Purification method for reducing aluminum ion residues in leucine

Abstract

The invention discloses a purification method for reducing aluminum ion residues in leucine, which comprises the following steps: 1, dissolving a leucine sample in deionized water until the concentration is 10.0-22.0 g / L, adding hydrochloric acid to adjust the pH value, heating to 75-85 DEG C for dissolving, slowly stirring, and cooling to room temperature; 2, enabling the aqueous solution to pass through amino phosphonic acid chelate resin at a flow rate of 5.0-10.0 BV, and collecting effluent; and step 3, adding activated carbon into the effluent for decoloration for 40 minutes, and carrying out refined filtration and decarburization to obtain a decolorized solution. The invention relates to the technical field of amino acid purification, and according to the purification method, macroporous structure chelating resin with a weakly acidic active group (aminophosphonic acid) is adopted to selectively adsorb aluminum ions, and an acid-soluble water-washing process is adopted, so that trace aluminum ion residues in leucine are effectively reduced. The method is low in equipment requirement and simple to operate, the content of aluminum ions can be reduced to 0.2 ppm or below, the leucine loss is extremely low, the repeated utilization rate of the resin is high, and the production cost is greatly reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of amino acid purification, and specifically to a purification method for reducing the residual aluminum ions in leucine. Background Art

[0002] Leucine, with the chemical name of 2-amino-4-methylpentanoic acid, is one of the essential amino acids in the human body and has been widely used in fields such as food, health products, and medicine. Leucine is used in food fields such as nutritional supplements and flavor enhancers, and also in pharmaceutical fields such as amino acid infusions, comprehensive amino acid preparations, and hypoglycemic agents. There are many quality standard control items for leucine raw materials, but the content detection item of aluminum element is often ignored by manufacturers. It is reported that the large accumulation of aluminum element in the human body will pose a serious threat to people's physical health. For example, it will damage the central nervous system of the human body and affect the digestive system of the human body, resulting in various chronic diseases. As a raw material drug, the residual aluminum element in leucine directly affects the quality control of amino acid preparations and indirectly affects the medication safety of patients.

[0003] Currently, the commonly used methods for reducing aluminum content include chemical precipitation, membrane filtration, ion exchange, and adsorption. The precipitation method is to add different precipitants to form insoluble precipitates with aluminum ions, thereby reducing the aluminum ion content. For example, in the patent CN102965506B, Ge Xinfang et al. used benzoate as a precipitant to remove aluminum from rare earth liquor. However, the aluminum content in the leucine solution is extremely low, making it difficult to form precipitates, and the precipitant is very likely to introduce other impurities, affecting the quality of leucine. Therefore, this method is not suitable for removing aluminum from leucine. The membrane filtration method mainly relies on the selective permeability of the membrane to separate the components in the liquid. For example, in the patent CN107761101A, Chen Yun et al. used an NF membrane separation system to separate chemical polishing waste liquid, obtaining high-concentration aluminum waste liquid and purified solution. However, this method has a complex device, high membrane cost, and difficult equipment maintenance. The adsorption method is to use a porous solid adsorbent to adsorb one or several components in the water sample on its surface. For example, in the patent CN09182791B, Li Jinhui et al. used the method of organic acid complexation - porous polyvinylbenzene resin and activated carbon adsorption to achieve the purpose of aluminum removal. However, the removal effect on aluminum ions with a content lower than 10 ppm is not significant, and the chelating agent has poor selectivity. The ion exchange method is to exchange the ions in the solution with the ions on the ion exchanger to remove certain ions in the solution. This method has good selectivity, high efficiency, simple operation, and low cost. As long as a suitable stationary phase is selected, specific impurities can be selectively removed without affecting other substances. For example, in CN111921565A, Zhao Liwei et al. invented a method for reducing the aluminum content in amino acid injection, using a strong acid cation resin and / or a metal adsorbent (high-purity mercapto-modified silica gel) to carry out an adsorption reaction on aluminum ions under stirring conditions to achieve the purpose of aluminum removal. However, when the resin and the metal adsorbent are used in combination, the subsequent recovery and treatment are troublesome, the reuse rate is low, and the silica gel is easily inhaled, which may cause harm to the human body.

[0004] According to literature retrieval, the existing aluminum removal technologies are mainly applied to solutions with relatively high aluminum content such as high-concentration industrial wastewater and rare earth liquor, and there are few purification processes used to reduce the residual trace aluminum ions in leucine. Therefore, aiming at the defects existing in the existing technology, providing a purification method for reducing trace aluminum ions in leucine is an urgent problem to be solved by those skilled in the art. Summary of the Invention

[0005] (I) Technical Problem to be Solved

[0006] In view of the deficiencies of the existing technology, the present invention provides a purification method for reducing the residual aluminum ions in leucine, solving the problems of poor removal effect and high cost of aluminum ion impurities in leucine in the existing technology.

[0007] (II) Technical Solution

[0008] To achieve the above object, the present invention provides the following technical solutions: A purification method for reducing the residual aluminum ions in leucine, comprising the following steps:

[0009] Step 1: Dissolve the leucine sample in deionized water to a concentration of 10.0 - 22.0 g / L, adjust the pH with hydrochloric acid, heat to 75 - 85 °C for dissolution, stir slowly and cool to room temperature;

[0010] Step 2: Pass the aqueous solution through an amino phosphonic acid chelating resin at a flow rate of 5.0 - 10.0 BV, and collect the effluent;

[0011] Step 3: Add activated carbon to the effluent for decolorization for 40 min, and obtain a decolorized solution after fine filtration and carbon removal;

[0012] Step 4: The decolorized solution enters a concentration evaporator for concentration, and the concentrated feed liquid is concentrated to a solid - liquid content of 3.5 - 4.5%;

[0013] Step 5: Cool and crystallize the above - mentioned concentrated solution, control the temperature at 15 °C - 20 °C, centrifuge the crystallization solution, then wash it with deionized water, and then centrifuge again to obtain a wet product, and obtain a purified leucine product after drying.

[0014] As a further preference, in the above - mentioned Step 1, the pH of the leucine solution is adjusted to 2.0 - 5.0 with 1M hydrochloric acid.

[0015] As a further preference, in the above - mentioned Step 2, the washing flow rate of the amino phosphonic acid chelating resin is 6.0 BV - 8.0 BV.

[0016] As a further preference, in the above - mentioned Step 2, the dosage of the amino phosphonic acid chelating resin is 8 - 20 times the mass of leucine.

[0017] As a further preference, in the above - mentioned Step 3, the dosage of activated carbon is 0.8 - 1.5%, and the decolorization temperature is 60 - 80 °C.

[0018] As a further preference, in the above - mentioned Step 4, the concentration conditions in the concentration evaporator are: control the temperature at 70 - 80 °C, the vacuum degree at - 0.07 - - 0.1 Mpa, and concentrate to a solid - liquid content of 3.8 - 4.5%.

[0019] As a further preference, in the above - mentioned Step 5, the amount of deionized water used for washing is 1.0 - 2.0 times the mass of wet leucine.

[0020] As a further preference, the reduced aluminum ion content in the leucine is within 0.2 ppm.

[0021] (III) Beneficial effects

[0022] The present invention provides a purification method for reducing the residual aluminum ions in leucine, which has the following beneficial effects:

[0023] 1. The purification method for reducing the residual aluminum ions in leucine selectively adsorbs aluminum ions by using a macroporous chelating resin with a weakly acidic active group (aminophosphonic acid), and adopts an acid dissolution and water washing process, effectively reducing the residual trace aluminum ions in leucine. This method has low equipment requirements and simple operation, can reduce the aluminum ion content to below 0.2 ppm, with extremely low loss of leucine, high resin reuse rate, and greatly reduces the production cost.

[0024] 2. The present invention does not add chemical reagents with complex components such as precipitants, nor uses osmotic membranes with low service life and high cost; the method of using aminophosphonic acid chelating resin to reduce aluminum ions avoids introducing other chemical impurities into leucine, effectively ensures the purity and product quality of leucine, and at the same time, the repeated use of the resin greatly reduces the raw material cost.

[0025] 3. The present invention simply and efficiently reduces the aluminum ion concentration in leucine, and the leucine with the reduced aluminum ion concentration can be used for the preparation of injection preparations, ensuring the quality control of amino acid preparations and ensuring the safety of clinical medication. Description of the Drawings

[0026] Figure 1 It is the test report of the aluminum ion content in leucine of Examples 1 - 3 and Comparative Example 1 of the present invention;

[0027] Figure 2 It is the test report of the aluminum ion content in the leucine raw material used in the present invention. Detailed Embodiments

[0028] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0029] Example 1

[0030] The present invention provides a purification method for reducing the residual aluminum ions in leucine, including the following steps:

[0031] Add 80.0 g of raw material leucine to 4.0 L of deionized water. After stirring evenly, slowly add 1 M hydrochloric acid to adjust the pH to 3.0. Heat to 80 °C until dissolved and clarified, then stir slowly and cool to room temperature to obtain an aqueous leucine solution. Subsequently, adsorb it at a flow rate of 6 BV through 800.0 g of amino phosphonic acid chelating resin to obtain an eluate; add 0.8 g of medicinal activated carbon to the eluate, control the temperature at 65 °C, stir for decolorization for 40 min, and then filter through a 0.22 μm fine filter to remove carbon to obtain a decolorized solution; put the decolorized solution into a concentration evaporator for concentration, control the temperature at 75 °C, vacuum -0.095 Mpa, concentrate the feed liquid to a solid content of 4.0%, stop concentration and transfer it to a cooling crystallization tank, slowly cool it to 15 °C at a rate of 20 °C / h, keep the feed liquid stirred for 30 min and then filter, then wash it with 1.5 times deionized water, filter until no liquid drips, and then put it into a vacuum drying oven and dry at 60 °C for 4 hours to obtain a leucine product with low aluminum ion residue.

[0032] The content of aluminum ions in the leucine obtained in this example was detected to be 0.1171 ppm.

[0033] Example 2

[0034] The present invention provides a purification method for reducing the aluminum ion residue in leucine, which includes the following steps:

[0035] Add 110.0 g of raw material leucine to 5.0 L of deionized water. After stirring evenly, slowly add 1 M hydrochloric acid to adjust the pH to 3.2. Heat to 80 °C until dissolved and clarified, then stir slowly and cool to room temperature to obtain an aqueous leucine solution. Subsequently, adsorb it at a flow rate of 7 BV through 1210.0 g of amino phosphonic acid chelating resin to obtain an eluate; add 1.1 g of medicinal activated carbon to the eluate, control the temperature at 65 °C, stir for decolorization for 40 min, and then filter through a 0.22 μm fine filter to remove carbon to obtain a decolorized solution; put the decolorized solution into a concentration evaporator for concentration, control the temperature at 80 °C, vacuum -0.095 Mpa, concentrate the feed liquid to a solid content of 4.2%, stop concentration and transfer it to a cooling crystallization tank, slowly cool it to 20 °C at a rate of 20 °C / h, keep the feed liquid stirred for 30 min and then filter, then wash it with 1.0 times deionized water, filter until no liquid drips, and then put it into a vacuum drying oven and dry at 60 °C for 4 hours to obtain a leucine product with low aluminum ion residue.

[0036] The content of aluminum ions in the leucine obtained by the present invention was detected to be 0.1751 ppm.

[0037] Example 3

[0038] The present invention provides a purification method for reducing the aluminum ion residue in leucine, which includes the following steps:

[0039] Add 210.0 g of raw material leucine to 10.0 L of deionized water. After stirring evenly, slowly add 1 M hydrochloric acid to adjust the pH to 2.9. Heat to 80 °C until dissolved and clarified, then stir slowly and cool to room temperature to obtain an aqueous leucine solution. Subsequently, adsorb it at a flow rate of 6 BV through 2100.0 g of amino phosphonic acid chelating resin to obtain an eluate; add 1.9 g of medicinal activated carbon to the eluate, control the temperature at 65 °C, stir for decolorization for 40 min, and then filter through a 0.22 μm fine filter to remove carbon to obtain a decolorized solution; put the decolorized solution into a concentration evaporator for concentration, control the temperature at 75 °C, vacuum -0.095 Mpa, concentrate the feed liquid to a solid content of 4.1%, stop concentration and transfer it to a cooling crystallization tank, slowly cool it to 15 °C at a rate of 20 °C / h, keep the feed liquid stirring for 30 min and then filter, then wash it with 1.2 times deionized water, filter until no liquid drips, and put it into a vacuum drying oven, dry it at 60 °C for 4 hours to obtain a leucine product with low aluminum ion residue.

[0040] The content of aluminum ions in the leucine obtained in the present invention is detected to be 0.1431 ppm.

[0041] Comparative Example 1

[0042] Add 110.0 g of raw material leucine to 5.0 L of deionized water. After stirring evenly, slowly add 1 M hydrochloric acid to adjust the pH to 3.0. Heat to 80 °C until dissolved and clarified, then stir slowly and cool to room temperature to obtain an aqueous leucine solution. Subsequently, adsorb it at a flow rate of 7 BV through 1210.0 g of strong acid cation resin to obtain an eluate; add 1.1 g of medicinal activated carbon to the eluate, control the temperature at 65 °C, stir for decolorization for 40 min, and then filter through a 0.22 μm fine filter to remove carbon to obtain a decolorized solution; put the decolorized solution into a concentration evaporator for concentration, control the temperature at 75 °C, vacuum -0.095 Mpa, concentrate the feed liquid to a solid content of 4.2%, stop concentration and transfer it to a cooling crystallization tank, slowly cool it to 15 °C at a rate of 20 °C / h, keep the feed liquid stirring for 30 min and then filter, then wash it with 1.0 times deionized water, filter until no liquid drips, and put it into a vacuum drying oven, dry it at 60 °C for 4 hours to obtain a leucine product with low aluminum ion residue.

[0043] Comparing Examples 1 - 3, the content of aluminum ions in the leucine obtained in Comparative Example 1 after replacing the amino phosphonic acid chelating resin with a strong acid cation resin is detected to be 0.5938 ppm. The content of aluminum ions does not reach below 0.2 ppm. Therefore, Comparative Example 1 can illustrate a problem, that is, when the amino phosphonic acid chelating resin is replaced with other types of resins, the content of aluminum ions in the finally measured leucine significantly does not meet the requirements (the content does not reach below 0.2 ppm). Therefore, Comparative Example 1 also verifies the reliability of adsorbing aluminum ions through the amino phosphonic acid chelating resin as expected.

[0044] In addition, the attached instruction Figure 2The data shown is the content of aluminum ions in the leucine raw material, and its specific value is basically around 10 ppm (9.6314 ppm, 9.6083 ppm). That is to say, the content of aluminum ions in the raw material before being treated by the method adopted in the present invention is significantly on the high side. After the above-mentioned leucine raw material is treated by the three separate experiments adopted in Examples 1-3 of the present invention, the final content value of aluminum ions is generally lower than 0.2 ppm, which also fully proves the success of the method involved in the present invention.

[0045] Finally, it should be specifically noted that our company is willing to bear relevant responsibilities for the authenticity of the above-mentioned values. If necessary, our company is willing to list relevant supporting materials one by one as relevant evidence.

[0046] Meanwhile, the content not described in detail in this specification belongs to the prior art well-known to those skilled in the art.

[0047] It should be noted that the electrical components appearing in this article are all electrically connected to the external main controller and 220V or 380V mains. And the main controller can be a conventional known device such as a computer for control. Its control principle, internal structure, and control switch mode are all conventional means of the prior art and are directly cited here without further elaboration. In this article, relational terms such as first and second are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the term "comprising", "including" or any other variant thereof is intended to cover non-exclusive inclusion, so that a process, method, article or device comprising a series of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article or device.

[0048] Although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principle and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A purification method for reducing residual aluminum ions in leucine, comprising the following steps: Step 1: Dissolve the leucine sample in deionized water to a concentration of 10.0-22.0 g / L, add hydrochloric acid to adjust the pH, heat to 75-85°C to dissolve, stir slowly and cool to room temperature; Step 2: passing the aqueous solution through the aminophosphonic acid chelating resin at a flow rate of 5.0-10.0 BV, and collecting the effluent; Step 3: Add activated carbon to the effluent for decolorization for 40 minutes, and obtain a decolorized liquid after fine filtration and decarbonization; Step 4: The decolorized liquid enters the concentration evaporator for concentration, and the liquid is concentrated to a solid-liquid content of 3.5-4.5%; Step 5: Cool the concentrated solution and crystallize it, control the temperature at 15°C-20°C, centrifuge the crystallized solution, rinse it with deionized water, centrifuge it again to obtain a wet product, and dry it to obtain a purified leucine product.

2. The purification method for reducing residual aluminum ions in leucine according to claim 1, characterized in that: In the step 1, the pH of the leucine solution is adjusted to 2.0-5.0 using 1M hydrochloric acid.

3. The purification method for reducing residual aluminum ions in leucine according to claim 1, characterized in that: In the step 2, the washing flow rate of the aminophosphonic acid chelating resin is 6.0 BV-8.0 BV.

4. The purification method for reducing residual aluminum ions in leucine according to claim 1, characterized in that: In the step 2, the amount of aminophosphonic acid chelating resin used is 8-20 times the mass of leucine.

5. A purification method for reducing residual aluminum ions in leucine according to claim 1, characterized in that: In the step 3, the amount of activated carbon used is 0.8-1.5%, and the decolorization temperature is 60-80°C.

6. The purification method for reducing residual aluminum ions in leucine according to claim 1, characterized in that: In the step 4, the concentration conditions in the concentration evaporator are: controlling the temperature at 70-80°C, the vacuum degree at -0.07--0.1Mpa, and concentrating to a solid-liquid content of 3.8-4.5%.

7. The purification method for reducing residual aluminum ions in leucine according to claim 1, characterized in that: In the step 5, the amount of deionized water used for elution is 1.0-2.0 times that of the wet leucine.

8. The purification method for reducing residual aluminum ions in leucine according to any of claims 1 to 7, characterized in that: The reduced aluminum ion content in the leucine is within 0.2 ppm.

Images