A crystal of guanidino acetic acid, its preparation method and application

Abstract

The application provides a guanidoacetic acid crystal and a preparation method and application thereof, and the preparation method of the guanidoacetic acid crystal comprises the following steps: (1) mixing guanidoacetic acid crude product with water, adding an emulsifier and an acid until the guanidoacetic acid crude product is completely dissolved, then adding an alkali into the aqueous solution to react, so as to obtain a reaction solution; (2) performing stage cooling and crystallization on the reaction solution obtained in the step (1), so as to obtain the guanidoacetic acid crystal. Compared with the guanidoacetic acid crystal in the prior art, the guanidoacetic acid crystal prepared by the method has the characteristics of high purity, high fluidity and high moisture resistance, and does not need to rely on a binder and a granulation process to form a final product, and can meet the actual production needs of the feed industry.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, specifically to a guanidinoacetic acid crystal, its preparation method, and its applications. Background Technology

[0002] Guanidinoacetic acid (GAA), a derivative of glycine, is a direct precursor of creatine and phosphocreatine in animals and is mainly used as a food or feed additive. Adding guanidinoacetic acid to animal feed can promote the production of large amounts of phosphate transfer substances (phosphocreatine), thereby achieving multiple effects such as promoting animal growth, improving body shape, enhancing stress resistance and antioxidant properties, improving reproductive performance, increasing energy utilization, and improving meat color. Currently, the conventional method for preparing guanidinoacetic acid in the industry involves reacting cyanamide, an alkaline substance, and glycine, followed by cooling, washing, centrifugation, and drying to obtain the finished product.

[0003] In practical applications, guanidinoacetic acid (guanidine acetic acid) used as a feed additive needs to be mixed with other feed ingredients. However, the pure guanidine acetic acid currently available on the market is in powder form, which has poor flowability. Its bulk density is typically between 300-500 kg / m³, and more than 50% of the particle size distribution is <63 μm, containing significant dust particles. This makes guanidine acetic acid prone to generating a large amount of dust during mixing, and the mixing uniformity is poor, directly resulting in poor application effects and failing to meet the requirements of industrial feed preparation. Furthermore, low-purity guanidine acetic acid powder is prone to absorbing moisture and clumping during storage, further affecting subsequent use. Therefore, guanidine acetic acid usually needs to be granulated into particles with uniform particle size and high mechanical strength through a post-processing granulation process to meet the requirements for use as a feed additive.

[0004] The current mainstream method for preparing guanidinoacetic acid (GA) granules involves adding binders such as starch and hydroxypropyl methylcellulose to GA powder and then granulating it using pelleting equipment. However, the introduction of binders inevitably reduces product purity and may cause unpredictable changes in some components of the feed, affecting the efficiency of animal nutrient absorption. Furthermore, binders are prone to uneven mixing during pellet preparation, resulting in differences in density, strength, flowability, and content uniformity between different batches of pellets, adversely affecting the batch stability of downstream feed products.

[0005] To address the above problems, various improvement schemes have emerged in the existing technology, but significant drawbacks still exist:

[0006] (1) Patent CN118993943B proposes to add a binder during the reaction of glycine and cyanamide to achieve one-time preparation of guanidinoacetic acid granules, reducing the subsequent granulation process. However, the product prepared by this method still contains binder, and the purity of guanidinoacetic acid granules can only reach about 90%, which is far lower than the purity of conventional products on the market. Downstream feed companies need to re-optimize the formula when using it. Moreover, the crystallization rate of this method is only 70%, which causes a lot of waste of raw materials and increases production costs.

[0007] (2) Patent CN118751150A discloses a method for preparing guanidinoacetic acid particles by using nanoscale suspension treatment and multilayer coating technology, combined with ultrasonic dispersion, spray drying, wet granulation and fluidized bed coating. Although no additional binder is added, the preparation process is complicated and requires the use of a low-temperature plasma reactor and low-temperature freezing treatment. The treated pellet cores also need to be coated to enhance moisture resistance, oxidation resistance and flowability, which is not suitable for large-scale production. At the same time, the qualified particle products need to be obtained by screening equipment, and it is impossible to obtain qualified products in one go. Moreover, the patent does not disclose the pass rate of one granulation.

[0008] In summary, existing technologies for the preparation and granulation of guanidinoacetic acid still have many shortcomings in terms of product purity, production process complexity, raw material utilization, product performance stability, and industrial adaptability. Therefore, there is an urgent need in this field to develop a method for preparing granular guanidinoacetic acid that does not rely on binders, has a simple process, produces high-purity products, and has excellent performance, in order to meet the actual production needs of the feed industry. Summary of the Invention

[0009] To address the above problems, the purpose of this invention is to provide a high-flowability guanidinoacetic acid crystal, its preparation method, and its applications. The guanidinoacetic acid crystal provided by this invention is granular and does not require binders or granulation processes to form the final product. It features high purity, high flowability, and strong moisture resistance, meeting the actual production needs of the feed industry.

[0010] As used herein, "bulk density" refers to the density of powdered or granular materials when packed in a certain space, reflecting the degree of compactness of the packing within that space. It includes both loose bulk density and compacted bulk density. In this invention, "bulk density" refers to loose density.

[0011] The term "angle of repose" used in this article refers to the angle between the inclined plane of a cone formed by the natural accumulation of powder or granular materials under gravity and the horizontal plane. It is a core indicator for measuring flowability. The smaller the angle, the easier it is for the particles to slide and the better the flowability; conversely, the larger the angle, the worse the flowability.

[0012] The above-mentioned objective of the present invention is achieved by providing the following technical solution:

[0013] In a first aspect, the present invention provides a method for preparing guanidinoacetic acid crystals, comprising:

[0014] (1) After mixing crude guanidinoacetic acid with water, add emulsifier and acid until the crude guanidinoacetic acid is completely dissolved. Then add alkali to the aqueous solution to react and obtain the reaction solution.

[0015] (2) The reaction solution obtained in step (1) is subjected to staged cooling to crystallize and obtain guanidinoacetic acid crystals.

[0016] According to some embodiments of the present invention, in step (1), crude guanidinoacetic acid is mixed with water, an emulsifier and an acid are added, and the temperature is raised until the crude guanidinoacetic acid is completely dissolved, preferably to 65-75°C, more preferably to 70°C.

[0017] According to some embodiments of the present invention, the method for preparing crude guanidinoacetic acid in step (1) includes the following steps:

[0018] (1-1) Dissolve glycine in water and adjust the pH of the aqueous solution to 6.5-7.0;

[0019] (1-2) Add cyanamide and alkali to the aqueous solution obtained in step (1-1), maintain the pH of the aqueous solution at 8.5-9.0 for reaction, and separate crude guanidinoacetic acid after the reaction is complete.

[0020] The study of this invention shows that adjusting the pH of the aqueous solution in step (1-1) to 6.5-7.0 and maintaining the pH at 8.5-9.0 during the reaction in step (1-2) is more conducive to the formation of guanidinoacetic acid from cyanamide and reduces the content of dicyandiamide.

[0021] According to some embodiments of the present invention, the molar ratio of glycine to cyanamide is 1:1.

[0022] According to some embodiments of the present invention, in step (1-1), glycine is dissolved in water and then heated, preferably to 85-95°C, more preferably to 90°C, and alkali is added to adjust the pH of the aqueous solution to 6.5-7.0.

[0023] According to some embodiments of the present invention, in steps (1-2), the reaction is carried out at 85-95°C, preferably 90°C, for 1-3 hours.

[0024] According to some embodiments of the present invention, in step (1-2), cyanamide and alkali are simultaneously and slowly added to the aqueous solution obtained in step (1-1).

[0025] According to some embodiments of the present invention, the alkali in steps (1), (1-1), and (1-2) is selected from one or more of ammonia, sodium hydroxide, sodium carbonate, and sodium bicarbonate. Preferably, the alkali is added in the form of an aqueous solution of alkali with a mass fraction of 20-40%; more preferably, the alkali is added in the form of an aqueous solution of alkali with a mass fraction of 30%.

[0026] According to some embodiments of the present invention, the emulsifier in step (1) is selected from one or more of sodium fatty acid, potassium fatty acid, Tween 80, and Span. The emulsifier may be C10-C20 sodium fatty acid and / or C10-C20 potassium fatty acid, such as sodium palmitate and / or sodium stearate.

[0027] According to some embodiments of the present invention, the concentration of the emulsifier in the aqueous solution in step (1) is 1–3 g / mL.

[0028] This invention reveals that a specific emulsifier can reduce the interfacial tension between guanidinoacetic acid molecules and water molecules, breaking the agglomeration of guanidinoacetic acid particles in the crude product. This promotes the uniform dispersion of trace hydrophobic impurities to avoid the formation of insoluble microparticles, thus aiding in the dissolution and dispersion of the crude guanidinoacetic acid. It also allows residual soluble impurities such as glycine and cyanamide to fully dissolve. These impurities are removed by centrifugation during subsequent cooling and crystallization because they cannot be embedded in the crystal structure. Simultaneously, the emulsifier can reduce crystal defects caused by localized impurity aggregation, further reducing the content of impurities such as glycine and cyanamide, ultimately ensuring a product purity of ≥98%.

[0029] According to some embodiments of the present invention, in step (1), the ratio of water to crude guanidinoacetic acid is 500 mL-600 mL:100 g, preferably 550 mL:100 g.

[0030] According to some embodiments of the present invention, the acid in step (1) is hydrochloric acid or sulfuric acid. Preferably, the acid is added in the form of an aqueous solution of acid with a mass fraction of 20-40%, more preferably, the acid is added in the form of an aqueous solution of acid with a mass fraction of 30%.

[0031] According to some embodiments of the present invention, the mass ratio of acid to crude guanidinoacetic acid in step (1) is 0.1-0.5. The present invention has found that adding acid in step (1) to adjust the pH of the system to acidic conditions significantly enhances the water solubility of guanidinoacetic acid (containing both acidic carboxyl and basic guanidino groups) under acidic conditions, allowing it to dissolve completely in water. Simultaneously, the acidic environment can convert poorly soluble byproducts into soluble forms.

[0032] According to some embodiments of the present invention, the mass ratio of alkali to crude guanidinoacetic acid in step (1) is 0.09-0.5, preferably 0.1-0.3.

[0033] According to some embodiments of the present invention, the reaction temperature in step (1) is 60-80°C.

[0034] According to some embodiments of the present invention, the reaction time in step (1) is 1-2 hours.

[0035] According to some embodiments of the present invention, the reaction is carried out by stirring while the alkali is slowly added in step (1). Preferably, the stirring speed is 150-300 rpm. This stirring speed ensures uniform mixing of the alkali solution and the system, while avoiding local over-alkaliness or destruction of the crystal nucleus precursor due to excessively fast stirring.

[0036] According to some embodiments of the present invention, the staged cooling crystallization in step (2) includes cooling to 45-55°C and holding for 0.5-2 hours, then cooling to 20-30°C and holding for 0.5-2 hours, and cooling to 0-5°C until the crystals are completely precipitated.

[0037] According to some embodiments of the present invention, the cooling rate in step (2) is 10°C / hour to 20°C / hour, preferably 10-15°C / hour.

[0038] According to some embodiments of the present invention, in step (2), guanidinoacetic acid crystals are separated by centrifugation and dried.

[0039] This invention utilizes the principle of crystallization kinetics to control the crystal nucleus formation rate and crystal growth direction through staged cooling, avoiding problems such as excessive crystal nuclei and uneven crystal size caused by rapid cooling, and finally obtaining granular guanidinoacetic acid crystals with uniform particle size and regular crystal shape.

[0040] In a second aspect, the present invention provides guanidinoacetic acid crystals prepared by the method for preparing guanidinoacetic acid crystals according to the first aspect of the present invention.

[0041] Thirdly, the present invention provides a food or feed additive comprising guanidinoacetic acid crystals prepared by the method for preparing guanidinoacetic acid according to the first aspect of the present invention or guanidinoacetic acid crystals according to the second aspect of the present invention, wherein the food or feed additive is free of binders.

[0042] Compared with the prior art, the present invention has at least the following beneficial effects:

[0043] (1) No need to add traditional binders such as starch and hydroxypropyl methylcellulose, which fundamentally avoids the problem of reduced product purity caused by binders. The final product has high purity, with glycine impurity content ≤0.05%. At the same time, it eliminates batch differences caused by uneven mixing of binders, significantly improves the stability between product batches, and does not require downstream feed companies to re-optimize the formula. It has stronger adaptability and the product is not easy to absorb moisture and clump, further ensuring ease of use.

[0044] (2) The product is granular, free of dust, with a bulk density >600 kg / m³, an angle of repose <30°, and good flowability, making it suitable for industrial preparation of feed;

[0045] (3) The product has excellent storage performance, strong moisture resistance, and is not prone to clumping when stored for a long time;

[0046] (4) The guanidinoacetic acid product produced by this invention has uniform particle size, with more than 80% of the particles having a particle size distribution between 40 mesh and 80 mesh, which can meet the needs of industrial production;

[0047] (5) No complex granulation process and equipment are required, the yield is higher, the production cost is lower, and it is suitable for industrial production. Detailed Implementation

[0048] The present invention will be further described in detail below with reference to specific embodiments. The embodiments given are only for illustrating the present invention and are not intended to limit the scope of the present invention.

[0049] Unless otherwise specified, the experimental methods used in the following examples and comparative examples are conventional methods. Unless otherwise specified, the reagents used in the following examples and comparative examples are commercially available products.

[0050] The yield is calculated as follows: Yield = (actual mass of guanidinoacetic acid after final drying / mass of glycine participating in the reaction) × 100%.

[0051] Example 1: Preparation of particulate guanidinoacetic acid

[0052] (1) Add 117.64g glycine and 258.82g water to the reaction vessel and heat to 75-80℃ to dissolve. After dissolving, heat to 90℃ and add 30% sodium hydroxide aqueous solution to adjust the pH to 6.5-7.0. Simultaneously and slowly add cyanamide in an equimolar amount with glycine and 30% sodium hydroxide aqueous solution to the reaction system, maintaining the pH of the reaction system at 8.5-9.0. After the addition is complete, keep the temperature at 90℃ for 2 hours to complete the reaction. Centrifuge to obtain crude guanidinoacetic acid.

[0053] (2) Mix 100 g of crude guanidinoacetic acid with 550 mL of water, then add 85 mL of 30% hydrochloric acid aqueous solution and sodium fatty acid (Aladdin, catalog number S664774), wherein the concentration of sodium fatty acid in the final aqueous solution is 1 g / mL. Heat to 70℃ to dissolve, control the stirring rate at 200 r / min, and slowly add 33 mL of 30% sodium hydroxide aqueous solution (10 g of sodium hydroxide is added for every 100 g of crude guanidinoacetic acid) dropwise over 1 h. After the reaction is completed, the reaction solution is subjected to staged cooling treatment. In the first stage, the temperature is lowered to 50℃ and kept at 1 h. In the second stage, the temperature is lowered to 25℃ and kept at 1 h. Finally, the temperature is directly lowered to 0℃. The cooling rate in the first and second stages is 15℃ / h. After centrifugation and drying, granular guanidinoacetic acid crystals are obtained.

[0054] Examples 2-7

[0055] Based on Example 1, Examples 2-7 set different reaction conditions in step (2) to prepare granular guanidinoacetic acid crystals. The specific reaction conditions of each example are shown in Table 1. The yield, content, particle size distribution and impurity content of cyanamide, dicyandiamide and glycine of the granular guanidinoacetic acid crystals obtained in each example are shown in Table 2.

[0056] Comparative Example 1: No emulsifier added

[0057] (1) Add 117.64g glycine and 258.82g water to the reaction vessel and heat to 75-80℃ to dissolve. After dissolving, heat to 90℃ and add 30% sodium hydroxide aqueous solution to adjust the pH to 6.5-7.0. Simultaneously and slowly add cyanamide in an equimolar amount with glycine and 30% sodium hydroxide aqueous solution to the reaction system, maintaining the pH of the reaction system at 8.5-9.0. After the addition is complete, keep the temperature at 90℃ for 2 hours to complete the reaction. Centrifuge to obtain crude guanidinoacetic acid.

[0058] (2) Mix 100 g of crude guanidinoacetic acid with 550 mL of water, add 85 mL of 30% hydrochloric acid aqueous solution, heat to 90 °C to dissolve, control the stirring rate at 200 r / min, and slowly add 33 mL of 30% sodium hydroxide aqueous solution (10 g of sodium hydroxide per 100 g of crude guanidinoacetic acid) dropwise over 1 h. After the reaction is completed, the reaction solution is subjected to staged cooling treatment. In the first stage, the temperature is lowered to 50 °C and kept at 1 h. In the second stage, the temperature is lowered to 25 °C and kept at 1 h. Finally, the temperature is directly lowered to 0 °C. The cooling rate in the first and second stages is 15 °C / h. After centrifugation and drying, granular guanidinoacetic acid crystals are obtained.

[0059] The yield, content, particle size distribution, and contents of impurities cyanamide, dicyandiamide, and glycine of the granular guanidinoacetic acid crystals obtained in Comparative Example 1 are shown in Table 2.

[0060] Comparative Example 2: Preparation of powdered guanidinoacetic acid

[0061] 117.64 g g of glycine and 258.82 g of water were added to a reaction vessel and heated to 75-80 °C to dissolve them. After dissolution, the temperature was raised to 90 °C, and a 30% sodium hydroxide aqueous solution was added to adjust the pH to 6.5-7.0. An equimolar amount of cyanamide and a 30% sodium hydroxide aqueous solution were simultaneously and slowly added dropwise to the reaction system, maintaining the pH at 8.5-9.0. After the addition was complete, the reaction was maintained at 90 °C for 2 hours until completion. The mixture was then cooled to room temperature, and the pH was adjusted to 7.8 with acid. After centrifugation and drying, powdered guanidinoacetic acid was obtained. The content, particle size distribution, and contents of impurities cyanamide, dicyandiamide, and glycine are shown in Table 2.

[0062]

[0063]

[0064] As can be seen from the tests in Table 2:

[0065] The powdered guanidinoacetic acid obtained in Comparative Example 2 not only had a low guanidinoacetic acid content, but also a significantly high proportion of impurities, failing to meet the standards for high-quality feed additives.

[0066] The granular guanidinoacetic acid crystals obtained in Comparative Example 1, which did not use emulsifiers, showed significant improvement in purity and impurity content compared to Comparative Example 2. However, the glycine content was still 0.32% (glycine is a key factor that causes the product to easily clump), posing a significant risk of clumping and failing to meet the quality requirements for industrial production.

[0067] The granular guanidinoacetic acid crystals prepared using hydrophilic emulsifiers in Examples 1, 2 and 4-7 exhibited excellent core performance indicators: guanidinoacetic acid content was ≥98%, cyanamide ≤0.01%, dicyandiamide ≤0.05%, and glycine ≤0.05%, while the crystallization particle size distribution was uniform, and all parameters met industrial standards.

[0068] The granular guanidinoacetic acid crystals prepared in Example 3 using a lipophilic emulsifier were slightly inferior to those in Examples 1, 2, and 4-7 in terms of glycine content and uniformity of crystal size, but still met the quality requirements for industrial production.

[0069] The above results fully demonstrate that using emulsifiers, and more preferably emulsifiers containing strong hydrophilic groups, can achieve multiple key effects simultaneously—reducing the risk of product clumping by lowering glycine content, ensuring the uniformity of initial crystallization, improving the solubility of guanidinoacetic acid in water, preventing rapid precipitation of materials during cooling, and ultimately promoting the growth of large, uniform crystals, allowing the product's various indicators to meet industrial standards.

[0070] Performance tests: The performance parameters of the granular guanidinoacetic acid crystals prepared in Example 4, the powdered guanidinoacetic acid crystals prepared in Comparative Example 2, and the commercially available guanidinoacetic acid granular product (Evonik, product number 240917HG51) were tested respectively. The comparison results of data such as particle size distribution, stability, hygroscopicity, flowability, and bulk density are shown in Table 3.

[0071]

[0072] As can be seen from Table 3, the granular guanidinoacetic acid crystals prepared in Example 4 of the present invention exhibit better performance than the powdered product of Comparative Example 2: (1) the proportion of fine powder is very small and the particle size distribution is more reasonable, indicating that its dust risk is low; (2) it does not clump during storage and has lower hygroscopicity, indicating that its stability is stronger; (3) the angle of repose is smaller and the bulk density is higher, indicating that its flowability and packaging and transportation economy are better.

[0073] Furthermore, compared with commercially available guanidinoacetic acid granules, the granular guanidinoacetic acid crystals prepared in Example 4 of this invention can achieve the same technical effects as commercially available guanidinoacetic acid granules without adding binders and with a simplified preparation process.

Claims

1. A method for preparing guanidinoacetic acid crystals, comprising: (1) After mixing crude guanidinoacetic acid with water, add emulsifier and acid until the crude guanidinoacetic acid is completely dissolved. Then add alkali to the aqueous solution to react and obtain the reaction solution. (2) The reaction solution obtained in step (1) is subjected to staged cooling to crystallize and obtain guanidinoacetic acid crystals.

2. The method for preparing guanidinoacetic acid crystals according to claim 1, in step (1), crude guanidinoacetic acid is mixed with water, then an emulsifier and acid are added and the temperature is raised to the point where the crude guanidinoacetic acid is completely dissolved, preferably to 65-75°C, more preferably to 70°C.

3. The method for preparing guanidinoacetic acid crystals according to claim 1 or 2, wherein the method for preparing crude guanidinoacetic acid in step (1) includes the following steps: (1-1) Dissolve glycine in water and adjust the pH of the aqueous solution to 6.5-7.0; (1-2) Add cyanamide and alkali to the aqueous solution obtained in step (1-1), maintain the pH of the aqueous solution at 8.5-9.0 for reaction, and separate the crude guanidinoacetic acid after the reaction is complete; Preferably, in step (1-1), glycine is dissolved in water and then heated, preferably to 85-95°C, more preferably to 90°C, and alkali is added to adjust the pH of the aqueous solution to 6.5-7.0; Preferably, in step (1-2), cyanamide and alkali are added simultaneously and slowly to the aqueous solution obtained in step (1-1); Preferably, in step (1-2), the reaction is carried out at 85-95°C, more preferably 90°C, for 1-3 hours; Preferably, the molar ratio of glycine to cyanamide is 1:

1.

4. The method for preparing guanidinoacetic acid crystals according to any one of claims 1-3, wherein the alkali in steps (1), (1-1), and (1-2) is selected from one or more of ammonia, sodium hydroxide, sodium carbonate, and sodium bicarbonate; preferably, the alkali is added in the form of an aqueous solution of alkali with a mass fraction of 20-40%; more preferably, the alkali is added in the form of an aqueous solution of alkali with a mass fraction of 30%. Preferably, the acid in step (1) is hydrochloric acid or sulfuric acid; preferably, the acid is added in the form of an aqueous solution of acid with a mass fraction of 20-40%, more preferably, the acid is added in an aqueous solution of acid with a mass fraction of 30%.

5. The method for preparing guanidinoacetic acid crystals according to any one of claims 1-4, wherein the emulsifier in step (1) is selected from one or more of sodium fatty acid, potassium fatty acid, Tween 80 and Span; preferably, the concentration of the emulsifier in the aqueous solution in step (1) is 1–3 g / mL.

6. The method for preparing guanidinoacetic acid crystals according to any one of claims 1-5, wherein in step (1), the ratio of water to crude guanidinoacetic acid is 500 mL-600 mL:100 g, preferably 550 mL:100 g; Preferably, in step (1), the mass ratio of acid to crude guanidinoacetic acid is 0.1-0.5; Preferably, in step (1), the mass ratio of alkali to crude guanidinoacetic acid is 0.09-0.5, more preferably 0.1-0.

3.

7. The method for preparing guanidinoacetic acid crystals according to any one of claims 1-6, wherein the reaction temperature in step (1) is 60-80℃; Preferably, the reaction time in step (1) is 1-2 hours; Preferably, in step (1), the alkali is added slowly while stirring to carry out the reaction. More preferably, the stirring speed is 150-300 rpm.

8. The method for preparing guanidinoacetic acid crystals according to any one of claims 1-7, wherein the staged cooling crystallization in step (2) includes cooling to 45-55°C and holding for 0.5-2 hours, then cooling to 20-30°C and holding for 0.5-2 hours, and cooling to 0-5°C until the crystals are completely precipitated; Preferably, the cooling rate in step (2) is 10℃ / hour to 20℃ / hour, more preferably 10℃ to 15℃ / hour. Preferably, in step (2), guanidinoacetic acid crystals are separated by centrifugation and dried.

9. Guanidoacetic acid crystals prepared by the method according to any one of claims 1-8.

10. A food or feed additive comprising guanidinoacetic acid crystals prepared by the method according to any one of claims 1-8 or guanidinoacetic acid crystals according to claim 9, wherein, The food or feed additives do not contain binders.

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