WO2011070553A1

WO2011070553A1 - Procedure for obtaining coated acid salts

Info

Publication number: WO2011070553A1
Application number: PCT/IB2010/055773
Authority: WO
Inventors: José María LINARES VIDAL; Pere Parres Pallares
Original assignee: Avicola De Tarragona, S.A.
Priority date: 2009-12-10
Filing date: 2010-12-13
Publication date: 2011-06-16
Also published as: WO2011070553A8; ES2361759B2; ES2361759A1

Abstract

A procedure is described for obtaining a partially or totally coated acid salt comprising realising an exothermic reaction between at least one acid and least one base in the presence of at least one protective substance. Subsequently, the mass is allowed to cool and converts into a dry, fluid powder wherein the product is partially or totally enterically coated. The protective substance is a hydrogenated fat, a derivative of cellulose, a polysaccharide, an acrylate derivative or any other substance capable of forming a protective film. To the reaction there may be added one or several further products to be protected, these binding with the acid salt formed by the exothermic reaction.

Description

PROCEDURE FOR OBTAINING COATED ACID SALTS

FIELD OF THE INVENTION

The present invention is related to the techniques employed in the isolation and protection of substances and compounds by coatings, and more particularly, it is related to a process for obtaining acid salts coated by an exothermic reaction between at least one acid and at least less a base in the presence of at least one protective substance, where at the end of the reaction an acid salt coated by the protective substance is obtained. Optionally, in the reaction, at least one additional substance to be protected can be included, such as an active ingredient or a trace element that is also coated and can be attached to the acid salt. The procedure allows to obtain particles coated with a nanometric size, where the coating can be enteric, partial or total

BACKGROUND OF THE INVENTION

The use of protected products, whether microencapsulated, coated, etc. It is widely used and aims to isolate a product from abroad, for example, in the case of pharmacological active ingredients, it is sought to isolate said product to avoid physical contact with other substances or to provide the protected product with an exclusive action to bowel level and overcome its transit through the stomach without any loss or interference. In other words, it can be mentioned that the current way of protecting or microencapsular is based on the fact that the protective substance traps and isolates the active substance in its entire outer surface as a coating. Likewise, using traditional techniques, a particle size below 100 nanometers is not reached.

In order for the protected or microencapsulated product to overcome the stomach and dissolve in the intestine, the product must be provided with a protective layer so that, once the desired point of intestinal transit reaches, it releases the active substance. This is achieved with pH-sensitive protective substances or with hydrogenated fats, the latter having a melting point higher than the body temperature of the animals, thus maintaining a solid form, so that, upon reaching the intestine, said hydrogenated fats are dissolved for the lipases (enzymes that act against fats), releasing the active ingredient from the coating.

In essence, the current processes for obtaining coatings include heating, until it becomes a liquid, a fat that is maintained in that state in a hot container, where it is conducted to a heated mixer, where the hot fat is atomized on an acid salt Whether in an atomization tower, a mixer or other equipment that forms a fluid bed, however, this traditional technique has the following disadvantages: a significant energy expenditure is required to heat and maintain a fat temperature. Likewise, a large amount of grease is necessary to achieve an effective coating, however, the coating obtained by this traditional technique is usually fragile.

Finally, it is important to point out that the traditional coating or microencapsulation formation is carried out as the final (finishing) phase of the product's elaboration, that is, previous steps are necessary to reach the final product.

Therefore, new procedures are needed to obtain coatings for the protection of active ingredients, where less energy is used, eventually shorter manufacturing times and which basically allow for an effective coating. Likewise, new coatings are needed that allow the incorporation of active ingredients that can be considered with nanometric size, that is, particles smaller than 100 nanometers.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a new form of protection where less energy is used and the coating is more homogeneous, complete and effective on an acid salt. For this, the process of the present invention comprises reacting at least one acid, either organic or inorganic, with at least one base, in the presence of at least one protective substance, which is selected from a hydrogenated fat, a derivative of cellulose, polysaccharides, acrylate derivatives and in general substances capable of forming a protective film. In the reaction, an acid salt coated by the protective substance is obtained. The protective substance is distributed with the acid salt forming a homogeneous mass. Subsequently, at the end of the reaction, the homogeneous mass is allowed to cool which, as the temperature drops, becomes a fine powder where the acid salt is coated. The powder is dry and fluid, because at the end of the reaction phase, any substance capable of evaporating has been released. One of the advantages of the present invention is that the coated acid salt can have nanometric particle size.

In an alternative embodiment of the invention, in the reaction, at least one additional substance to be protected may be present that binds to the acid salt to be both coated.

In a further embodiment of the invention, in the reaction, water is added to cause the exothermic reaction, for example, by adding malic acid, the presentation of this is solid powder, and the corresponding base for manufacturing eg calcium malate , would be calcium hydroxide, also powdered. To make the acid and base react in this case, the use of water is needed. In yet another embodiment, the acid, water and base are added simultaneously once the remaining ingredients have been mixed.

When the protective substance is a hydrogenated fat, the exothermic reaction is used in the formation of the acid salt as a source of heat to melt and homogeneously distribute the hydrogenated fat over the acid salt. In this embodiment, it has been unexpectedly observed that particle sizes of less than 100 nanometers are obtained, whether the coated acid salt is formed or the acid salt is formed with the additional substance. In this case a partial or total coating can be achieved.

Where appropriate, when the protective substance is a cellulose derivative, a polysaccharide, acrylate derivatives and / or in general substances capable of forming a protective film, the exothermic reaction phases (start, progression and end) are used to achieve the formation of the homogeneous mass.

The bases used in the reaction are preferably selected from oxides, hydroxides, carbonates and / or bicarbonates preferably from those that include an alkali metal or alkaline earth metal, such as, for example, calcium, sodium or potassium

In a preferred embodiment of the process, in the reaction, the acid or base is added once the remaining ingredients have been mixed. In a further embodiment, in the reaction, the acid and the base are added simultaneously once the remaining ingredients have been mixed. In another embodiment of the invention, water is added once the remaining ingredients have been mixed.

By means of the techniques of the present invention, it is possible to coat the acid salt formed, but as also mentioned, it allows to protect additional substances, such as for example pharmacological active principles, oxides, hydroxides, sulfates, carbonates, metal bicarbonates such as for example Copper, zinc, manganese, magnesium, selenium, cobalt, iodine, substances of nutritional interest, etc.

A further advantage of the invention is that apart from the enteric protection achieved, substances can be protected to avoid unwanted reactions with other substances present in food, especially when the coated substance is mixed with food intended for animal consumption. Also the coating obtained is partial or total. BRIEF DESCRIPTION OF THE FIGURES

To complement the description that is being made and in order to help a better understanding of the characteristics of the invention, in accordance with certain preferred examples of practical realization thereof, a set of drawings is attached as an integral part of this description. where for illustrative and non-limiting purposes, the following has been represented:

Figure 1 is a photograph of electron microscopy where zinc oxide particles coated by hydrogenated fat are observed, said particles being obtained by the process of the present invention.

Figure 2 is an electron microscopy image of zinc oxide without having been coated by the process of the present invention.

Figure 3 shows a sodium map made with the ESEM technique for 45% coated sodium butyrate by the process of the present invention.

Figure 4 is an electron microscopy photograph showing particles of sodium butyrate coated with hydrogenated fat, said particles being obtained by the process of the present invention.

Figure 5 is a microscopy image of sodium butyrate without being coated by the process of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION As stated in the present invention, the objective is to protect either: i) an acid salt, or, ii) an acid salt bound to one or more additional substances to be protected, by an exothermic reaction between at least one acid and at least one base, in the presence of at least one protective substance, said protective substance is a hydrogenated fat, a cellulose derivative, a polysaccharide, an acrylate derivative and / or in general substances capable of forming a protective film, which changes state at a certain pH, with suitable solvents, and / or temperature to be homogenized in the product and meets the ability to be protective.

Particularly, cellulose derivatives, polysaccharides and / or acrylate derivatives can be used instead of hydrogenated fat on an acid salt alone or in combination with an additional substance.

To form the enteric coating, in the present invention, an exothermic reaction is carried out between at least one acid, either organic or inorganic, and at least one base, in the presence of at least one protective substance.

For example, in case of using a hydrogenated fat as a protective substance, the heat given off in the exothermic reaction melts the fat and a homogeneous mass formed by the fat and the acid salt is formed and eventually with the additional substance to be protected in case of Let it be added. When the temperature drops and the fat solidifies while the acid salt does, said mass disintegrates and becomes a fine powder with a conglomerate structure of fat coating the acid salt of interest.

It can be seen that, in this embodiment, the protective agent has thermosensitive properties and the thermal effect of the exothermic reaction takes advantage of its properties and allows the high temperature to melt the fat and spread homogeneously throughout the mixture.

On the other hand, in an embodiment of the invention, when the protective agent does not have heat-sensitive properties, it is incorporated before or during the exothermic reaction, allowing to impregnate the entire mixture present and take advantage of morphological changes to create the product of interest in the form of conglomerate.

The process of the present invention begins with the pre-weighing of the raw materials involved in it, in one embodiment, the acid (s) is incorporated and the reaction is started to form the salt (s). of acid (s). More particularly, it can be mentioned that the reaction of the process of the present invention is composed of three distinct phases:

START PHASE.- Where the physical contact of the acid and the base is carried out producing the exothermic chemical reaction.

More particularly, when all the ingredients involved in the reaction have been weighed, and before mixing the acid with the base, in case of using the hydrogenated fat it is preferred to mix it with the rest of the ingredients or with the base, so that in At the time of the reaction, the fat is perfectly distributed. In this phase and until the acid is mixed with the base the product has a solid powder appearance.

PROGRESSION PHASE.- The exothermic chemical reaction starts from the physical mixture of the acid and the base. It is in this phase, where the high temperatures cause the melting of the hydrogenated fat and the mixing effect ensures that all the ingredients are distributed homogeneously, it is also possible to change the morphology of the acid salt and / or of the added active principle. In this morphological change, the size of the particles can fall below 100 nanometers. In this phase, the mixture takes the form of a wet mass, increasing the volume of the initial mixture.

FINAL PHASE When the chemical reaction concludes, the corresponding acid salt is formed. In this phase the wet mass begins to cool and disintegrates into a fine dry powder. In this way, hydrogenated fat happens to occupy a fundamental space in the conglomerate and allows the final product the desired protection.

In this sense, it should be clear that the coating or microencapsulation treatments of the prior art are carried out as the final (finishing) phase of the production, and in the case of the present invention the production and protection are carried out in a single phase of manufacturing.

By way of explanation, it can be mentioned that, in the preferred embodiment of the invention, by incorporating the protector (hydrogenated fat eg) before the chemical reaction starts, the particle of finished product from the particle core is protected out, and in the current processes of coating, coatings or micro-encapsulations the protective layer is an external treatment of the particle to be protected. Hydrogenated fat is any fat that Ambient temperature is solidified due to its hydrogenation treatment, thus raising its melting point.

In another order of ideas, with respect to the components involved in the reaction it can be mentioned that the acid can be organic or inorganic. As organic acids, formic acid, acetic acid, propionic acid, lactic acid, malic acid, fumaric acid, citric acid, capric acid, caproic acid, caprylic acid, butyric acid, isobutyric acid, palmitic acid, stearic acid, oleic acid can be used. , folic acid, pantothenic acid, nicotinic acid or ascorbic acid, among others.

When inorganic acids are used, phosphoric, hydrochloric, sulfuric or nitric acid can be used.

The bases used in the reaction are mineral bases in the form of oxides, hydroxides, carbonates and bicarbonates of elements such as calcium, sodium, potassium, zinc, magnesium, manganese, iron, iodine, cobalt, copper, molybdenum, selenium, or base can be ammonia.

As mentioned, in one embodiment of the invention, an additional substance to be protected may also be present in the reaction which binds to the acid salt formed by the reaction and which is also coated.

As additional substances to be protected, trace elements in general can be used in the form of oxides, sulfates, carbonates and bicarbonates of metals such as zinc, iron, magnesium, manganese, selenium, cobalt, iodine or any other active ingredient with nutritional interest and / or pharmacological and be susceptible to being protected.

The process temperature is at the beginning the ambient temperature and in the end it can reach around 120 ⁵ C due to the exothermic reaction between the acid and the base.

The pressure conditions in the process are varied since optionally vacuum or overpressure can be applied depending on the final product, the thermal effect desired in the procedure, or the machinery that is available.

By means of the techniques of the present invention, it is possible to manufacture acid salts of active ingredients with enteric protection, as long as the active ingredient does not deteriorate at the reaction temperature (eg certain vitamins), but also allows incorporating other substances such as shaped minerals oxides, hydroxides, sulfates and carbonates of some metal such as copper, zinc, manganese, magnesium, selenium, etc.

Once the reaction is carried out, the final product is composed of acid salts either alone or in combination with said at least additional substance, in addition to the protective agent such as hydrogenated fat. In the reaction, the percentage of hydrogenated fat as the initial / final product can range between 10 and 90%, while the minerals are usually in the range of 0 to 70%, and the acid salts, between 10 and 80%.

In one embodiment of the invention, the hydrogenated fat is previously melted in a previous step.

Through the process of the present invention, the following advantages are achieved with respect to traditional techniques, the fusion and dispersion of hydrogenated fat is achieved at the temperature reached by the exothermic reaction and does not require additional sources of heat as in the prior art. .

The procedure can be performed with conventional machinery without using or acquiring specific machinery for microencapsulation or coating.

The procedure allows to have a conglomerate structure, where the final product better supports the manufacturing and milling processes than the classic coated products, which are formed by a core (active principle) and a coating (eg hydrogenated fat). In this regard, it should be noted that the process of the present invention allows obtaining nanoparticles (less than 100 nanometers) of the acid salt and the additional substances.

The protection thus achieved is more flexible than that of other methods described above since traditional methods need a minimum particle size to achieve effective protection. The method of the present invention does not require this point since this characteristic of the product to be protected is not necessary.

The process of the present invention will be more clearly understood with the aid of the following examples that are presented only for illustrative purposes but not limited to the invention.

EXAMPLES:

Example 1. Zinc oxide particles were coated by the process of the present invention, using the following compounds and initial percentages for the reaction:

Zinc Oxide 50.00%

Hydrogenated fat 35.00%

7.60% calcium hydroxide

Formic acid 85% 7.40%

The acid was incorporated when the rest of the ingredients had already been included in the mixer and it was in operation.

After the reaction a fine powder was obtained which was subjected to analysis by microscopy. In Figure 1, the manner in which the contour of the zinc particles is coated with grease is illustrated. The photograph shows the particle size, clearly less than 100 nanometers and the outline of the particle coated with hydrogenated fat.

By way of comparison in Figure 2, a photograph showing zinc oxide in its original state is shown, without having been coated by the process of the present invention, in particular the size of its particles greater than 100 nanometers can be appreciated so It cannot be considered a nanoparticle.

The technology used for microscopy was TEM (Electron Microscopy Transmission), they were observed at 100kV with a Jeol 101 1 (magnification x400k).

Example 2

Sodium Butyrate particles were coated by the process of the present invention, mixing the following components to form the sodium butyrate salt

Table 1.

Butyric acid 140.93

Sodium Carbonate 127.19

Sodium Hydroxide 7.27

Hydrogenated fat 200.00

Silicon dioxide (silica) 36.50

Total: 51 1, 88 Again, the acid was incorporated when the rest of the ingredients had already been included in the mixer and it was in operation.

After finishing the reaction, a sodium map was made using the ESEM technique (environmental scanning electron microscopy) where it was observed, with a FEI Quanta 600 equipment, points that reflect where the sodium is distributed in the photographed particle of Figure 3 ( 45% coated sodium butyrate), which demonstrates the homogeneity of the product.

Figure 4 shows a photograph obtained by microscopy of sodium butyrate where the way in which the contour of the particles is coated can be seen. The photograph shows the particle size clearly below 100 nanometers and the outline of the particle coated with hydrogenated fat.

By way of comparison, a photograph showing the sodium butyrate in its original state is shown in Figure 5, that is, without having been coated by the process of the present invention, in particular the size of its particles greater than 100 nanometers can be appreciated Therefore, it cannot be considered a nanoparticle.

In view of this description and set of figures, the person skilled in the art will be able to understand that the embodiments of the invention that have been described can be combined in multiple ways within the scope of the invention.

Claims

one . Process for obtaining coated acid salts, characterized in that it comprises the steps of: a) performing an exothermic reaction between at least one acid and at least one base to form an acid salt, in the presence of at least one protective substance where in the reaction a homogeneous mass is formed; and, b) let the homogeneous mass that is transformed into a powder where the acid salt is coated by the protective substance cool.

2. A process for obtaining coated acid salts according to claim 1, characterized in that an additional product to be protected is optionally included in the reaction which is bound to the acid salt and which is also covered by the protective substance.

3. Method for obtaining coated acid salts according to claim 2, characterized in that the additional substance to be protected is selected from the group comprising trace elements, pharmacological products, or products of nutritional interest.

4. Method for obtaining coated acid salts according to claim 3, characterized in that the trace element is selected from the group comprising oxides, hydroxides, sulfates, carbonates, bicarbonates of metals such as for example copper, zinc, manganese, magnesium, selenium, cobalt iodine

5. Method for obtaining coated acid salts according to any one of claims 1 to 4, characterized in that the protective substance is selected from the group comprising hydrogenated fats, cellulose derivatives, polysaccharides, acrylate derivatives and substances capable of forming protective films.

Method for obtaining coated acid salts, according to any one of claims 1 to 5, characterized in that the protective substance is fat which, prior to the reaction, is melted or dissolved.

Method for obtaining coated acid salts, according to any one of claims 1 to 5, characterized in that the protective substance is an agent derived from cellulose, polysaccharide, derived from acrylate and / or substances capable of forming protective films which, prior to The reaction dissolves.

Method for obtaining coated acid salts, according to any one of claims 1 to 7, characterized in that, in the reaction, the acid or base is added once the remaining ingredients have been mixed.

9. Method for obtaining coated acid salts according to any one of claims 1 to 8, characterized in that, in the reaction, the acid and the base are added simultaneously once the remaining ingredients have been mixed.

10. Process for obtaining coated acid salts according to any one of claims 1 to 9, characterized in that water is added to the reaction.

eleven . Process for obtaining coated acid salts according to any one of claims 1 to 10, characterized in that the acid, water and base are added simultaneously once the remaining ingredients have been mixed.

12. Process for obtaining coated acid salts according to any one of claims 1 to 1, characterized in that the acid is organic or inorganic.

13. Method for obtaining coated acid salts according to claim 12, characterized in that the acid is an organic acid.

14. A process for obtaining coated acid salts according to any one of claims 1 to 13, characterized in that the base used in the reaction is selected from the group comprising oxides, hydroxides, carbonates or bicarbonates.

15. Process for obtaining coated acid salts according to any one of claims 1 to 14, characterized in that the coating is partial or total enteric.

16. A coated acid salt characterized in that it is obtained by the process according to any of claims 1 to 15.

17. A coated acid salt according to claim 16, characterized in that the coated acid salt has a particle size of less than 100 nanometers.

18. A coated acid salt according to claim 17, characterized in that the coated acid salt and the additional substance have a particle size of less than 100 nanometers.

19. A coated acid salt according to any of claims 16 to 18, characterized in that the protective substance is a hydrogenated fat.