A method for preparing a cysteamine hydrochloride formulation

Abstract

The application discloses a preparation method of cysteamine hydrochloride preparation, and aims at solving the problem that uneven dispersion of solid powder form of an acidic stabilizer and silicon dioxide in mechanical mixing leads to easy oxidation of a product in the prior art.The method comprises the following steps: firstly, adding the acidic stabilizer into liquid cysteamine hydrochloride and stirring until the acidic stabilizer is completely dissolved to obtain a liquid premix; and secondly, mixing, adsorbing and dispersing the liquid premix and a silicon dioxide carrier, and drying to obtain the cysteamine hydrochloride solid preparation.The scheme realizes molecular-level uniform premixing of the acidic stabilizer, avoids oxidation discoloration, reduces the amount of the acidic stabilizer, and makes the product convenient for direct addition by breeders and good in stability.

Description

Technical Field

[0001] This invention relates to the field of animal feed additive processing technology, specifically a method for preparing a cysteine ​​hydrochloride preparation. Background Technology

[0002] Cysteine ​​hydrochloride, as an important feed additive, has significant effects on promoting animal growth and improving meat quality. However, cysteine ​​hydrochloride is originally in liquid form, which presents problems such as inconvenience in addition and high transportation costs when sold directly to farmers. Therefore, existing technologies typically use silica as a carrier to adsorb liquid cysteine ​​hydrochloride onto silica, which is then dried and solidified into a solid powder that is easy for users to mix directly into feed.

[0003] During the solidification process and subsequent storage of cysteamine hydrochloride, it is highly susceptible to oxidation, leading to a greenish tinge in the product appearance, degradation of the active ingredient, and decreased efficacy. To address this issue, current technologies typically employ a solid-solid mixing method, where citric acid, in solid powder form, is mechanically mixed with the silica mixture after adsorbing cysteamine hydrochloride. This utilizes the acidic environment of citric acid to inhibit oxidation, and the addition ratio must be maintained between 1% and 5%.

[0004] However, this existing solid-solid mechanical mixing method has insurmountable drawbacks: when solid powdered citric acid is mechanically mixed with a silica carrier, it can only form a macroscopic distribution at the physical level, making it difficult to achieve uniform dispersion at the molecular level. This results in insufficient citric acid concentration in some areas, where cysteine ​​hydrochloride will still oxidize and turn green. This uneven mixing problem directly leads to poor quality consistency between product batches, and the high amount of citric acid added also increases the raw material cost of feed additives, hindering their large-scale promotion and application. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide a method for preparing cysteine ​​hydrochloride preparations to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, a specific embodiment of the present invention provides a method for preparing a cysteine ​​hydrochloride preparation, comprising the following steps: S1: Add the acidic stabilizer to the container containing liquid cysteine ​​hydrochloride, and stir until the acidic stabilizer is completely dissolved in the liquid cysteine ​​hydrochloride to obtain a liquid premix; In step S1 above, the acidic stabilizer (preferably an organic carboxylic acid) dissolves in liquid cysteine ​​hydrochloride, and then releases hydrogen ions (H+) through ionization. +This process lowers the pH of the system, placing cysteine ​​hydrochloride in an acidic environment. Under acidic conditions, the protonation degree of the thiol group (-SH) in the cysteine ​​hydrochloride molecule increases, significantly reducing its reactivity for oxidation by oxygen. Simultaneously, the acidic environment can complex or passivate any trace metal ions (such as Fe) that may be present in the system. 3+ Cu 2+ (etc.), reducing the catalytic effect of metal ions on the oxidation reaction. Through the above dual mechanism, the acidic stabilizer effectively inhibits the oxidative discoloration of cysteine ​​hydrochloride during preparation and storage, ensuring product stability.

[0007] S2: The liquid premix obtained in step S1 is mixed with a silica carrier, so that the liquid premix is ​​adsorbed and dispersed on the silica carrier. After drying, cysteamine hydrochloride solid formulation is obtained.

[0008] In addition, the method for preparing a cysteamine hydrochloride formulation according to the above-mentioned application may also have the following additional technical features: In one embodiment of this application, the acidic stabilizer is an organic carboxylic acid.

[0009] In one embodiment of this application, the organic carboxylic acid is selected from at least one of citric acid, malic acid, tartaric acid, and fumaric acid.

[0010] In one embodiment of this application, in step S1, the amount of acidic stabilizer added accounts for 0.5% to 2% of the total mass of the liquid cysteine ​​hydrochloride.

[0011] In one embodiment of this application, in step S2, the mass ratio of the liquid premix to the silica carrier is 1:(0.5~3).

[0012] In one embodiment of this application, in step S2, the liquid premix is ​​uniformly applied to the silica carrier by spraying or stirring.

[0013] In one embodiment of this application, the drying is performed using vacuum drying or heating drying.

[0014] In one embodiment of this application, a pulverization step is further included after step S2 to pulverize the dried cysteine ​​hydrochloride solid formulation.

[0015] In one embodiment of this application, the pulverized material is sieved to obtain a finished product that meets the particle size requirements of feed additives.

[0016] The advantages of this invention compared to existing technologies are: (1) This invention completely changes the addition process of acidic stabilizers (such as citric acid) in the traditional preparation process, changing it from "solid-solid mechanical mixing" to "liquid-phase dissolution premixing". Through step S1, the acidic stabilizer achieves uniform dispersion at the molecular level with cysteine ​​hydrochloride in the liquid phase, and then is adsorbed and solidified with silica, which fundamentally solves the problem of product oxidation and greening caused by uneven local mixing, and significantly improves the stability of the product and the consistency of batches.

[0017] (2) Thanks to the premixing uniformity at the liquid phase molecular level, the amount of acidic stabilizer (such as citric acid) added in this invention is significantly reduced from 1%~5% in the prior art to 0.5%~2%. Under the premise of achieving the same or even better antioxidant effect, the amount of raw materials used is greatly reduced, saving the preparation cost of feed additives.

[0018] (3) The acidic stabilizer of the present invention is not limited to citric acid, but can also be a variety of organic carboxylic acids such as malic acid, tartaric acid, and fumaric acid, which broadens the range of raw material selection and has broad industrial application prospects.

[0019] Additional aspects and advantages of this application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of this application. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a flowchart illustrating the preparation method of a cysteine ​​hydrochloride formulation according to an embodiment of the present invention. Figure 2 This is a flowchart illustrating the material flow and process connection of a method for preparing a cysteine ​​hydrochloride preparation according to an embodiment of the present invention.

[0022] Explanation of reference numerals in the attached figures: 1. Liquid cysteamine hydrochloride; 2. Acid stabilizer; 3. Silica carrier. Detailed Implementation

[0023] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] Example 1 like Figures 1 to 2 As shown, an embodiment of the present invention provides a method for preparing a cysteine ​​hydrochloride formulation: A mixing container equipped with a stirring device is prepared beforehand to hold liquid cysteamine hydrochloride 1. During preparation, acidic stabilizer 2 is first added to the container holding the liquid cysteamine hydrochloride 1. After the acidic stabilizer 2 is added, the stirring device on the mixing container is activated to continuously stir the material inside. During stirring, the acidic stabilizer 2 and liquid cysteamine hydrochloride 1 come into full contact and diffuse into each other in the liquid medium until no solid particles remain in the container, indicating that the acidic stabilizer 2 is completely dissolved in the liquid cysteamine hydrochloride 1, thus obtaining a clear and transparent liquid premix. This step achieves uniform molecular-level dispersion of the acidic stabilizer 2 in the liquid cysteamine hydrochloride 1.

[0025] As a preferred embodiment, the stirring speed is 50–300 rpm, the stirring temperature is 20°C–50°C, and the stirring time is 5–30 minutes. During stirring, appropriate heating can be applied to accelerate the dissolution of the acid stabilizer, but the heating temperature should not exceed 50°C to avoid accelerated oxidation or degradation of cysteine ​​hydrochloride due to excessive temperature. The acid stabilizer is considered to have completely dissolved when the liquid in the container is clear and transparent, and no solid particles are visually observed to remain.

[0026] The adsorption and solidification stage then begins. After the liquid premix obtained in step S1 is prepared, it is mixed with the pre-loaded silica support 3. Due to the abundant microporous structure and large specific surface area of ​​the silica support 3, during the mixing process, the liquid phase component of the liquid premix gradually penetrates and disperses on the surface and within the pores of the silica support 3, and is adsorbed and solidified. During this mixing and adsorption process, it is necessary to ensure that the liquid premix is ​​uniformly loaded onto the silica support 3 to avoid excessive local accumulation of liquid phase or uneven wetting of the support.

[0027] After the above adsorption and mixing are completed, the silica carrier 3 with the adsorbed liquid premix is ​​dried to remove excess water or solvent, so that the material is transformed from a wet state into a loose powdery solid, and finally cysteamine hydrochloride solid preparation is obtained.

[0028] Example 2 The preparation process and working principle of this embodiment are basically the same as those of Example 1, except that the raw material selection for acid stabilizer 2 is different.

[0029] In this embodiment, the acidic stabilizer 2 used is an organic carboxylic acid. Specifically, the organic carboxylic acid can be selected from any one or more combinations of citric acid, malic acid, tartaric acid, and fumaric acid. Preferably, in this embodiment, citric acid is selected as the acidic stabilizer 2. Citric acid has excellent solubility in liquid cysteine ​​hydrochloride 1 and can be quickly and completely dissolved through the liquid-phase stirring premixing step of Example 1. While reducing the pH value of the system and inhibiting the oxidation and greening of cysteine ​​hydrochloride, it does not introduce harmful impurities that negatively affect the safety of animal feed.

[0030] As another feasible embodiment of the present invention, the above-mentioned acidic stabilizer can also be malic acid, tartaric acid, or fumaric acid instead of citric acid. Taking malic acid as an example, 1% of the total mass of liquid cysteine ​​hydrochloride is added to liquid cysteine ​​hydrochloride according to the same steps as in Example 1 and stirred until completely dissolved, then mixed with a silica carrier for adsorption. The solid preparation obtained after drying under the same conditions has an antioxidant effect comparable to that when citric acid is used, and the product appearance remains white to off-white without oxidative greening. Therefore, any acidic stabilizer belonging to the organic carboxylic acid class can be used in the preparation method of the present invention, and the present invention is not limited to citric acid alone.

[0031] Example 3 The preparation process and working principle of this embodiment are basically the same as those of Embodiment 1. The difference lies in the precise addition ratio of acidic stabilizer 2 and the control of the mixing ratio of liquid premix and silica carrier 3.

[0032] In this embodiment, during liquid-phase premixing in step S1, the amount of acidic stabilizer 2 added is strictly controlled within a predetermined range of 0.5% to 2% of the total mass of liquid cysteine ​​hydrochloride 1. Compared to the prior art which requires the addition of 1% to 5% solid powder for mixing, this embodiment significantly reduces the amount of acidic stabilizer 2 used, effectively saving production costs.

[0033] The addition amount of acidic stabilizer is controlled at 0.5% to 2% of the total mass of liquid cysteamine hydrochloride, based on the following considerations: when the addition amount is below 0.5%, the pH value of the system does not decrease sufficiently, making it difficult to effectively inhibit the oxidation reaction of cysteamine hydrochloride; when the addition amount is above 2%, although there is limited room for further improvement in the antioxidant effect, excessive acidic stabilizer will increase raw material costs and may adversely affect the palatability of feed. Within the above preferred range, the acidic stabilizer can fully exert its antioxidant stabilizing effect without causing unnecessary cost increases or affecting product quality. It should be noted that, because the present invention uses a liquid-phase premixing process to achieve uniform molecular-level dispersion of the acidic stabilizer, the antioxidant effect can be achieved or even better than that of the 1% to 5% addition amount in the prior art at a relatively low addition amount of 0.5% to 2%.

[0034] Meanwhile, during the adsorption mixing in step S2, the mass ratio of the liquid premix obtained in step S1 to the silica carrier 3 is controlled within the range of 1:(0.5~3). At this ratio, the silica carrier 3 can provide sufficient specific surface area and porosity to completely adsorb the corresponding weight of liquid premix. This ensures that the mixed material will not become an overly wet slurry due to excessive liquid, nor will it result in an excessively low content of active ingredients per unit mass of product due to excessive carrier. This guarantees the smooth progress of the subsequent drying process and the achievement of the product's effective ingredient standards.

[0035] Example 4 The preparation process and working principle of this embodiment are basically the same as those of Embodiment 1. The difference lies in the dispersion method of the liquid premix applied to the silica carrier 3 and the specific means used for drying.

[0036] During the mixing process in step S2, the liquid premix is ​​uniformly applied to the silica carrier 3 by spraying or stirring. Specifically, an atomizing nozzle can be used to uniformly spray the liquid premix as tiny droplets onto the surface of the tumbling silica carrier 3. The droplets are quickly absorbed by the pores after colliding with the carrier surface. Alternatively, the liquid premix can be directly added to a high-speed mixer containing the silica carrier 3. The strong shearing and tumbling action of the stirring blades causes the liquid premix to be rapidly broken up and uniformly dispersed into the silica carrier 3.

[0037] After the mixed adsorption is completed, the obtained material is dried. Drying can be carried out by vacuum drying or heating drying. Vacuum drying can accelerate the evaporation rate of moisture at a lower temperature, avoiding the adverse effects of high temperature on the activity of cysteine ​​hydrochloride. If heating drying is used, the material is baked by hot air circulation or heating jacket to effectively remove moisture until the material can be squeezed into a ball but crumbles easily when released, meeting the drying standard.

[0038] As a preferred embodiment, vacuum drying is performed with a vacuum level controlled between -0.06 MPa and -0.09 MPa, a drying temperature between 40°C and 60°C, and a drying time between 2 and 6 hours, until the material moisture content drops below 5%. Heating drying utilizes a hot air circulating drying chamber with a drying temperature between 50°C and 80°C and a drying time between 3 and 8 hours. During the drying process, excessively high temperatures (above 90°C) or excessively long drying times should be avoided to prevent thermal degradation or accelerated oxidation of cysteine ​​hydrochloride due to high temperatures. The drying endpoint can be determined by periodically sampling and testing the material moisture content; drying can be stopped when the material moisture content is below 5%. The dried material is in a loose powder or granular form, facilitating subsequent crushing and sieving.

[0039] Example 5 The preparation process and working principle of this embodiment are basically the same as those of Example 1. The difference is that a post-processing step is added after the drying process to further improve the physical properties of the finished product.

[0040] After drying and obtaining cysteamine hydrochloride solid dosage form in step S2, the preparation method further includes a pulverization step, in which the dried cysteamine hydrochloride solid dosage form is pulverized. Specifically, the dried lumps or large agglomerates can be fed into a pulverizer, where the large particles are pulverized into fine powder by the shearing and impact action of the blades or hammers inside the pulverizer.

[0041] After grinding, the ground material is sieved through a sieve with a predetermined mesh size to obtain a finished product that meets the particle size requirements for feed additives. The sieving process effectively removes coarse particles or foreign matter that are not completely ground, ensuring that the final product of cysteine ​​hydrochloride solid formulation has uniform particle size, good flowability and dispersibility, making it easy for farmers to mix directly into feed.

[0042] The technical solution described in the above embodiments of this application achieves molecular-level uniform dispersion of the acidic stabilizer 2 in the liquid phase by pre-dissolving the acidic stabilizer 2 in liquid cysteine ​​hydrochloride 1 to form a liquid-phase premix, which is then adsorbed onto the silica carrier 3. Compared to the solid-solid mechanical mixing method of the prior art, this solution effectively avoids the oxidation and greening problem caused by uneven local mixing, and improves the consistency and storage stability of the finished product batches. At the same time, this method controls the amount of acidic stabilizer 2 added to a low range, reducing the cost of raw materials, and the finished product after sieving has good flowability, making it convenient for farmers to add and use directly.

[0043] Obviously, the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention also intends to include these modifications and variations.

Claims

1. A method for preparing a cysteamine hydrochloride formulation, characterized in that, Includes the following steps: S1: Add the acidic stabilizer (2) to the container containing liquid cysteine ​​hydrochloride (1) and stir until the acidic stabilizer (2) is completely dissolved in the liquid cysteine ​​hydrochloride (1) to obtain a liquid premix; S2: The liquid premix obtained in step S1 is mixed with the silica carrier (3) so that the liquid premix is ​​adsorbed and dispersed on the silica carrier (3). After drying, cysteine ​​hydrochloride solid preparation is obtained.

2. The method for preparing a cysteamine hydrochloride formulation according to claim 1, characterized in that, The acidic stabilizer (2) is an organic carboxylic acid.

3. The method for preparing a cysteine ​​hydrochloride formulation according to claim 2, characterized in that, The organic carboxylic acid is selected from at least one of citric acid, malic acid, tartaric acid, and fumaric acid.

4. The method for preparing a cysteine ​​hydrochloride formulation according to claim 1, characterized in that, In step S1, the amount of acidic stabilizer (2) added is 0.5% to 2% of the total mass of liquid cysteine ​​hydrochloride (1).

5. The method for preparing a cysteine ​​hydrochloride formulation according to claim 1, characterized in that, In step S2, the mass ratio of the liquid premix to the silica carrier (3) is 1:(0.5~3).

6. The method for preparing a cysteine ​​hydrochloride formulation according to claim 1, characterized in that, In step S2, the liquid premix is ​​uniformly applied to the silica carrier (3) by spraying or stirring.

7. The method for preparing a cysteine ​​hydrochloride formulation according to claim 1, characterized in that, The drying process employs either vacuum drying or heat drying.

8. The method for preparing a cysteine ​​hydrochloride formulation according to claim 1, characterized in that, The process following step S2 includes a pulverization step, in which the dried cysteine ​​hydrochloride solid formulation is pulverized.

9. The method for preparing a cysteine ​​hydrochloride formulation according to claim 8, characterized in that, The crushed material is sieved to obtain a finished product that meets the particle size requirements for feed additives.

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