Highly efficient production device for hyaluronic acid

Abstract

The utility model relates to hyaluronic acid production technical field, concretely for hyaluronic acid high -efficient production device, hyaluronic acid high -efficient production device, including fermenter, and the fermenter is linked with disc centrifuge through flocculating agent adding jar, and disc centrifuge is linked with membrane filter through primary filter, and membrane filter is linked with vacuum membrane evaporator through purification device, and vacuum membrane evaporator is linked with drying box through pipeline, and the drying box is connected with heat exchanger, and the fermenter is connected with glucose makeup jar, the device is through setting glucose makeup jar, nitrogen source makeup jar and realizes substrate batch flow feeding, and utilizes drying box connected heat exchanger to send the residual heat to glucose makeup jar temperature -controlled coil pipe and nitrogen source makeup jar temperature -controlled coil pipe through temperature -controlled water pipeline, avoids the substrate inhibition and byproduct accumulation in fermenter, improves raw material utilization.

Description

Technical Field

[0001] This utility model relates to the field of hyaluronic acid production technology, specifically to a high-efficiency hyaluronic acid production device. Background Technology

[0002] Hyaluronic acid (HA), also known as hyaluronic acid, is a linear high-molecular-weight polysaccharide composed of repeating units of D-glucuronic acid and N-acetylglucosamine. It is widely used in pharmaceuticals, cosmetics, and health foods. Its production is mainly achieved through a combination of microbial fermentation (such as with Streptococcus and Escherichia coli) and separation and purification processes.

[0003] Existing hyaluronic acid (HA) production facilities suffer from several problems: Traditional processes use a single-feed method, resulting in excessively high initial concentrations of substrates such as glucose in the fermenter, which can easily lead to substrate inhibition (e.g., high glucose concentrations inhibit bacterial metabolic activity). Simultaneously, the accumulation of byproducts (such as lactic acid and acetic acid) hinders bacterial growth, causing raw material waste (glucose utilization rate less than 60%) and extended production cycles (fermentation time increased by 20%-30%). Direct centrifugation of the fermentation broth results in the mixing of bacteria, impurities, and high-viscosity HA, prolonging centrifugation time (increasing single centrifugation time by more than 30 minutes) and causing severe equipment wear. Single filters using fixed membranes quickly clog the filter pores during filtration, requiring frequent shutdowns for cleaning, reducing filtration throughput by up to 50%, and causing a yield loss (approximately 5%-8%) due to HA adsorption onto the membrane. Utility Model Content

[0004] In view of the shortcomings of the prior art, the purpose of this utility model is to provide a high-efficiency hyaluronic acid production device that significantly improves production efficiency and raw material utilization through precise feed control and multi-stage separation optimization.

[0005] This utility model is achieved using the following technical solution:

[0006] The aforementioned high-efficiency hyaluronic acid production device includes a fermenter, which is connected to a disc centrifuge via a flocculant addition tank. The disc centrifuge is connected to a membrane filter via a primary filter. The membrane filter is connected to a vacuum membrane evaporator via a purification device. The vacuum membrane evaporator is connected to a drying chamber via a pipeline. A heat exchanger is connected to the drying chamber. A glucose replenishment tank is connected to the fermenter.

[0007] Feed-on fermentation avoids substrate inhibition, increasing fermentation intensity to 1.2 g / (L·h) (compared to approximately 0.8 g / (L·h) in traditional processes); the sampling port facilitates real-time monitoring of fermentation parameters, improving process stability. The high-speed rotating drum in the disc centrifuge (speed up to 15000 r / min) achieves a separation factor ≥10000. It can efficiently separate bacterial cells from HA solution, with solid-liquid separation efficiency three times higher than traditional centrifuges; pretreatment reduces the load on subsequent filtration, shortening the overall separation time by 40%.

[0008] The glucose replenishment tank is equipped with an internal stirring paddle, and a temperature control coil for the glucose replenishment tank is located on the outside of the stirring paddle. The fermentation tank is equipped with a sampling port.

[0009] The fermenter is connected to a nitrogen source replenishment tank, and the nitrogen source replenishment tank is equipped with a nitrogen source replenishment tank temperature control coil inside.

[0010] The primary filter contains a filter screen. The disc centrifuge is connected to the primary filter via a pipe located below the filter screen, while the membrane filter is connected to the primary filter above the filter screen. The primary filter utilizes fluid kinetic energy to reduce impurity accumulation on the filter screen, increasing the filtration flux by 60% compared to traditional top-in, bottom-out filters.

[0011] The primary filter is connected to a secondary membrane processor, and the connection between the secondary membrane processor and the primary filter is located below the filter screen. The membrane filter is connected to a backwashing pipe, and the vacuum membrane evaporator is connected to a vacuum pump.

[0012] The heat exchanger is connected to the temperature control coil of the glucose replenishment tank via a temperature-controlled water pipe, and a valve is provided at the connection. The heat exchanger is also connected to the temperature control coil of the nitrogen source replenishment tank via a temperature-controlled water pipe, and a valve is provided at the connection. The heat exchanger is equipped with a temperature-controlled water inlet pipe and a gas phase outlet pipe.

[0013] The working principle of this utility model is as follows:

[0014] Fermentation stage: The culture medium (containing yeast extract and inorganic salts) is added to the fermenter, sterilized, and then inoculated with the inoculum. The temperature is maintained at 35±1℃, pH 6.8-7.2, and dissolved oxygen saturation at 20%-30%.

[0015] After 6-8 hours of fermentation, 50% glucose solution is added at a rate of 5-10 L / h through the glucose replenishment tank, while ammonium sulfate solution is added through the nitrogen source replenishment tank to maintain a carbon-nitrogen ratio (C / N) of 10-15:1.

[0016] During the feeding process, the bacterial cell concentration (OD600) and HA yield were monitored through the sampling port.

[0017] After fermentation is complete, 0.1%-0.3% polyacrylamide (PAM) is added to the tank as a flocculant to promote cell aggregation.

[0018] Centrifugation: After flocculation, the fermentation broth is pumped into a disc centrifuge at a speed of 8000-12000 r / min to separate the bacterial residue (solid content ≥20%). The supernatant enters the primary filter.

[0019] Primary filtration: The supernatant enters from the bottom of the primary filter, and fine impurities are trapped by the filter screen (pore size 10-20μm). The filtrate flows into the membrane filter from the top, and the filtration pressure is ≤0.1MPa.

[0020] Membrane filtration: Ultrafiltration membrane (molecular weight cutoff 50kDa) is used, operating pressure 0.2-0.3MPa, temperature ≤40℃, and the filtrate transmittance ≥95% is allowed to enter the purification device.

[0021] Purification: The filtrate is passed through an ion exchange resin column (DEAE-cellulose) to remove proteins and nucleic acids. The eluent is concentrated to a HA concentration of 10%-15% by a vacuum membrane evaporator at 40-50℃ and a vacuum degree ≤-0.08MPa.

[0022] Drying: The concentrate is pumped into a drying chamber and dried under low temperature vacuum (temperature 50-60℃, vacuum degree ≤-0.09MPa) for 4-6 hours to finally obtain HA powder (moisture content ≤5%).

[0023] Compared with the prior art, the beneficial effects of this utility model are:

[0024] This utility model relates to a high-efficiency hyaluronic acid production device. By setting up glucose replenishment tanks and nitrogen source replenishment tanks, the substrate is added in batches. The waste heat is transferred to the temperature control coils of the glucose replenishment tank and the nitrogen source replenishment tank via a heat exchanger connected to the drying box and temperature control water pipes. This avoids substrate inhibition and by-product accumulation in the fermentation tank and improves raw material utilization. Through the three-stage separation of flocculant addition tank, disc centrifuge, primary filter, and membrane filter, as well as the backwashing pipeline design of the membrane filter, the centrifugation time is shortened, the filtration efficiency is improved, and the filter membrane clogging is reduced, which greatly improves the production efficiency. Attached Figure Description

[0025] Figure 1 This is a schematic diagram of the structure of the high-efficiency hyaluronic acid production device of this utility model;

[0026] In the diagram: 1. Fermentation tank; 2. Disc centrifuge; 3. Primary filter; 4. Membrane filter; 5. Purification unit; 6. Vacuum membrane evaporator; 7. Drying oven; 8. Glucose replenishment tank; 9. Nitrogen source replenishment tank; 10. Flocculant addition tank; 11. Secondary membrane processor; 12. Vacuum pump; 13. Heat exchanger; 14. Temperature control coil of glucose replenishment tank; 15. Temperature control coil of nitrogen source replenishment tank; 16. Sampling port; 17. Filter screen; 18. Backwashing pipe; 19. Temperature-controlled water pipe; 20. Temperature-controlled water inlet pipe to heat exchanger; 21. Gas phase outlet pipe to heat exchanger. Detailed Implementation

[0027] To make the objectives and technical solutions of this utility model clearer, the present utility model will be further described in detail below with reference to the accompanying drawings.

[0028] Example 1

[0029] like Figure 1 As shown, the high-efficiency hyaluronic acid production device includes a fermenter 1. The fermenter 1 is connected to a disc centrifuge 2 via a flocculant addition tank 10. The disc centrifuge 2 is connected to a membrane filter 4 via a primary filter 3. The membrane filter 4 is connected to a vacuum membrane evaporator 6 via a purification device 5. The vacuum membrane evaporator 6 is connected to a drying oven 7 via a pipe. A heat exchanger 13 is connected to the drying oven 7. A glucose replenishment tank 8 is connected to the fermenter 1. The glucose replenishment tank 8 has a stirring paddle inside, and a temperature control coil 14 is located outside the stirring paddle. The fermenter 1 has a sampling port 16. A nitrogen source replenishment tank 9 is connected to the fermenter 1, and a temperature control coil 15 is located inside the nitrogen source replenishment tank. The primary filter 3 has a filter screen 17 inside. The connection point between the disc centrifuge 2 and the primary filter 3 is located below the filter screen 17, and the connection point between the membrane filter 4 and the primary filter 3 is located above the filter screen 17. A secondary membrane processor 11 is connected to the primary filter 3. The connection between the secondary membrane processor 11 and the primary filter 3 is located below the filter screen 17. A backwashing pipe 18 is connected to the membrane filter 4, and a vacuum pump 12 is connected to the vacuum membrane evaporator 6. The membrane filter 4 is equipped with a backwashing pipe 18, which can be connected to clean water or acid / alkali solutions for online cleaning. The backwashing cycle is extended from once per batch in the traditional process to once every three batches. The heat exchanger 13 is connected to the temperature control coil 14 of the glucose replenishment tank via a temperature control water pipe 19, and a valve is installed at the connection. The heat exchanger 13 is also connected to the temperature control coil 15 of the nitrogen source replenishment tank via a temperature control water pipe 19, and a valve is installed at the connection. The heat exchanger 13 is equipped with a temperature control water inlet pipe 20 and a gas phase outlet pipe 21.

[0030] The above-mentioned high-efficiency hyaluronic acid production device includes the following steps during operation:

[0031] (1) During fermentation, after the fermentation tank 1 is inoculated with bacteria, the substrate is added in batches to the glucose replenishment tank 8 and the nitrogen source replenishment tank 9. After fermentation is completed, flocculant is added through the flocculant addition tank 10. (2) After the fermentation liquid is separated by the disc centrifuge 2, it is filtered through the primary filter 3 (bottom feed, top discharge) and the membrane filter 4 in sequence. The filtrate enters the purification device 5 for purification. After purification, the liquid is concentrated by the vacuum membrane evaporator 6. The concentrated liquid is transported to the drying box 7 through the pipeline for drying. The residual heat generated by the drying box 7 is used to control the temperature of the glucose replenishment tank 8 and the nitrogen source replenishment tank 9 through the heat exchanger 13 and the temperature control water pipeline 19, and finally the hyaluronic acid product is obtained.

Claims

1. A high-efficiency hyaluronic acid production device, characterized in that, The fermenter (1) is connected to a disc centrifuge (2) via a flocculant addition tank (10). The disc centrifuge (2) is connected to a membrane filter (4) via a primary filter (3). The membrane filter (4) is connected to a vacuum membrane evaporator (6) via a purification device (5). The vacuum membrane evaporator (6) is connected to a drying oven (7) via a pipe. A heat exchanger (13) is connected to the drying oven (7). A glucose replenishment tank (8) is connected to the fermenter (1).

2. The high-efficiency hyaluronic acid production apparatus according to claim 1, characterized in that, The glucose replenishment tank (8) is equipped with a stirring paddle inside, and a glucose replenishment tank temperature control coil (14) is provided on the outside of the stirring paddle. The fermentation tank (1) is equipped with a sampling port (16).

3. The high-efficiency hyaluronic acid production apparatus according to claim 2, characterized in that, The fermenter (1) is connected to a nitrogen source replenishment tank (9), and the nitrogen source replenishment tank (9) is equipped with a nitrogen source replenishment tank temperature control coil (15).

4. The high-efficiency hyaluronic acid production apparatus according to claim 1, characterized in that, The primary filter (3) is equipped with a filter screen (17) inside. The connection between the disc centrifuge (2) and the primary filter (3) is located below the filter screen (17) through a pipe. The connection between the membrane filter (4) and the primary filter (3) is located above the filter screen (17).

5. The high-efficiency hyaluronic acid production apparatus according to claim 4, characterized in that, The primary filter (3) is connected to a secondary membrane processor (11), and the connection between the secondary membrane processor (11) and the primary filter (3) is located below the filter screen (17). The membrane filter (4) is connected to a backwash pipe (18), and the vacuum membrane evaporator (6) is connected to a vacuum pump (12).

6. The high-efficiency hyaluronic acid production apparatus according to claim 3, characterized in that, The heat exchanger (13) is connected to the temperature control coil (14) of the glucose replenishment tank via a temperature control water pipe (19), and a valve is provided at the connection. The heat exchanger (13) is connected to the temperature control coil (15) of the nitrogen source replenishment tank via a temperature control water pipe (19), and a valve is provided at the connection. The heat exchanger (13) is provided with a temperature control water inlet pipe (20) and a gas phase outlet pipe (21).

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