounds according to the invention and the stability of the carrier components.

für alle Proben bestätigt, da sie pH-Werte im Bereich 7,2 < pH < 8,6 aufweisen (6, Kreuze). Diese fehlende saure Aktivität ist ein weiterer Beleg für die Vollständigkeit der Umsalzungsreaktion, also der Synthese nach dem erfindungsgemäßen Verfahren. Der Träger wirkt also vorteilhafterweise wie vorgesehen als nicht reaktive Trägerverbindung und ermöglicht die Einstellung der Acidität ausschließlich über die beladene Carbonsäure R²COOH.First, the stability of the carrier carboxylic acid salt ${\text{M}}^{}$${}^{2+}{\left({\text{<figure-callout id="1" label="R" filenames="DE102021115047A1\_0044.png,DE102021115047A1\_0047.png" state="{{state}}">R</figure-callout>}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

confirmed for all samples as they have pH values in the range 7.2 < pH < 8.6 ( 6 , crosses). This lack of acidic activity is further proof of the completeness of the resalting reaction, ie the synthesis according to the process according to the invention. The carrier thus advantageously acts as intended as a non-reactive carrier compound and enables the acidity to be adjusted exclusively via the charged carboxylic acid R ² COOH.

In contrast to the carrier carboxylic acid salt, the compounds according to the invention have a significant acidity (3.3<pH<6.5, rectangles), comparable to the acidity of the corresponding isolated carboxylic acid R ² COOH ( 6 , circles). This observation shows the acid strength of the physiosorbed carboxylic acid R ² COOH. The acid strength upon solvation of the compounds of the invention demonstrates the controlled acid release in solution, the compounds of the invention having been found to be advantageously stable to alternative release eg by thermal desorption of the loaded acids (the reader is referred to Examples 8 and 9).

As a representative example of a highly loaded compound according to the invention, calcium tartrate with loaded lactic acid CaT-HLac [2] showed a pH value of 3.27 (c=0.1 M), which is well below the pH value of calcium tartrate with pH 7.33 (c=0.1 M). and thus clearly shows the repository function even for a molar excess of loaded free acetic acid (n=2), which further confirms the technical suitability of the method according to the invention.

However, all solutions containing the compound according to the invention in water are characterized by a distinctly acidic pH, compared with the neutral to slightly alkaline character of the unloaded corresponding carrier carbon salts.

Example 8 - Thermal Analysis of a Dry Joint

This example demonstrates the thermal analysis consisting of thermogravimetry (TGA) and differential thermal analysis (DTA) for a representative compound of the invention MgFo-HProp [2] in the dry state, information on the release of the loaded acid(s) and the stability of the support structure are.

Thermal analysis was performed with a Linseis STA 1600 Simultaneous Thermal Analyzer to determine simultaneous weight changes (TGA signal) and calorically measurable conversions (DTA signal) over a temperature range between r.t. and 300°C. The compound according to the invention (100 mg) was placed on a sample holder of the measuring device and heated to 300° C. in a gas flow of 50 ml/min of nitrogen at a heating rate of 2 Kelvin per minute.

The results of the thermal characterization of the sample MgFo-HProp [2] in the dry state are in 4 shown.

the 4(A) shows the curve of the change in weight as a function of increasing temperature at a constant heating rate obtained from the thermogravimetric analysis (TGA) of the dried sample MgFo-HProp [2]. A single second-order phase transition is obtained around the inflection point T _x . The sample MgFo-HProp [2] shows a total weight loss of 2.4 wt% when heated in the range of 125°C to 200°C. The weight loss correlates with the desorption of the _physiosorbed carboxylic acid since the temperature of the weight loss around Tx coincides with the boiling point of the loaded propionic acid (bp _Tb = 141).

On the one hand, the anhydrous character of the sample is proven, since no further weight change is observed, especially not in the range of the boiling point of water (100° C.), which confirms the efficiency of the drying step in the course of the production process according to the invention. On the other hand, the thermal stability of the carrier carboxylic acid salt MgFo-HProp [2] in a temperature range r.t. and 300°C, since no further weight loss is observed at accelerated temperatures in the range of 200°C >T> 300°C.

The position of the turning point T _x gives an indication of the strength of the physisorption of the inclusion compound according to the invention, since more energy is required for the evaporation of the loaded propionic acid compared to the evaporation of propionic acid (T _s = 141° C.), which increases the stability of the compound according to the invention approved.

Furthermore, the flat shape of the weight loss curve around the Tx in the range 125° _C to 200°C indicates a smooth release of the loaded carboxylic acid compound, indicating the desired control of the acid release. Such a controlled release advantageously prevents undesired “burst release” of the loaded carboxylic acid. The weight loss, if it is only due to the desorption of the loaded acid, can advantageously be used for quantitative information about the loading capacity of the compound according to the invention.

In 4(B) the DTA signal of the differential thermal analysis (DTA) of the dried sample MgFo-HProp [2] is shown, showing the caloric phenomena as a function of increasing temperature (at constant heating rate). A single significant caloric change of the sample MgFo-HProp [2] is observed between 125°C and 200°C. Consistent with the temperature range of greatest weight loss recorded by the TGA signal, the DTA signal shows an endothermic reaction in this temperature range, indicating desorption of the physiosorbed loaded carboxylic acid from the carboxyl carrier inclusion. The position of the absolute minimum T _x gives indications of the strength of the physisorption of the inclusion compound according to the invention, since more energy is required for the evaporation of the loaded propionic acid than for the evaporation of propionic acid (T _s = 141° C.), which increases the stability of the compound according to the invention approved.

The meeting of TGA and DTA curves in 4 demonstrates semi-quantitatively the release of propionic acid and the purity of the product according to the invention as well as the thermal stability of the carrier carboxylic acid salt MgFo-HProp [2] up to 300°C.

Example 9 - Thermal analysis before drying

This example shows the thermal analysis consisting of thermogravimetry (TGA) and differential thermal analysis (DTA) for CaAc-HAc [2] before the drying step according to the method of the invention, the information about the water content before drying, the efficiency of the thermal cleaning during drying, the release of the loaded acid and the stability of the support structure.

The thermal analysis was carried out according to Example 8.

the 5(A) shows the course of the thermogravimetric analysis (TGA) of the partially hydrated sample CaAc-HAc [2] before drying in the course of the method according to the invention and represents the weight loss as a function of increasing temperature at a constant heating rate. The result curve shows two distinct stages of weight loss. The first significant weight loss (-7.0 wt% of total weight) takes place between 25-135°C and the second stage of weight loss (11.7 wt% of total weight) can be observed in a range of 135-300°C . The total weight loss of the partially hydrated sample CaAc-HAc [2] at a constant heating rate between rt and 300°C is 18.74%.

Two distinct second-order phase transitions indicate the expected physical phenomena of evaporation of the side product water during drying and desorption of the loaded carboxylic acid. The evaporation of the water is indicated by the first inflection point _T1 of the TGA curve, since it coincides with the boiling point of water (100°C), while the desorption of the loaded carboxylic acid is related to the second inflection point of the TGA curve _Tx , since T _x can be related to the boiling point of the loaded acetic acid (118°C).

The evaporation of the water takes place around T ₁ and is completed at a significantly lower temperature than in the temperature range in which the evaporation of the loaded acetic acid takes place (around T _x ). These exemplary results of the representative sample of the compound according to the invention, CaAc-HAc [2], for the TGA analysis thus show the successful drying of the compound according to the invention.

Even if the TGA analysis does not provide absolute qualitative information, information about the material released is possible by referring to the caloric information of the DTA curves, as in 5(B) shown.

the 5(B) shows the course of the differential thermal analysis (DTA) of the partially hydrated sample CaAc-HAc [2] before drying in the course of the method according to the invention and demonstrates the caloric phenomena as a function of the increasing temperature at a constant heating rate. The DTA signals show two different endothermic physicochemical phenomena by two minima of the DTA signal confirming the drying of the sample from the water (T ₁ ) and the desorption of the physiosorbed loaded carboxylic acid from the carboxyl carrier inclusion (T _x ).

However, the position of the absolute minimum T _x gives indications of the strength of the physisorption of the inclusion compound according to the invention, since more energy is required for the evaporation of the loaded acetic acid compared to the evaporation of acetic acid (boiling point T _b = 118 ° C), which the stability of the compound of the invention confirmed. The comparatively increased thermal energy required to liberate the loaded carboxylic acid from the support structure indicates a superposition of the energy required for vaporization, which is generally required for the isolated carboxylic acid, and the energy required to overcome the attractive forces of physisorption of the loaded carboxylic acid on the inclusion compound of the invention.

Since no further changes in the TGA and DTA signals are observed, the purity of the compound according to the invention with regard to low-molecular impurities is proven. Furthermore, the thermal stability of the support carboxylic acid salt sample CaAc-HAc [2] in a temperature range between r.t. and 300°C validated.

Drying by the process according to the invention advantageously enables the thermal purification of the carboxylic acid salt carrier laden with carboxylic acid from the main side product water, since the boiling point of and of the laden acid(s) differs from the boiling point of the side product.

Example 10 - Particle Size and Particle Size Distributions

This example demonstrates the powder quality, e.g., flowability and non-aerosol properties, of representative compounds of the invention as detected by diffraction granulometry.

The powder particle size and size distributions were determined using a Cilas 920 laser diffraction granulometer from Quantachrome (wavelength of the incident laser beam: 830 nm), which measures particle size distributions in the size range from 0.2 to 500 μm of wet dispersions or dry powders. All optical components are rigidly mounted on a cast-iron base plate, keeping the analyzer always level, sample circulation was achieved by two peristaltic pumps. The data analysis of the recorded diffraction patterns was carried out on the basis of the Fraunhofer-Mie diffraction theories.

The results of the representative samples are represented by the distribution curves in 3 are reproduced in which the cumulative volume (cumulative volume) is plotted against the particle diameter. The distribution curve of the magnesium glutamate sample loaded with lactic acid MgGlu-HLac [2] is in 4(A) shown, while the results of calcium acetate with loaded acetic acid CaAc-HAc [2] in 4(B) and the results of calcium tartrate with loaded acetic and propionic acid CaT-HAc-HProp [1,1] in 4(c) are shown.

Analysis of the shape of the distribution curves allows evaluation of the mean particle diameters (d _av , d ₅₀ , d ₉₀ as introduced above). The characteristic mean particle diameters (d _av d ₅₀ , d ₉₀ ) of the particle size distribution are given in Table 6 below.

Table 6. The characteristic mean particle diameters (d _av d ₅₀ d ₉₀ ) of exemplary compounds according to the invention based on the analysis of the particle size distribution curve in FIG 4 . name of the connection dav / _µm d ₅₀ / µm d ₉₀ / µm MgGlu HLac [2] 99 68 233 CaAc-HAc [2] 221 208 400 CaT-HAc-HProp [1,1] 220 209 400

The particle size distributions of the samples CaAc-HAc [2] and CaT-HAc-HProp [1,1] show comparable average particle diameters d _av of about 220 μm, which is in the preferred particle size range according to the invention and advantageously supports flowability.

Furthermore, the shape of the distribution curves of the samples CaAc-HAc [2] and CaT-HAc-HProp [1,1] (see 4(B) and 4(c) ) similar, indicating that the method of the invention is applicable to a variety of samples with potentially different granulation properties. The mean particle diameters (d ₅₀ , d ₉₀ ) confirm the uniform or homogeneous character of the particle sizes of CaAc-HAc [2] and CaT-HAc-HProp [1,1]. The size distribution curves of these representative samples show the suitability of the compound according to the invention for any powder-processing manufacturing process, for example for weight-accurate filling, gravity dosing and uniform and precise powder dosing on a commercial scale.

In contrast, the in 4(A) shown sample MgGlu-HLac [2] smaller particles with an average particle size d _av of about 99 µm (see Table 6). The broader distribution of the sample MgGlu-HLac[2] is due to the flattened shape of the distribution curve of 4(A) and the difference in the mean particle diameters d _av and d ₅₀ can be seen. Even if the unit of the particle size distribution and the particle size for the sample MgGlu-HLac [2] is smaller than for the samples CaAc-HAc [2] and CaT-HAc-HProp [1,1], no aerosol properties are advantageously recognizable. Due to the preferred size ranges applicable to the compound according to the invention, no inhalation via the lungs or harmful respiration of the particles is to be expected. Therefore, contact with living beings during processing and Handling must not be strictly avoided, which is advantageous in terms of safe handling.

Example 11 - Use as a preservative in baked goods

This example demonstrates the applicability of the compound of the invention for use as a preservative in baked goods.

A variety of compounds of the invention have been used as a preservative for test baked goods, French Style Bread (FSB) and Mexican Style Tortilla (MST). The compounds used in this test were chosen because they are approved as GRAS food additives in relation to the FDA and EFSA (Food Additives Database and Substances Added to Food Database, 2021) and are therefore suitable for application to baked goods.

The preparation of the French-style bread was carried out according to the ingredients in Table 7. The baking process was carried out using the Princess Breadmaker 152006 (setting: P1; 1.5 lb loaf size; medium colour) with a total baking time of 2:53 hours. The bread was then cooled down to 21°C and cut into 20 mm thick slices.

All of the ingredients were mixed into a dough and flat, tortilla-shaped samples were formed. All samples were baked on a hotplate at approximately 300°C for a total of 3 minutes per side. The tortilla samples were then cooled to 21°C.

Table 7. French Style Bread (FSB) and Mexican Style Tortilla (MST) Recipes. ingredients FSB / g MST/g flour 350 320.0 water 190 6.0 rapeseed oil 15 2.0 sugar 15 63.8 Salt 5 237.0 dry yeast 7 320.0

The samples were exposed to the compounds of the invention according to the dosage or flour weight indicated in Table 7, with the exception of the blank samples without exposure to the compound of the invention. The individual samples were then sealed airtight in a polyethylene zip-lock bag and stored under comparable conditions (red, in the dark) for 30 days. It is well known that defining the shelf life of a food is a difficult task and is an area of intense research for food product development scientists including food technologists, microbiologists, packaging experts such as Gabric and more, therefore preservative effectiveness was established through visual and olfactory detection of initial mold infestation . The results of the preservation test are summarized in Table 8.

Table 8. Results on the preservability of additives in bakery products preservation / days additives dosing objects <7 7-14 15-21 22-30 >30 none (blank) - MST x CaAc-HProp [2] 0.3% MST x none (blank) - FSB x CaAc-HProp [2] 0.2% FSB x CaAc-HAc [2] 0.3% FSB x CaT-HAc [3] 0.3% FSB x

The chemical kinetic principles of the compound of the invention allow for a significant increase in preservation of at least 7 days for all samples without loss of food quality. An increase of 0.2% by weight of the compound of the invention is effective to increase the preservation time up to 30 days. Increased shelf life upon exposure to even low doses of the compound of the invention opens avenue for new food packaging. The preservative properties of the compound of the present invention surpass conventional preservatives in comparable industries due to their low cost and health benefits. In particular for products intended for immediate consumption, such as fresh baked goods, where packaging requirements are often minimal, the compound of the present invention effectively prevents food degradation.

Example 12 - Use for increasing volume and conditioning dough in baked goods The following experiments demonstrate the bread-improving and dough-conditioning effect of several exemplary compounds according to the invention. French Style Bread (FSB) was used as the test object.

All ingredients were dosed so that each sample contained 200 ppm ascorbate, typically used as the active ingredient in industry standard bread improvers. One sample was exposed to no additive (Blank), one reference was exposed to ascorbic acid (200 ppm) and another reference was exposed to calcium ascorbate (220 ppm), and two samples were exposed to compounds of the invention containing calcium ascorbate with loaded acetic acid (CaAsc-HAc [2] , 280 ppm) and calcium ascorbate with loaded acetic acid (CaAsc-HProp [2], 300 ppm).

The volume-enhancing effect was determined by volumetric measurements. The results of the tests carried out are in the 7(A) to find and show that the additives lead to an increase in volume of the bread compared to the blank sample. The volume-increasing effect of the compounds according to the invention exceeds the bread improver additive customary in the industry at the same dosage of the active ingredient ascorbic acid and/or ascorbate, which demonstrates the suitability of the compound according to the invention as a volume-increasing additive for doughs of baked goods. 7(B) shows the cross-section of various samples, which advantageously have a uniform volume expansion in accordance with the optical requirements in the bakery industry.

Example 13 - Use for color retention in meat products

The following experiments outline the color retention function of the compound according to the invention for the exemplary sample calcium ascorbate with loaded acetic acid (CaAsc-HAc [2]). Samples of grass-fed, grass-finished beef chuck steak were used as test objects. All tests were carried out under the same conditions at 20°C. The compound CaAsc-HAc [2] according to the invention meets the requirements for GRAS food additives with regard to the regulations of the FDA and EFSA. The additive was dosed at 0.2% by weight and applied to the surface of the sample.

The effectiveness of color preservation was determined using the method of k-means clustering and an ex-post analysis of the mean RGB:R shift. The colors give an indication of the state of the myoglobin in the meat, whether it is deoxygenated, oxygenated, methionated or in the carboxy-myoglobin state. the 8th shows a clear color change for the blank sample (dashed line) compared to the sample treated with CaAsc-HAc [2] (solid line).

The method of k-means clustering and the ex-post analysis of the mean RGB:R shift gave a more quantitative view of the aforementioned color shift. The course of the color change over time already shows a significant difference for the blank sample compared to the sample treated with CaAsc-HAc [2] after 24 hours, as in 8(B) shown.

This indicates that the blank loses its characteristic red color earlier than the treated sample over the 72 hour time frame (see Fig 8(B) ). From this it can be concluded that CaAsc-HAc [2] enables effective color retention of meat products.

Example 14 - Use as a preservative in meat products

In the following series of tests, the preservation functions of calcium ascorbate with loaded acetic acid (CaAsc-HAc [2]) are shown as representative of the compounds according to the invention. Samples of grass-fed, grass-finished beef chuck steak were used as test objects. All tests were carried out under the same conditions. The compound CaAsc-HAc [2] according to the invention meets the requirements for GRAS food additives with regard to the regulations of the FDA and EFSA. The additive was dosed at 0.2% by weight and applied topically to the sample. The tests were carried out at 4°C and 20°C. The effectiveness of the preservation was determined by testing for total plate count and yeast/fungus count. The test for the total plate count (see 9(A) ) shows that the treated samples showed less bacterial contamination compared to their blank experiments at both 4°C and 20°C. The yeast count test (see 9(B) ) shows that the treated samples perform slightly better than their blank counterparts.

The use of the compound according to the invention enables an effective reduction in the total number of germs and in yeast formation in the first 164 hours after incubation. The compound CaAsc-HAc [2] according to the invention can therefore be used advantageously as a preservative in meat products.

Example 15 - Use as a preservative in silage

In the following test series, the silage preservation functions of calcium formate with loaded formic acid (CaFo-HFo [2]), calcium formate with loaded propionic acid (CaFo-HProp [2]) are shown as representatives of the compounds according to the invention. Feed samples consisting of approx. 90% pasture grass and 10% green rye with a DM content of 30.75% were used as test objects. All tests were carried out under the same conditions. The compounds CaFo-HProp [2] and CaFo-HFo [2] according to the invention meet the requirements for GRAS food additives based on the regulations of the FDA and EFSA. The additives were dosed at 0.5% by weight and applied topically to the samples. The tests were conducted under rt in a time frame of 31 days. Preservation effectiveness was determined by examining total bacterial count (TBC), yeast/fungus count and enterobacteria/β-glucuronidase-positive enterobacteria (E/β). The test results show that both CaFo-HProp [2] and CaFo-HFo [2] at a dosage of 0.5 wt% were able to reduce the TBC (see 10(A) ), the yeast number (see 10(B) ) and the E/β number (see 10(c) ) to be drastically reduced.

In particular, CaFo-HProp [2] was able to completely inhibit the growth of yeasts and β-glucuronidase-positive enterobacteria (especially E. coli), which are particularly undesirable in silage fermentation ( 10 ).

From this it can be concluded that the compounds according to the invention are able to reduce the total bacterial count, the formation of yeast and the formation of enterobacteria better than the blind test in the first 744 hours after incubation.

Example 16 - Use for cosmetic applications

This example demonstrates the use of the compound according to the invention for cosmetic applications, shown here as an additive for a shaving soap.

Liquid shaving soaps containing no additives (blank) were prepared, using 1% by weight of malic acid, 1% by weight of calcium citrate, 2% by weight of calcium salicylate with loaded lactic acid (CaSal-HLac [2]) and 1% by weight of -% calcium citrate with loaded acetic acid (CaCit-HAc [2]) were added. An overview of the samples can be found in Table 9.

Table 9. Samples and results of application in shaving soap. no . additives wt% thickening Stability (> 24h) 1 Blank 0 - no 2 malic acid 1 + no 3 calcium citrate 1 - Yes 4 CaSal-HLac [2] 2 ++ Yes 5 CaCit-HAc [2] 1 +++ Yes

Each sample of Aleppo-style Arabic soap, consisting of 16% sodium hydroxide, 71.4% olive oil and 12.6% laurel oil, was cut into 22 g sample sizes and placed in a bowl to which 22g of water was added. The mixture was stirred with undissolved pieces of hard soap and placed in a microwave oven at 600 W for 50 seconds. Thereafter, the respective additives were added in the aforementioned dosage with 44 g of water, which led to the dissolution of the remaining pieces of hard soap. In addition, a change in color and consistency could be observed as the mixture turned into a white and creamy substance. The mixture was placed in a microwave at 600 W for 80 seconds. Thereafter, the resulting mixture was mixed by hand and poured into a jar for testing and storage. Table 9 shows the thickening and stability results.

All in all, the mix of the acid-loaded carrier substances with the hard aleppo-style arabic soap and water yielded a thick-foamy, yet liquid soap which turned out to be stable. This results in a product suitable as a shaving soap as the flow properties display a gliding effect when shaving, enabling a smoother and closer shave whilst employing acids with the potential to clean out the skin's troubles whilst simultaneously disinfecting razor burns.

Overall, the mixture of the acid-loaded vehicles with the Aleppo-style hard Arabic soap and water yielded a thick-lathering but liquid soap that was found to be stable. This results in a product that is suitable as a shaving soap as the flow properties provide a lubricating effect when shaving allowing for a smoother and closer shave whilst the acids have the potential to rid the skin of impurities whilst disinfecting razor burn.

QUOTES INCLUDED IN DESCRIPTION

This list of the documents cited by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Patent Literature Cited

• US20080317921A1 [0006]
• WO 9707687 [0008]
• EP 1761133 B1 [0008]
• US3672914A [0011]
• US4703014 [0105]
• EP 0838529 B1 [0116]

Claims (18)

A solid compound prepared as a powder having good flowability comprising the following structure, $${\text{M}}^{2+}{\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}\cdot {\text{No}}^2\text{COOH}$$

a carboxylic acid carrier salt ${\text{M}}^{2+}{\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

where M ²⁺ is an alkaline earth metal ion, preferably calcium (Ca), magnesium (Mg), barium (Ba) or a divalent metal ion selected from iron (Fe), copper (Cu), zinc (Zn), manganese (Mn), tin (Sn) or a mixture thereof, R ¹ is an optionally substituted C ₁ -C ₁₀ alkyl group or an optionally substituted aryl group, the substituents being selected from a carbonyl group (=O), an amino group (NH ₂ ), a hydroxy group (OH), a halogen, a cyano group (CN) or a mixture thereof, and where m is 0 to 2, a charged carboxylic acid R ² COOH, where R ² is an optionally substituted C ₁ -C ₁₀ alkyl group, the substituents are selected from carbonyl group (=O), amino group (NH ₂ ), hydroxy group (OH), halogen or cyano group (CN) or a mixture thereof, where 1 < n ≤ 6; characterized in that the pK _a1 of the corresponding carboxylic acid of the carrier carboxylic acid ${\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

≤ pK _a1 of the loaded carboxylic acid(s) R ² COOH, the loaded carboxylic acid(s) R ² COOH within the structure of the carrier carboxylic acid salt ${\text{M}}^{2+}{\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

is (are) physisorbed. Solid connection to claim 1 , where R ² COOH is a short chain carboxylic acid or a mixture of formic, acetic, glycolic, propionic, lactic and/or butyric acid(s). Solid connection to claim 1 or 2 , where M ²⁺ is calcium (Ca) or magnesium (Mg). Fixed connection according to one of the preceding claims, wherein ${\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

formate, acetate, glycolate, propionate, lactate, butyrate, succinate, fumarate or maleicate, adipate, malate, malonate, citrate, tartrate, aspartate, glutamate, benzoate, salicylate or ascorbate. A solid compound according to any one of the preceding claims, wherein the mean particle diameter is in the range of 50 to 250 µm. A solid composition according to any one of the preceding claims, wherein the composition comprises less than 10.0% by weight water. Process for preparing the compound according to any one of Claims 1 until 5 , wherein the support structure is obtained by a) premixing the ${\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

and the R ² COOH carboxylic acids, b) adding an alkaline earth metal base comprising the M ²⁺ cation to step (a), c) stirring the mixture from step (b) below the boiling point of the most volatile acid present, d) drying the in step (c) mixture obtained. Process for preparing the compound according to any one of Claims 1 until 5 , wherein the support structure is obtained by a) premixing the alkaline earth metal base containing the M ²⁺ cation with the ${\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

Acid, b) stirring the mixture from step (a) below the boiling point of the acid present, c) drying the mixture obtained in step (b), d) adding the R ² COOH acids to the ${\text{M}}^{2+}{\left({\text{R}}^1\text{COO}\right)}_{2-\text{m}}^{\left(\text{m+1}\right)-}$

salt from step (c), e) stirring the mixture from step (d) below the boiling point of the most volatile acid present, f) drying the mixture obtained in step (e). Method of making the connection claim 6 or 7 , wherein the compound is stirred at temperatures below the boiling point of all components for less than 50 minutes. Method of making the connection claim 6 or claim 7 wherein the by-product is removed, the compound being dried and containing less than 10.0% by weight of the by-product. Method of making the connection claim 6 or claim 7 , wherein the reaction mixture is cooled to a temperature below 60°C in order to package the final product without further purification. Using a connection according to any of the Claims 1 until 10 for acidity control and/or as a buffering agent in cosmetic, pharmaceutical, food and feed applications. Using a connection according to any of the Claims 1 until 10 as an antimicrobial preservative in cosmetic, pharmaceutical, food and feed applications. Using a connection according to any of the Claims 1 until 10 as flavoring and flavoring agents in pharmaceutical, food and feed applications. Using a connection according to any of the Claims 1 until 10 as a color retention agent in food and feed applications. Using a connection according to any of the Claims 1 until 10 as a zootechnical additive in animal nutrition, such as a gastrointestinal acidifier or non-antibiotic growth promoter. Using a connection according to any of the Claims 1 until 10 as a dietary supplement in the dietary supplement for humans and animals. Using a connection according to any of the Claims 1 until 10 as an active ingredient in cosmetic and pharmaceutical applications.

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