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CN-122012654-A - Efficient hyaluronic acid production method

CN122012654ACN 122012654 ACN122012654 ACN 122012654ACN-122012654-A

Abstract

The invention belongs to the technical field of hyaluronic acid fermentation, and provides a high-efficiency hyaluronic acid production method, which comprises the steps of 1) inoculation, 2) fermentation, 3) filtration and impurity removal and drying. The restriction of high-viscosity fermentation liquor on dissolved oxygen and matrix transmission is relieved by aeration, the purpose of obtaining high-density thalli is achieved, and the synthesis of the hyaluronic acid synthase is induced, so that the capacity of the high-density thalli for generating capsules is recovered, and the purpose of improving the yield of hyaluronic acid is achieved.

Inventors

  • ZHAO JIE
  • WANG FEI
  • YANG XIAOFANG
  • ZHANG XIAOYONG
  • WANG KUIZHI

Assignees

  • 新疆阜丰生物科技有限公司

Dates

Publication Date
20260512
Application Date
20251231

Claims (7)

  1. 1. A high-efficiency hyaluronic acid production method comprises the steps of 1) inoculation, 2) fermentation, 3) filtration and impurity removal and drying.
  2. 2. The method for efficiently producing hyaluronic acid according to claim 1, which is characterized by comprising the following specific steps: step 1), inoculating, namely inoculating streptococcus zooepidemicus ATCC39920 seed solution into a fermentation culture medium according to an inoculum size of 5-10% for fermentation culture; The components of the fermentation medium are 10-15 g/L glucose, 5-8g/L peptone, 1-3 g/L dipotassium phosphate trihydrate, 1-1.5 g/L magnesium sulfate heptahydrate, 0.5-1g/L potassium dihydrogen phosphate, 0.5-1g/L dipotassium phosphate, 50-100mg/L zinc sulfate heptahydrate, 12-15 g/, 5-8g/L yeast extract powder, water as solvent, and adjusting the pH value to 7-7.5 by using a caustic soda solution; step 2) fermentation, in the primary fermentation process, aeration is carried out, the aeration amount is 3-5 times of the volume/h of the culture medium, the glucose solution with the concentration of 25-30g/L is added in an atomized manner, the sodium chloride solution with the concentration of 5-15g/L is added in an atomized manner, and the hyaluronidase solution with the concentration of 0.5-2g/L is added in an atomized manner at regular time; In the later fermentation process, in 8-36h, the aeration amount is 5-8 times of the volume/h of the culture medium, the glucose solution with the concentration of 30-35g/L is added in an atomizing way, and the sodium chloride solution with the concentration of 1-5g/L is added in an atomizing way, so that fermentation liquor is obtained; step 3) filtering to remove impurities, centrifugally filtering the fermentation liquor, taking supernatant, adding clear water with the volume of 1-2 times for dilution, then adsorbing by using active carbon, and filtering by using a resin column; step) drying, concentrating the modified solution, and drying with hot air to obtain hyaluronic acid powder.
  3. 3. The method for efficiently producing hyaluronic acid according to claim 1, wherein the step 2) of fermentation is performed by using an aeration disc, the aeration disc is a sleeved disc, and a pump group and a plurality of atomizing pipelines are connected to a connecting pipeline of the aeration disc at the bottom of the fermentation tank.
  4. 4. The method for efficiently producing hyaluronic acid according to claim 1, wherein the fermentation in the step 2) is performed by aeration, and the aeration holes are 1-2mm fine holes.
  5. 5. The method for efficiently producing hyaluronic acid according to claim 1, wherein the fermentation in the step 2) is performed at a timing of atomizing for 5 to 10 minutes, and atomizing again after 1 to 5 minutes.
  6. 6. The method for efficiently producing hyaluronic acid according to claim 1, wherein the fermentation in the step 2) is performed by ultrasonic atomization.
  7. 7. The method for efficiently producing hyaluronic acid according to claim 1, wherein the pH of the fermentation liquid is controlled to 7.0 by NaOH, and the rotation speed is 200r/min.

Description

Efficient hyaluronic acid production method Technical Field The invention belongs to the technical field of hyaluronic acid preparation, and particularly provides a high-efficiency hyaluronic acid production method. Background Hyaluronic Acid (HA) is a high viscosity, non-sulfated, natural acidic polymeric polysaccharide, also known as Hyaluronic Acid. Hyaluronic acid has various physiological functions such as moisture preservation, lubrication and the like, is widely applied to the fields of foods, medicines and cosmetics at present, and has wide market-scale and bright application prospect. In the conventional process of producing hyaluronic acid by fermentation, the problems of insufficient dissolved oxygen and hindered substrate transfer caused by the increase of the viscosity of fermentation liquid are often faced, and the growth of thalli and the synthesis of hyaluronic acid are affected. In addition, high density cells may lose the ability to produce hyaluronic acid (i.e., capsule) during continued growth, limiting the final yield of hyaluronic acid. The application number is 2024115141222, which discloses a method for improving the fermentation yield of hyaluronic acid, wherein starch sugar and hyaluronidase liquid are fed in different fermentation stages, on one hand, the fed-batch of sugar can prevent the quick generation of viscosity in the fermentation process and reduce the inactivation of strains caused by uneven distribution of too high viscosity alkali liquid, and on the other hand, the hyaluronidase is used for cracking the molecular chain of the hyaluronic acid, reducing the viscosity of the hyaluronic acid fermentation liquid and improving the mass transfer effect of materials in the fermentation process so as to improve the yield. The hyaluronic acid fermentation liquor prepared by the method has high yield and conversion rate, simple process and suitability for large-scale production and application. The viscosity of the hyaluronic acid fermentation liquor is high, fed-batch materials cannot be mixed uniformly rapidly, strain growth, synthesis and the like occur, and a high-efficiency production method of hyaluronic acid is needed at present. Disclosure of Invention The invention provides a high-efficiency production method of hyaluronic acid, which is used for preparing hyaluronic acid based on the method disclosed by the invention, and can be used for remarkably improving the production efficiency of hyaluronic acid. A high-efficiency hyaluronic acid production method comprises the steps of 1) inoculation, 2) fermentation, 3) filtration and impurity removal and drying. The method comprises the following specific steps: step 1), inoculating, namely inoculating streptococcus zooepidemicus ATCC39920 seed solution into a fermentation culture medium according to an inoculum size of 5-10% for fermentation culture; The components of the fermentation medium are 10-15 g/L glucose, 5-8g/L peptone, 1-3 g/L dipotassium phosphate trihydrate, 1-1.5 g/L magnesium sulfate heptahydrate, 0.5-1g/L potassium dihydrogen phosphate, 0.5-1g/L dipotassium phosphate, 50-100mg/L zinc sulfate heptahydrate, 12-15 g/, 5-8g/L yeast extract powder, water as solvent, and adjusting the pH value to 7-7.5 by using a caustic soda solution; step 2) fermentation, in the primary fermentation process, aeration is carried out, the aeration amount is 3-5 times of the volume/h of the culture medium, the glucose solution with the concentration of 25-30g/L is added in an atomized manner, the sodium chloride solution with the concentration of 5-15g/L is added in an atomized manner, and the hyaluronidase solution with the concentration of 0.5-2g/L is added in an atomized manner at regular time; In the later fermentation process, in 8-36h, the aeration amount is 5-8 times of the volume/h of the culture medium, the glucose solution with the concentration of 30-35g/L is added in an atomizing way, and the sodium chloride solution with the concentration of 1-5g/L is added in an atomizing way, so that fermentation liquor is obtained; step 3) filtering to remove impurities, centrifugally filtering the fermentation liquor, taking supernatant, adding clear water with the volume of 1-2 times for dilution, then adsorbing by using active carbon, and filtering by using a resin column; step) drying, concentrating the modified solution, and drying with hot air to obtain hyaluronic acid powder. Further, the fermentation in the step 2) is performed, aeration is performed by adopting an aeration disc, the aeration disc is sleeved with a disc, and a pump group and a plurality of atomizing pipelines are connected to the connection pipeline of the aeration disc at the bottom of the fermentation tank. Further, the fermentation in the step 2) is carried out, and aeration holes are fine holes with the diameter of 1-2 mm. Further, the fermentation in the step 2) is performed, the atomization is stopped for 5-10 minutes, and the atomization is performed ag