A histidine purification system based on membrane separation and continuous ion exchange technology

Abstract

The utility model relates to medical processing equipment technical field, concretely relates to a kind of histidine purification system based on membrane separation and continuous ion exchange technology, it includes primary ceramic membrane filtration unit, secondary nanofiltration membrane decolorization unit, tertiary high-pressure nanofiltration membrane concentration unit and four continuous ion exchange unit by pipeline sequentially connected in series.The histidine purification system based on membrane separation and continuous ion exchange technology is designed, it avoids the use of activated carbon, production efficiency is higher and environmental pollution is smaller, significantly reduce comprehensive energy consumption while further make that final product impurity is less, purity is high, batch stability is significantly superior to traditional process, satisfy pharmaceutical grade histidine standard.

Description

Technical Field

[0001] This utility model relates to the field of pharmaceutical processing equipment technology, and in particular to a histidine purification system based on membrane separation and continuous ion exchange technology. Background Technology

[0002] Histidine is a basic building block of proteins and one of the 21 amino acids that make up human proteins. Its main function is to maintain the healthy development of various tissues in the body, especially the myelin sheath that wraps nerve cells, ensuring the transmission of information from the brain to all parts of the body. It has some effect in treating mental illnesses and certain types of sexual dysfunction. Currently, the industrial production process of histidine mainly involves activated carbon decolorization, fixed-bed purification, and evaporator concentration. This method is mature and stable, but it has high production costs, activated carbon decolorization can easily lead to a dirty and chaotic production environment, and fixed-bed production has low efficiency. Utility Model Content

[0003] To address the aforementioned technical problems, the purpose of this invention is to provide a histidine purification system based on membrane separation and continuous ion exchange technology. This histidine purification system is designed based on membrane separation and continuous ion exchange technology, which avoids the use of activated carbon, resulting in higher production efficiency and less environmental pollution. It significantly reduces overall energy consumption while further improving the final product by reducing impurities, increasing purity, and enhancing batch stability compared to traditional processes, thus meeting pharmaceutical-grade histidine standards.

[0004] To achieve the above-mentioned technical effects, the present invention adopts the following technical solution: In a first aspect, the present invention provides a histidine purification system based on membrane separation and continuous ion exchange technology, comprising the following processing units connected in series via pipelines: A primary ceramic membrane filtration unit is used for solid-liquid separation of histidine fermentation broth, wherein the primary ceramic membrane filtration unit comprises a primary ceramic membrane separation component with a separation pore size of 0.05–0.2 μm; A secondary nanofiltration membrane decolorization unit is used to decolorize the dialysate from a primary ceramic membrane filtration unit. The secondary nanofiltration membrane decolorization unit includes a secondary nanofiltration membrane separation component with a separation pore size of 200–1000 Daltons. A three-stage high-pressure nanofiltration membrane concentration unit is used to concentrate the dialysate from the two-stage nanofiltration membrane decolorization unit. The three-stage high-pressure nanofiltration membrane concentration unit includes a three-stage high-pressure nanofiltration membrane assembly with a separation pore size of less than 100 Daltons and an operating pressure of 45–55 bar. The four-stage continuous ion exchange unit is used to purify the concentrate from the three-stage high-pressure nanofiltration membrane concentration unit through ion exchange.

[0005] Furthermore, the primary ceramic membrane filtration unit includes: Primary raw material tank, used to receive and temporarily store histidine fermentation broth; A primary feed pump, the inlet of which is connected to a primary raw material tank, and the outlet of which is connected to the inlet of the primary ceramic membrane separation module; And a primary dialysis tank, connected to the dialysis fluid outlet of the primary ceramic membrane separation assembly.

[0006] Furthermore, the primary ceramic membrane filtration unit also includes: A primary reflux pipeline connects the concentrate outlet of the primary ceramic membrane separation module to the primary raw material tank.

[0007] Furthermore, the secondary nanofiltration membrane decolorization unit further includes: The secondary feed tank is used to receive and temporarily store the dialysis fluid from the primary ceramic membrane filtration unit; A secondary feed pump, the inlet of which is connected to a secondary feed tank, and the outlet of which is connected to the inlet of the secondary nanofiltration membrane separation module; The secondary dialysis tank is connected to the dialysis fluid outlet of the secondary nanofiltration membrane separation assembly.

[0008] Furthermore, the secondary nanofiltration membrane decolorization unit also includes: A secondary reflux pipeline connects the concentrate outlet of the secondary nanofiltration membrane separation module to the secondary feed tank.

[0009] Furthermore, the three-stage high-pressure nanofiltration membrane concentration unit includes: The three-stage feed tank is used to receive and temporarily store the dialysis solution from the secondary nanofiltration membrane decolorization unit; A three-stage feed pump has its inlet connected to a three-stage feed tank and its outlet connected to the inlet of the three-stage high-pressure nanofiltration membrane module. The three-stage dialysis tank is connected to the dialysis fluid outlet of the three-stage high-pressure nanofiltration membrane module.

[0010] Furthermore, the three-stage high-pressure nanofiltration membrane concentration unit also includes: A three-stage reflux pipeline connects the concentrate outlet of the three-stage high-pressure nanofiltration membrane module to the three-stage feed tank.

[0011] Furthermore, the four-stage continuous ion exchange unit includes an adsorption zone, a water washing and regeneration zone, a regeneration zone, a water top desorption zone, a desorption zone, a product top water zone, and a washing zone arranged sequentially. The adsorption zone is used to receive the concentrate output from the three-stage high-pressure nanofiltration membrane concentration unit; The water washing and regeneration zone is used for the injection of pure water; The regeneration zone is used for regenerant injection; The water-top desorption zone is used for injecting pure water. The desorption zone is used for injecting the desorption fluid; The product top water zone includes a first reverse column, which is located downstream of the desorption zone and is used for reverse injection of the product tail liquid flowing out of the desorption zone. The washing area is used for injecting pure water.

[0012] Preferably, a by-product top water zone is provided between the adsorption zone and the water washing and regeneration zone. The by-product top water zone includes at least one second reverse column, which is used to reverse inject the product tail liquid flowing out of the adsorption zone. The product tail liquid mainly contains by-products other than histidine.

[0013] Preferably, the adsorption zone adopts a multi-level parallel-connected topology, which includes at least 3 sets of parallel adsorption column units connected in series.

[0014] Compared with the prior art, the beneficial effects of this utility model are as follows: This invention provides a histidine purification system based on membrane separation and continuous ion exchange technology. Through its innovative design of coupling continuous ion exchange with membrane separation technology, it overcomes the inherent defects of traditional processes (activated carbon decolorization + fixed-bed purification + evaporation concentration), and has the following significant advantages: First, the histidine purification system provided by this invention completely replaces activated carbon decolorization, achieving clean production by directly decolorizing the ceramic membrane dialysis solution using nanofiltration membranes (200-1000 Da). This avoids the dust pollution, waste carbon disposal problems, and unsanitary production environment associated with activated carbon use, significantly reducing solid waste treatment costs and meeting green manufacturing requirements. Simultaneously, this system employs a three-stage high-pressure nanofiltration membrane module (<100 Da, 45-55 bar) to pre-concentrate the decolorized solution. This step replaces the traditional high-energy-consuming evaporator, significantly reducing overall energy consumption.

[0015] Secondly, the histidine purification system provided by this invention effectively realizes resource recycling. In particular, the continuous ion exchange system achieves efficient recycling of water resources and chemical reagents through zoned operation, and the membrane system has a long lifespan and low maintenance cost.

[0016] In summary, this system forms a precise separation gradient through three-stage membrane filtration and combines it with continuous ion exchange for refined purification. In this continuous ion exchange device, the adsorption, elution, and regeneration processes are operated continuously. This not only solves the problems of equipment idleness and low production efficiency caused by the intermittent operation of traditional fixed beds, but also greatly increases production capacity and makes the product purity more stable. At the same time, the final product has fewer impurities, higher purity, and batch stability that is significantly better than traditional processes, meeting the pharmaceutical-grade histidine standard. Attached Figure Description

[0017] Figure 1A schematic diagram of the overall structure of a histidine purification system based on membrane separation and continuous ion exchange technology is provided for an embodiment of this utility model; The attached diagram is labeled as follows: A11, primary reflux pipeline; A12, primary feed tank; A13, primary feed pump; A14, primary ceramic membrane separation module; A15, primary dialysis tank; A21, secondary reflux pipeline; A22, secondary feed tank; A23, secondary feed pump; A24, secondary nanofiltration membrane separation module; A25, secondary dialysis tank; A31, tertiary reflux pipeline; A32, tertiary feed tank; A33, tertiary feed pump; A34, tertiary high-pressure nanofiltration membrane module; A35, tertiary dialysis tank; 41, adsorption zone; 42, by-product top water zone; 43, water washing and regeneration zone; 431, regeneration zone; 44, water top desorption zone; 441, desorption zone; 45, product top water zone; 46, washing zone; 50, heat exchanger. Detailed Implementation

[0018] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings. These embodiments are merely illustrative of the present invention and should not be construed as limiting the scope of protection of the present invention.

[0019] Unless otherwise specified, in this utility model, terms such as "length," "width," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," "axial," "radial," "circumferential," "x-direction," "y-direction," and "z-direction" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing this utility model and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, the terms used to describe orientation or positional relationships in this utility model are for illustrative purposes only and should not be construed as limiting this patent. For those skilled in the art, the specific meaning of the above terms can be understood in conjunction with the accompanying drawings and according to the specific circumstances.

[0020] Please see Figure 1 This embodiment provides a histidine purification system based on membrane separation and continuous ion exchange technology, comprising a primary ceramic membrane filtration unit, a secondary nanofiltration membrane decolorization unit, a tertiary high-pressure nanofiltration membrane concentration unit, and a quaternary continuous ion exchange unit connected in series via pipelines. The primary ceramic membrane filtration unit includes a primary ceramic membrane separation component A14 with a separation pore size of 0.05–0.2 μm, used for solid-liquid separation of histidine fermentation broth. The secondary nanofiltration membrane decolorization unit includes a secondary nanofiltration membrane separation component A24 with a separation pore size of 200–1000 Daltons, used for decolorizing the dialysate from the primary ceramic membrane filtration unit. The tertiary high-pressure nanofiltration membrane concentration unit includes a tertiary high-pressure nanofiltration membrane component A34 with a separation pore size of less than 100 Daltons and an operating pressure of 45–55 bar, used for concentrating the dialysate from the secondary nanofiltration membrane decolorization unit. The quaternary continuous ion exchange unit is used for ion exchange purification of the concentrate from the tertiary high-pressure nanofiltration membrane concentration unit.

[0021] The above histidine purification system operates as follows: In the first step, the histidine fermentation broth enters the primary ceramic membrane separation module A14 (pore size 0.05-0.2μm) to remove suspended solids from the histidine fermentation broth. The resulting dialysate I (solid content 2%-4%, transmittance ≥10%, conductivity 10000-20000us / cm) is then processed in the next step.

[0022] The second step involves using a secondary nanofiltration membrane separation module A24 (pore size 200-1000 Daltons) to decolorize dialysate I after it has been treated with a ceramic membrane, producing dialysate II (solid content 1%-2%, transmittance ≥50%, conductivity ≤15000us / cm).

[0023] The third step involves using a three-stage high-pressure nanofiltration membrane module A34 (pore size less than 100 Daltons) to concentrate dialysate II, producing concentrate III (solid content ≥12%) and dialysate III (solid content 0, transmittance ≥95%, conductivity ≤300us / cm).

[0024] The fourth step involves purifying concentrate III using a continuous ion exchange device to produce a product liquid. This product liquid can be further purified by evaporation, crystallization, and centrifugation to obtain a high-purity histidine product.

[0025] The following will describe each processing unit involved in this system in conjunction with the above procedures, including: The primary ceramic membrane filtration unit comprises a core structure consisting of a primary reflux pipe A11, a primary feed tank A12, a primary feed pump A13, a primary ceramic membrane separation component A14 with a separation pore size of 0.05–0.2 μm, and a primary dialysis tank A15. The primary reflux pipe A11 connects the concentrate outlet of the primary ceramic membrane separation component A14 to the primary feed tank A12, and a heat exchange device 50 is installed on the primary reflux pipe A11. During operation, histidine fermentation broth with a solid content of 7-8% first enters the primary feed tank A12 for temporary storage. After being pressurized by the primary feed pump A13, it is fed into the primary ceramic membrane separation component A14 for filtration. Suspended solids are retained, forming concentrate I and dialysate I. Concentrate I is returned to the primary feed tank A12 via the primary reflux pipe A11 for recycling, while dialysate I enters the primary dialysis tank A15 via a pipe for temporary storage, providing preliminarily clarified feed for the next stage of processing.

[0026] A secondary nanofiltration membrane decolorization unit is used to receive the previous stage dialysate (i.e., dialysate I) and process it to output dialysate II. The secondary nanofiltration membrane decolorization unit includes a secondary reflux pipeline A21, a secondary feed tank A22, a secondary feed pump A23, a secondary nanofiltration membrane separation component A24 with a molecular weight cutoff of 200-1000 Daltons, and a secondary dialysis tank A25. During operation, the secondary reflux pipeline A21 is connected to the concentrate outlet of the secondary nanofiltration membrane separation component A24 and the secondary feed tank, and a heat exchange device 50 is installed on the secondary reflux pipeline A21. During operation, the feed solution in the primary dialysis tank A15 is piped into the secondary raw material tank A22, and then pushed by the secondary feed pump A23 into the secondary nanofiltration membrane separation component A24 for decolorization. At this time, small molecule pigments and inorganic salts permeate through the membrane to form dialysis solution II, which flows into the secondary dialysis tank A25 through the pipeline. The non-permeable colored macromolecules are returned to the secondary raw material tank A22 as concentrated solution II through the secondary reflux pipeline A21 with heat exchange device 50 for further separation. This process completely replaces traditional activated carbon decolorization with nanofiltration membrane, which can effectively eliminate carbon powder pollution and significantly improve decolorization efficiency.

[0027] The three-stage high-pressure nanofiltration membrane concentration unit is used to receive the previous stage dialysate (i.e., dialysate II) and process it to output dialysate III and concentrate III. The three-stage high-pressure nanofiltration membrane concentration unit includes a three-stage feed tank A32, a three-stage feed pump A33, a three-stage high-pressure nanofiltration membrane module A34, and a three-stage reflux pipeline A31. During operation, the feed solution from the secondary dialysis tank A25 enters the tertiary feed tank A32 via a pipeline. The tertiary high-pressure nanofiltration membrane module A34 has a separation pore size of less than 100 Daltons, an operating pressure of 45–55 bar, and is equipped with a dialysate outlet and a concentrate outlet. The concentrate outlet is connected to the tertiary feed tank A32 via a tertiary reflux pipeline A31, which is equipped with a heat exchanger 50. The dialysate outlet is connected to the tertiary dialysis tank A35. Under high pressure, histidine is retained to form concentrate III, which is returned to the feed tank via the tertiary reflux pipeline A31 with the heat exchanger 50 for continuous concentration, thereby providing a high-concentration feed for the quaternary continuous ion exchange unit. The dialysate III is then fed into the tertiary dialysis tank A35 for storage. This dialysate can be used as recycled water for the entire system to reduce the overall water consumption.

[0028] In this embodiment, the four-stage continuous ion exchange unit is used to receive the high-concentration concentrate output from the three-stage feed tank A32. It achieves precise purification of histidine through the coordinated operation of 30 ion exchange columns. The specific implementation method is as follows: The four-stage continuous ion exchange unit comprises the following functional zones arranged sequentially, with each functional zone connected in an orderly manner by pipelines (the specific pipeline connection method will not be described here). Its functional zones include: Please refer to the following zones: adsorption zone 41, by-product top water zone 42, water washing and regeneration zone 43, regeneration zone 431, water top desorption zone 44, desorption zone 441, product top water zone 45, and washing zone 46. Figure 1 The following is a brief description of the working principle of this four-stage continuous ion exchange unit, based on the numerical designation used in the designation: The adsorption zone 41 is configured to be connected to a three-stage raw material tank A32. The infusion pipeline of the three-stage raw material tank A32 is connected to the first and second adsorption columns in parallel, and then connected in series in parallel groups of the third and fourth adsorption columns, the fifth and sixth adsorption columns, the seventh and eighth adsorption columns, the ninth and tenth adsorption columns, and the eleventh and twelfth adsorption columns. The by-product top water zone 42 is configured to use the product tail liquid containing by-products (from the adsorption zone 41) to push out the residual water in the column and recover it to the water reuse system to reduce water consumption. Specifically, it includes a second reverse column, which is numbered as the thirteenth top water column in the attached figure. The second reverse column is used to inject the product tail liquid flowing out of the adsorption zone in reverse. The water washing and regeneration zone 43 is configured such that the pure water inlet is connected to the fourteenth and fifteenth regeneration columns in series via a pipeline; The regeneration zone 431 is configured such that the regenerant inlet is connected via a pipeline to the sixteenth and fifteenth regeneration columns in parallel, and then connected in series to the seventeenth and eighteenth regeneration columns; The water-top desorption zone 44 is configured such that the pure water inlet is connected via a pipeline to the nineteenth, twentieth, and twenty-first desorption columns connected in series. The desorption zone 441 is configured such that: the desorption liquid inlet is connected to the parallel 22nd, 23rd and 24th desorption columns via a pipeline, and its outlet is connected to the parallel 25th, 26th and 27th desorption columns after merging with the outlet of the 21st desorption column; The product top water zone 45 is configured to include a first reverse column, which is numbered as the 28th top water column in the figure. During operation, the product tail liquid output from the 25th to 27th desorption columns is reversed and fed into the 28th top water column, and the water pushed out is recycled to the water reuse system. The washing zone 46 is configured such that the pure water inlet is connected via a pipeline to the 29th and 30th washing columns connected in series.

[0029] It should be noted that the continuous ion exchange unit used in this invention also includes a drive device, necessary connecting pipes, pump body, valve body, etc. The aforementioned components are all prior art, so they will not be described in detail here.

[0030] The above embodiments are only used to illustrate the technical solutions of this utility model and are not intended to limit it. Although this utility model has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of this utility model without departing from the spirit and scope of the technical solutions of this utility model, and all such modifications and substitutions should be covered within the scope of the claims of this utility model. Technologies, shapes, and structural parts not described in detail in this utility model are all known technologies.

Claims

1. A histidine purification system based on membrane separation and continuous ion exchange technology, characterized in that, The following processing units are connected in series via pipes: A primary ceramic membrane filtration unit is used for solid-liquid separation of histidine fermentation broth. The primary ceramic membrane filtration unit includes a primary ceramic membrane separation component (A14) with a separation pore size of 0.05–0.2 μm. A secondary nanofiltration membrane decolorization unit is used to decolorize the dialysate from a primary ceramic membrane filtration unit. The secondary nanofiltration membrane decolorization unit includes a secondary nanofiltration membrane separation component (A24) with a separation pore size of 200–1000 Daltons. A three-stage high-pressure nanofiltration membrane concentration unit is used to concentrate the dialysate from the two-stage nanofiltration membrane decolorization unit. The three-stage high-pressure nanofiltration membrane concentration unit includes a three-stage high-pressure nanofiltration membrane assembly (A34) with a separation pore size of less than 100 Daltons and an operating pressure of 45–55 bar. The four-stage continuous ion exchange unit is used to purify the concentrate from the three-stage high-pressure nanofiltration membrane concentration unit through ion exchange.

2. The histidine purification system based on membrane separation and continuous ion exchange technology according to claim 1, characterized in that, The primary ceramic membrane filtration unit also includes: Primary feed tank (A12) is used to receive and temporarily store histidine fermentation broth; A primary feed pump (A13) has its inlet connected to a primary raw material tank (A12) and its outlet connected to the inlet of the primary ceramic membrane separation unit (A14). And a primary dialysis tank (A15), connected to the dialysate outlet of the primary ceramic membrane separation assembly (A14).

3. The histidine purification system based on membrane separation and continuous ion exchange technology as described in claim 2, characterized in that, The primary ceramic membrane filtration unit also includes: The primary reflux pipe (A11) connects the concentrate outlet of the primary ceramic membrane separation unit (A14) to the primary feed tank (A12).

4. The histidine purification system based on membrane separation and continuous ion exchange technology according to claim 1, characterized in that, The secondary nanofiltration membrane decolorization unit further includes: The secondary feed tank is used to receive and temporarily store the dialysis fluid from the primary ceramic membrane filtration unit; A secondary feed pump (A23) has its inlet connected to a secondary feed tank and its outlet connected to the inlet of the secondary nanofiltration membrane separation module (A24); The secondary dialysis vessel (A25) is connected to the dialysate outlet of the secondary nanofiltration membrane separation assembly (A24).

5. The histidine purification system based on membrane separation and continuous ion exchange technology according to claim 4, characterized in that, The secondary nanofiltration membrane decolorization unit further includes: The secondary reflux pipeline (A21) connects the concentrate outlet of the secondary nanofiltration membrane separation unit (A24) to the secondary feed tank.

6. The histidine purification system based on membrane separation and continuous ion exchange technology according to claim 1, characterized in that, The three-stage high-pressure nanofiltration membrane concentration unit includes: The three-stage feed tank is used to receive and temporarily store the dialysis solution from the secondary nanofiltration membrane decolorization unit; The three-stage feed pump (A33) has its inlet connected to the three-stage feed tank and its outlet connected to the inlet of the three-stage high-pressure nanofiltration membrane module (A34); The three-stage dialysis vessel (A35) is connected to the dialysate outlet of the three-stage high-pressure nanofiltration membrane module (A34).

7. The histidine purification system based on membrane separation and continuous ion exchange technology according to claim 6, characterized in that, The three-stage high-pressure nanofiltration membrane concentration unit also includes: The third-stage reflux pipeline (A31) connects the concentrate outlet of the third-stage high-pressure nanofiltration membrane module (A34) to the third-stage feed tank.

8. The histidine purification system based on membrane separation and continuous ion exchange technology according to claim 1, characterized in that, The four-stage continuous ion exchange unit includes an adsorption zone (41), a water washing and regeneration zone (43), a regeneration zone (431), a water top desorption zone (44), a desorption zone (441), a product top water zone (45), and a washing zone (46) arranged sequentially. The adsorption zone (41) is used to receive the concentrate output from the three-stage high-pressure nanofiltration membrane concentration unit; The water washing and regeneration zone (43) is used for the injection of pure water; The regeneration zone (431) is used for regenerant injection; The water-top desorption zone (44) is used for injecting pure water; The desorption zone (441) is used for injecting the desorption solution; The product top water zone (45) includes a first reverse column, which is used for reverse injection of the product tail liquid flowing out of the self-desorption zone (441); The washing area (46) is used for the injection of pure water.

9. The histidine purification system based on membrane separation and continuous ion exchange technology as described in claim 8, characterized in that: A by-product top water zone (42) is provided between the adsorption zone (41) and the water washing and regeneration zone (43). The by-product top water zone (42) includes at least one second reverse column, which is used to inject the adsorption tail liquid flowing out of the adsorption zone (41) in the reverse direction.

10. The histidine purification system based on membrane separation and continuous ion exchange technology as described in claim 8, characterized in that: The adsorption zone (41) adopts a multi-level parallel group series topology, which includes at least 3 groups of parallel adsorption column units connected in series.

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