A method for recycling the saline wastewater produced in the production of crude heparin sodium

Abstract

The present invention belongs to the technical field of wastewater treatment, and particularly relates to a method for recycling saline wastewater produced in the production of crude heparin sodium. According to the comprehensive analysis of the source and composition of the crude heparin sodium wastewater, the present invention simplifies the wastewater treatment process, shortens the process time, is conducive to the recovery of heparin sodium, reduces resource waste, recycles sodium chloride, solves the problem of difficult treatment due to the excessive content of sodium chloride in the wastewater, and has low ammonia nitrogen in the effluent and high protein removal rate. The treated wastewater is recycled to the salting-out + enzyme section process for reuse, which has no impact on the extraction of crude heparin sodium. It conforms to the national policies of resource utilization, energy conservation and emission reduction, and environmental protection.

Description

Technical Field

[0001] The present invention relates to the technical field of wastewater, and particularly relates to a method for recycling saline wastewater produced in the production of crude heparin sodium. Background Art

[0002] Heparin sodium is a natural anticoagulant drug with a wide range of biological functions and medicinal values, such as anticoagulation, clarification of blood lipids, reduction of cholesterol, anti-inflammation, anti-allergy, anti-virus, and reduction of blood lipids. Heparin drugs have been the most widely used and effective anticoagulant drugs in the world for more than 70 years of clinical treatment.

[0003] Heparin sodium is first extracted from the small intestinal mucosa of fresh and healthy live pigs and made into crude heparin sodium, which can only be used clinically after being refined. The production process of crude heparin sodium includes processes such as raw material treatment, enzymatic hydrolysis extraction, ion exchange adsorption, elution, resin regeneration, etc. During the production process, a large amount of saline wastewater will be discharged. The components of the wastewater include: crude heparin sodium, water, 3-5% (W / W) sodium chloride, insoluble impurities such as grease, organic substances such as proteins, and part of ammonia nitrogen, etc. This type of wastewater is characterized by a high concentration of organic substances and a high salt content. Direct discharge seriously pollutes the environment and also causes waste of resources. There are some existing treatment methods for the saline wastewater produced in the production of crude heparin sodium. For example, in CN201410522339.8, a method and system for treating high-concentration saline wastewater in heparin sodium production, proteins and sodium chloride are removed by acid precipitation + sodium chloride electrolysis, but the actual effect is far from reaching the standard. Acid precipitation is to change the solution pH or charge status to precipitate and separate proteins from the colloidal solution. This method is not applicable to all proteins, and the removal rate is not high. At the same time, the sodium chloride in the wastewater cannot be completely directly converted into hydrochloric acid and sodium hydroxide solutions. At present, chlor-alkali production enterprises electrolyze a 300g / L sodium chloride solution (about 24% W / W), and generally the sodium chloride solution after electrolysis is about 200g / L (about 16% W / W). However, the Baume degree of sodium chloride in heparin sodium wastewater is only 3-5% (W / W), and there are also interferences from other organic solvents such as proteins. The electrolysis efficiency will be very low. Therefore, this method cannot effectively treat heparin sodium saline wastewater theoretically. CN202011353770.6, a new process for treating heparin sodium wastewater with efficient protein recovery, recovers proteins and separates and recovers proteins by means of resin adsorption, alcohol precipitation, polymerization precipitation, acid precipitation, salting out, etc. However, the sodium chloride in the wastewater is not treated, and aluminum trichloride, ethanol, trichloroacetic acid, a small amount of sodium chloride, etc. are added during the process of recovering proteins, increasing the difficulty of treating saline wastewater and not completely solving the problem of heparin sodium wastewater discharge. In CN201810034367.3, the comprehensive utilization method of casing factory wastewater is for the mixed wastewater of casing wastewater and heparin sodium wastewater, adding a composite emulsifier, ferric chloride, calcium chloride, zinc chloride, and a flocculant to separate proteins in the wastewater. However, relying solely on chemical substances to separate proteins has relatively low efficiency, and chemical substances are added to the wastewater. First, it is difficult to treat, and second, it increases metal ions such as calcium, iron, and zinc. Direct recycling of the saline wastewater will affect both heparin sodium extraction and casing treatment, and actually cannot be directly recycled.CN201711345781.8 A method and device for treating industrial wastewater extracted from animals. This invention uses a combined treatment method of ultrafiltration, nanofiltration, electrodialysis, and biochemical method to treat high-salt industrial wastewater extracted from animals. The main purpose is to recover solid salt and protein. The process steps are cumbersome and the energy consumption is relatively high. Especially in the process of recovering solid salt, since the salt content in industrial wastewater extracted from animals is about 3-5%, compared with the evaporation and concentration process, the salt content is very low. The energy consumption for evaporating to solid salt is relatively high, and the purity of the evaporated solid salt is not high, with a high impurity content and it is difficult to be directly used as a product. In most of the existing methods, attention is mainly paid to separating proteins and sodium chloride in the wastewater to meet the discharge standard, or directly recovering proteins, etc., and there is no method for treating the wastewater to be recyclable.

[0004] Therefore, how to solve the problem of high sodium chloride content in the wastewater and at the same time the treatment problem that the wastewater has no impact on the heparin sodium extraction process after recycling is an urgent problem to be solved for the healthy development of the industry. Summary of the Invention

[0005] In view of the problems in the background technology, the present invention provides a method for recycling saline wastewater in the production of crude heparin sodium, which can effectively remove proteins, organic matter, heavy metals, and ammonia nitrogen in the saline wastewater of crude heparin sodium, hardly add new chemical substances, and at the same time recycle the treated saline wastewater to the crude heparin sodium salt hydrolysis + enzymatic hydrolysis process for reuse, which will not affect the extraction of crude heparin sodium, recycle sodium chloride, solve the problem of difficult treatment of high-salt wastewater, improve resource utilization rate, and reduce the cost of wastewater treatment.

[0006] To achieve the above object, the present invention provides a method for recycling saline wastewater in the production of crude heparin sodium, including the following steps:

[0007] (1) Collect the saline wastewater produced in the production process of crude heparin sodium, and after filtration treatment with an NC membrane, obtain waste liquid I;

[0008] The main components of the collected saline wastewater are: crude heparin sodium, 3-5% (W / W) sodium chloride, 10-20 mg / L of calcium and magnesium ions, 80-100 mg / L of sulfate radicals, 2-3% (W / W) of grease, proteins, some ammonia nitrogen and other organic matters.

[0009] (2) Adjust the pH of waste liquid I to 8-9 with a sodium hydroxide solution with a mass fraction of 5%-8%, adsorb the wastewater with an anion resin for 2 h, control the temperature at 50-60 °C, and perform filtration treatment to obtain waste liquid II;

[0010] (3) Slowly adjust the pH of waste liquid II to 6-7 at a certain stirring rate, add a certain proportion of a composite reagent to waste liquid II, stir for 10-15 min and then perform filtration treatment to obtain waste liquid III;

[0011] (4) Add a certain amount of zeolite to the waste liquid III and stir for 10 min. Control the temperature at 40 - 50 °C, and obtain waste liquid IV after filtration.

[0012] (5) After the waste liquid IV is filtered through a nanofiltration membrane, the permeate can be recycled and reused in the intestinal mucosa salting-out + enzymatic hydrolysis process.

[0013] At this time, the sodium chloride concentration and purity in the nanofiltration membrane permeate can be directly recycled and reused in the crude heparin sodium salting-out + enzymatic hydrolysis process, recycling sodium chloride and solving the problem of difficult treatment due to the high content of sodium chloride in the wastewater.

[0014] In step (1), the pore size of the NC membrane is 0.2 μm or 0.45 μm, and the operating temperature is 20 - 30 °C. In steps (2), (3), and (4), the filtration treatment is carried out using a bag filter with a precision of 0.45 - 1.0 μm.

[0015] After adsorption in step (2), the anion resin is eluted, alcohol-precipitated, and dried to obtain crude heparin sodium.

[0016] In step (5), the molecular weight cut-off of the nanofiltration membrane is 200 Da - 500 Da, and the operating temperature is 20 - 30 °C. Preferably, in step (3), the composite reagent is composed of stearylamine hydrochloride 60% - 70%, sodium lauroyl glutamate 10% - 20%, and L-lysine-L-aspartate 10 - 20% by mass percentage, and the addition ratio is 0.75 - 1% (W / W) of the waste liquid II.

[0017] The added composite reagent is ionic, carrying both positive charges and a small number of negative charges in the solution, and adsorbing and removing proteins through the action of electric charges. At the same time, L-lysine-L-aspartate can couple with some proteins due to having multiple special groups (-COOH) and precipitate together. When the composite reagent is at a certain concentration and exceeds the protein saturation binding site, it will cause protein unfolding, form surface active clusters, and the proteins will interact with each other, promoting protein aggregation and more effectively removing proteins. The composite reagent also contains hydrophobic groups, which will combine with the hydrophobic groups of the organic matter in the solution when facing the solution, and can remove some organic matter in the solution. The precipitated composite substance is removed by filtration, and a small amount of residual composite reagent can be removed in subsequent steps without affecting the overall wastewater.

[0018] Zeolite itself carries negative charges. Since stearylamine hydrochloride in the composite reagent carries positive charges, it is captured by the negatively charged adsorption active sites on the zeolite surface through electrostatic attraction. Sodium lauroyl glutamate and L-lysine-L-aspartate both carry strong polar functional groups such as -COOH and -NH2, and can be adsorbed on the outer surface of the zeolite and removed.

[0019] Preferably, the addition amount of zeolite in step (4) is 50 - 60 g / L. Zeolite has a framework structure with channels and cavities containing exchangeable cations in the framework, and any conventional zeolite for industrial use can be used. After filtration in steps (1), (3), and (4), the solid crude protein is mixed and dried at 30 - 35 °C, and then used as a fertilizer or feed additive after drying.

[0020] The beneficial effects of the present invention are as follows:

[0021] (1) The present invention recovers the remaining heparin sodium in the wastewater, removes impurities (including proteins, organic matters, metal ions, ammonia nitrogen, etc.), and meets the standard for recycling the wastewater to the heparin sodium salt hydrolysis + enzymatic hydrolysis process, containing 3 - 4% (W / W) sodium chloride. The process flow and process conditions play a key role. For example, after adding zeolite, the heating condition can promote the ion exchange between sodium ions in the wastewater and the ions in the zeolite, increase the pore size of the zeolite, improve the efficiency of ammonia nitrogen removal, and at the same time, the exchanged calcium, magnesium, and iron metal ions will also promote the precipitation of a small amount of proteins, reducing the impact on the heparin sodium salt hydrolysis + enzymatic hydrolysis process. At the same time, it can also reduce the sodium chloride concentration in the wastewater to a certain extent, and this concentration is just within the range suitable for the sodium chloride concentration in the heparin sodium extraction salt hydrolysis and enzymatic hydrolysis processes, without negative impacts.

[0022] (2) The composite reagent added in the present invention can adsorb proteins in the wastewater to form surface active clusters, and the proteins will interact with each other to promote protein aggregation, significantly improving the protein removal rate. The composite reagent contains a hydrophobic group and can combine with the hydrophobic groups of some organic matters in the solution, thus removing some organic matters in the solution.

[0023] (3) As a treatment process close to the end, the zeolite in the present invention can not only remove ammonia nitrogen and a small amount of residual proteins, but also adsorb and remove the composite reagent brought in from the previous step, ensuring the availability of the wastewater.

[0024] (4) During the entire wastewater treatment process, the present invention ensures the impurity removal effect without introducing difficult-to-treat organic matters, etc. At the same time, it is directly recycled to the intestinal mucosa salt hydrolysis + enzymatic hydrolysis process, which has no impact on heparin extraction, recycles sodium chloride, solves the problem of difficult treatment due to excessive sodium chloride content in the wastewater, and reduces the treatment cost. Description of the Drawings

[0025] Figure 1 It is a process flow chart of the method for recycling the salt-containing wastewater in the production of crude heparin sodium of the present invention. Detailed Embodiments

[0026] The present invention will be described in detail below with reference to specific embodiments

[0027] Example 1

[0028] (1) Collect the saline wastewater produced in the crude heparin sodium production process, filter it through a 0.45 μm nitrocellulose membrane (NC membrane) at an operating temperature of 25°C to obtain Waste Liquid I;

[0029] (2) Adjust the pH of Waste Liquid I to 8.5, adsorb the wastewater with an anion resin for 2 h at a temperature controlled at 55°C, and obtain Waste Liquid II after filtering through a 0.45 μm cloth bag;

[0030] (3) At a certain stirring rate, slowly adjust the pH of Waste Liquid II to 6.5, add a composite reagent (60% stearylamine hydrochloride, 20% sodium lauroyl glutamate, 20% L-lysine-L-aspartate) with a mass of 0.75% to Waste Liquid II, stir for 10 - 15 min, and then filter through a 0.45 μm cloth bag at an operating temperature of 25°C to obtain Waste Liquid III;

[0031] (4) Add 50 g / L of zeolite (75% clinoptilolite, 25% mordenite) to Waste Liquid III, stir for 10 min at a temperature controlled at 40 - 50°C, and obtain Waste Liquid IV after filtering through a 0.45 μm cloth bag;

[0032] (5) Filter Waste Liquid IV through a nanofiltration membrane with a molecular weight cut-off of 300 Da at an operating temperature of 25°C, and the permeate can be recycled and reused in the heparin sodium salt hydrolysis + enzymatic hydrolysis process.

[0033] Comparative Example 1

[0034] In step (3), the composite reagent was not added, and the other raw materials and steps were the same as in Example 1:

[0035] (1) Collect the saline wastewater produced in the crude heparin sodium production process, filter it through a 0.45 μm NC membrane at an operating temperature of 25°C to obtain Waste Liquid I;

[0036] (2) Adjust the pH of Waste Liquid I to 8.5, adsorb the wastewater with an anion resin for 2 h at a temperature controlled at 55°C, and obtain Waste Liquid II after filtering through a 0.45 μm cloth bag;

[0037] (3) At a certain stirring rate, slowly adjust the pH of Waste Liquid II to 6.5, stir for 10 - 15 min, and then filter through a 0.45 μm cloth bag at an operating temperature of 25°C to obtain Waste Liquid III;

[0038] (4) Add 50 g / L of zeolite to Waste Liquid III, stir for 10 min at a temperature controlled at 40 - 50°C, and obtain Waste Liquid IV after filtering through a 0.45 μm cloth bag;

[0039] (5) The waste liquid Ⅳ is filtered through a nanofiltration membrane with a molecular weight cut-off of 300 Da at an operating temperature of 25°C, and the permeate can be recycled and reused in the heparin sodium salt hydrolysis + enzymatic hydrolysis process.

[0040] Example 2

[0041] (1) The salt-containing wastewater produced in the crude heparin sodium production process is collected and filtered through a 0.2-μm NC membrane at an operating temperature of 25°C to obtain waste liquid Ⅰ;

[0042] (2) The pH of waste liquid Ⅰ is adjusted to 8.6, and the wastewater is adsorbed with an anion resin for 2 h at a temperature controlled at 55°C. After filtration through a 0.45-μm cloth bag, waste liquid Ⅱ is obtained;

[0043] (3) At a certain stirring rate, the pH of waste liquid Ⅱ is slowly adjusted to 6.5, and a composite reagent with a mass of 0.75% (70% stearylamine hydrochloride, 20% sodium lauroyl glutamate, 10% L-lysine-L-aspartate) is added to waste liquid Ⅱ. After stirring for 10 - 15 min, it is filtered through a 0.45-μm cloth bag at an operating temperature of 25°C to obtain waste liquid Ⅲ;

[0044] (4) 55 g / L of zeolite (75% clinoptilolite, 25% mordenite) is added to waste liquid Ⅲ and stirred for 10 min at a temperature controlled at 40 - 50°C. After filtration through a 0.45-μm cloth bag, waste liquid Ⅳ is obtained;

[0045] (5) The waste liquid Ⅳ is filtered through a nanofiltration membrane with a molecular weight cut-off of 300 Da at an operating temperature of 25°C, and the permeate can be recycled and reused in the heparin sodium salt hydrolysis + enzymatic hydrolysis process.

[0046] Comparative Example 2

[0047] Replace the NC membrane in step (1) with an ultrafiltration membrane, and the other raw materials and steps are the same as in Example 2:

[0048] (1) The salt-containing wastewater produced in the crude heparin sodium production process is collected and filtered through a 0.1-μm ultrafiltration membrane at an operating temperature of 25°C to obtain waste liquid Ⅰ;

[0049] (2) The pH of waste liquid Ⅰ is adjusted to 8.5, and the wastewater is adsorbed with an anion resin for 2 h at a temperature controlled at 55°C. After filtration, waste liquid Ⅱ is obtained;

[0050] (3) At a certain stirring rate, the pH of waste liquid Ⅱ is slowly adjusted to 6.5, and a composite reagent with a mass of 0.75% (70% stearylamine hydrochloride, 20% sodium lauroyl glutamate, 10% L-lysine-L-aspartate) is added to waste liquid Ⅱ. After stirring for 10 - 15 min, it is filtered through a 0.45-μm cloth bag at an operating temperature of 25°C to obtain waste liquid Ⅲ;

[0051] (4) Add 55 g / L of zeolite (75% clinoptilolite and 25% mordenite) to the waste liquid III, stir for 10 min, control the temperature at 40 - 50 °C, and obtain waste liquid IV after filtration;

[0052] (5) Filter the waste liquid IV through a nanofiltration membrane with a molecular weight cut-off of 300 Da, at an operating temperature of 25 °C, and the permeate can be recycled and reused in the heparin sodium desalting + enzymatic hydrolysis process.

[0053] Example 3

[0054] (1) Collect the salt-containing wastewater produced in the crude heparin sodium production process, filter it through a 0.2-μm NC membrane at an operating temperature of 25 °C to obtain waste liquid I;

[0055] (2) Adjust the pH of the waste liquid I to 8.6, adsorb the wastewater with an anion resin for 2 h, control the temperature at 55 °C, and obtain waste liquid II after filtration through a 0.45-μm cloth bag;

[0056] (3) Slowly adjust the pH of the waste liquid II to 6.5 at a certain stirring rate, add 1% by mass of a composite reagent (60% stearylamine hydrochloride, 20% sodium lauroyl glutamate, 20% L-lysine-L-aspartate) to the waste liquid II, stir for 10 - 15 min, and then filter through a 0.45-μm cloth bag at an operating temperature of 25 °C to obtain waste liquid III;

[0057] (4) Add 50 g / L of zeolite (75% clinoptilolite and 25% mordenite) to the waste liquid III, stir for 10 min, control the temperature at 40 - 50 °C, and obtain waste liquid IV after filtration through a 0.45-μm cloth bag;

[0058] (5) Filter the waste liquid IV through a nanofiltration membrane with a molecular weight cut-off of 300 Da, at an operating temperature of 25 °C, and the permeate can be recycled and reused in the heparin sodium desalting + enzymatic hydrolysis process.

[0059] Comparative Example 3

[0060] The temperature in step (4) was not controlled and was carried out at room temperature, and the other raw materials and steps were the same as in Example 3:

[0061] (1) Collect the salt-containing wastewater produced in the crude heparin sodium production process, filter it through a 0.1-μm ultrafiltration membrane at an operating temperature of 25 °C to obtain waste liquid I;

[0062] (2) Adjust the pH of the waste liquid I to 8.5, adsorb the wastewater with an anion resin for 2 h, control the temperature at 55 °C, and obtain waste liquid II after filtration through a 0.45-μm cloth bag;

[0063] (3) At a certain stirring rate, slowly adjust the pH of Waste Liquid II to 6.5. Add a composite reagent (60% stearylamine hydrochloride, 20% sodium lauroyl glutamate, 20% L-lysine-L-aspartate) with a mass of 1% to Waste Liquid II. After stirring for 10 - 15 min, filter it through a 0.45-μm cloth bag. The operating temperature is 25°C to obtain Waste Liquid III;

[0064] (4) Add 50 g / L of zeolite to Waste Liquid III and stir for 10 min. After filtering through a 0.45-μm cloth bag, Waste Liquid IV is obtained;

[0065] (5) Waste Liquid IV is filtered through a nanofiltration membrane with a molecular weight cut-off of 300 Da. The operating temperature is 25°C, and the permeate can be recycled and reused in the heparin sodium hydrolysis + enzymatic hydrolysis process.

[0066] After the temperature rises, the ability of ammonia nitrogen to overcome the surface boundary film resistance of zeolite increases, which promotes the migration of ammonia nitrogen adsorbed on the zeolite surface along the micropores of zeolite into the interior of zeolite, and the adsorption capacity of zeolite also increases. The increase in temperature is also beneficial to the cation exchange between sodium ions and the cations in zeolite, making the effective pore size of zeolite larger, the steric hindrance smaller, and the internal diffusion rate faster, and the adsorption capacity also increases. The wastewater treated in the above-mentioned examples was measured, and the specific results are shown in Table 1:

[0067]

[0068]

[0069] It can be clearly seen from the above detection results that: using the methods disclosed in Examples 1, 2, and 3 of the present invention to perform resource treatment on heparin sodium wastewater has obvious effects, and the removal rates of protein and organic matter are over 95%; compared with Comparative Examples 1, 2, and 3, the contents of calcium ions, magnesium ions, sulfate radicals, COD, ammonia nitrogen, etc. in the obtained filtrate are reduced more significantly, the removal rates of protein and organic matter are higher, and the efficiency is more obvious.

[0070] Take 40 g of fresh pig small intestine mucosa, add the wastewater treated in Examples 1, 2, and 3 in proportion, and adjust the pH to about 8.5 - 9. Add alkaline protease, place it in a constant temperature water bath at 55°C and stir for 3 h, then place it at 90°C to inactivate the enzyme, filter, and measure the heparin content by the sheep plasma method.

[0071] Take 40 g of fresh pig small intestine mucosa, add the sodium chloride solution added in proportion, adjust the pH to about 8.5 - 9. Add alkaline protease, place it in a constant temperature water bath at 55°C and stir for 3 h, then place it at 90°C to inactivate the enzyme, filter, and measure the heparin content by the sheep plasma method. The specific results are as

[0072] shown in Table 2:

[0073] Heparin titer / (U / ml) Heparin titer / (U / g) Example 1 13.568 67.84 Example 2 13.827 69.14 Example 3 13.314 66.57 Comparative Example 1 13.915 69.58

[0074] It can be clearly seen from the above test results that after the heparin sodium wastewater is treated resourcefully by the methods disclosed in Embodiments 1, 2, and 3 of the present invention and recycled to the salting-out + enzymatic hydrolysis process, there is almost no impact on heparin extraction.

Claims

1. A method for recycling the saline wastewater produced in the production of crude heparin sodium, characterized in that, It includes the following steps: (1) Collect the saline wastewater produced in the crude heparin sodium production process, and after filtering and treating it with an NC membrane, obtain waste liquid I; the saline wastewater for crude heparin sodium production is the saline wastewater discharged in all production processes of crude heparin sodium, and its main components include: crude heparin sodium, 3-5% (W / W) sodium chloride, 10-20 mg / L of calcium and magnesium ions, 80-100 mg / L of sulfate radicals, 2-3% (W / W) of grease, protein, and partial ammonia nitrogen; (2) Adjust the pH of waste liquid I to 8-9, adsorb the wastewater with an anion resin, control the temperature at 50-60 °C, and perform filtration treatment to obtain waste liquid II; (3) Under stirring conditions, adjust the pH of waste liquid II to 6-7, add a composite reagent to waste liquid II, stir and then perform filtration treatment to obtain waste liquid III; the composition of the composite reagent by mass percentage is: 60%-70% stearylamine hydrochloride, 10%-20% sodium lauroyl glutamate, 10-20% L-lysine-L-aspartate, and the addition ratio is 0.75-1% (W / W) of waste liquid II; (4) Add zeolite to waste liquid III and stir, control the temperature at 40-50 °C, and after filtration treatment, obtain waste liquid IV; the composition of the zeolite by mass percentage is: 75% clinoptilolite, 25% mordenite; the addition amount of the zeolite is 50-60 g / L; (5) After waste liquid IV is filtered through a nanofiltration membrane, the permeate is recovered and reused in the intestinal mucosa salting-out + enzymatic hydrolysis process.

2. The method for recycling the saline wastewater produced in the production of crude heparin sodium according to claim 1, wherein: In step (1), the pore size of the NC membrane is 0.2 μm or 0.45 μm, and the filtration treatment temperature is 20-30 °C.

3. The method for recycling the saline wastewater produced in the production of crude heparin sodium according to claim 1, wherein: In steps (2), (3), and (4), the filtration accuracy of the filtration treatment is 0.45-1.0 μm; in step (5), the molecular weight cut-off of the nanofiltration membrane is 200 Da-500 Da, and the operating temperature is 20-30 °C.

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