How is sodium hyaluronate produced

In today’s beauty care and healthcare fields, “hyaluronic acid” is undoubtedly a star ingredient. It is renowned for its outstanding water-locking and moisturizing ability and is hailed as a “natural moisturizing factor”. Among the skin care products, eye drops and even medical aesthetic injections we use daily, the more common one is its stable form – sodium hyaluronate. The wide application of sodium hyaluronate is the result of decades of iterative upgrades in its production technology. Today, the production of sodium hyaluronate has formed a pattern of “traditional extraction” and “modern biological fermentation” running in parallel. Different technical paths have their own characteristics and jointly support a market demand of hundreds of billions of yuan.

At the beginning of discovery: The accident of science

The story of sodium hyaluronate began in 1934. Karl Meyer, an ophthalmology professor at Columbia University in the United States, and his assistant John Palmer have for the first time isolated a new type of polysaccharide from the vitreous body of bovine eyes. This substance has an extremely strong hygroscopicity and is named “Hyaluronic Acid” (hyaluronic acid), which is derived from the Greek words “hyalos” (vitreous body) and “uronic acid” (uronic acid). Although Meyer was aware of its unique viscoelasticity at that time, due to technical limitations, this discovery did not immediately cause a sensation.

In the following decades, the extraction of hyaluronic acid mainly relied on animal tissues (such as cockscombs and cow eyes). Its core raw materials mainly come from chicken combs, bovine vitreous bodies and shark cartilage. Among them, chicken combs were once the most mainstream source of raw materials due to their relatively high sodium hyaluronate content (about 0.3%-0.8%). Although this method can obtain natural substances, it has obvious limitations: the source of raw materials is limited, the extraction process is complex, the purity is difficult to guarantee, and there is a potential risk of the spread of animal-derived diseases. The high cost and limited production volume made sodium hyaluronate only applicable to a few high-end medical fields at that time and unable to enter the homes of ordinary people.

Modern microbial fermentation methods: safe, efficient and sustainable

To overcome the various drawbacks of animal extraction, the scientific and technological community has found a better solution – microbial fermentation method. This technology is hailed as a milestone in the production of sodium hyaluronate. Currently, over 99% of the world’s sodium hyaluronate is produced by this method.

The core process is similar to “wine-making”, but what is produced is the sodium hyaluronate we need:

Step 1: Strain selection and cultivation

Scientists have screened out a non-pathogenic and safe Streptococcus equis in the laboratory. This kind of bacteria is born with the ability to synthesize hyaluronic acid. Through modern biotechnology to optimize and domesticate it, a “super engineered strain” capable of efficiently and stably producing hyaluronic acid has been cultivated. Then, the strains are activated and cultured in the laboratory. Once the vitality of the strains meets the standards, they are transferred to the fermentation tank for large-scale production.

Step 2: Fermentation “Brewing”

These carefully selected strains are put into huge sterile fermentation tanks to provide them with a meticulously formulated “nutritious meal” – including glucose, yeast powder, peptone, etc. Under constant temperature, pH value and ventilation conditions, these microorganisms will grow and reproduce rapidly, and like silkworms spinning silk, they will convert the sugar they consume into transparent hyaluronic acid and secrete it into the culture medium. This process usually lasts for dozens of hours.

Step 3: Separation and purification

After the fermentation is completed, a tank of complex fermentation liquid is obtained. The next key step is to “rinse” out the hyaluronic acid from it. Through a series of sophisticated technologies, such as:

1)Inactivation and filtration: Firstly, kill and remove the bacteria.

2)recipitation and extraction: Add alcohol or other precipitants to precipitate hyaluronic acid from the liquid, forming white fibrous precipitates.

3)Purification and transformation: After multiple processes of dissolution, precipitation, filtration, washing and chromatography, impurities, endotoxins and proteins are removed, and finally high-purity hyaluronic acid is obtained. It is then converted into more stable sodium hyaluronate through neutralization reaction.

Step 4: Drying and finished product

The purified sodium hyaluronate paste will be sent to the drying equipment to remove moisture and finally ground into fine white powder. These powders form the raw material basis for the cosmetics, food and pharmaceutical industries.

Why is microbial fermentation the preferred method in the industry?

Extremely high safety: It completely eliminates the risk of animal-derived diseases, and the production process takes place in a closed and sterile environment, ensuring high product purity.

Outstanding controllability: By adjusting the fermentation conditions (such as nutrition, temperature, and stirring speed), the molecular weight of the produced sodium hyaluronate can be precisely controlled. This means that a wide range of products can be produced, from low-molecular-weight (easily permeable) to super-large-molecular-weight (highly effective surface film-forming), to meet diverse application requirements.

Scale and sustainability: Unrestricted by seasons and animal raw materials, with a wide range of raw material sources (mainly carbohydrates), it can achieve large-scale and low-cost production, meeting the growing demands of the global market. It is an environmentally friendly production method.

Exploration of Emerging Technologies: Chemical Synthesis and Enzyme Catalysis, Opening up the Space for Future imagination

In addition to the two mainstream methods mentioned above, research institutions are actively exploring more efficient production technologies.

Among them, the chemical synthesis method involves artificially synthesizing the repeating units of sodium hyaluronate (D-glucuronic acid and N-acetylglucosamine), and then forming long-chain molecules through polymerization reactions. This method can precisely control the molecular structure and completely break away from the dependence on biological raw materials. However, due to the complex synthesis steps and high cost, it has not yet been applied industrially.

Another direction is the enzymatic catalysis method: using specific enzymes (such as hyaluronidase) to synthesize sodium hyaluronate, which combines the high efficiency of the fermentation method with the precision of the chemical synthesis method. The small-scale production of sodium hyaluronate through enzyme catalytic technology makes the molecular weight distribution of sodium hyaluronate more uniform, and it is expected to become one of the mainstream technologies in the future.

Conclusion

The production history of sodium hyaluronate, from the extraction of expensive cockscombs to the “intelligent manufacturing” of efficient fermentation tanks, is a microcosm of the progress in biotechnology. It is precisely the innovation of this technology that has transformed the once “noble ingredients” into everyday items within our reach today, continuously empowering the health and beauty of consumers around the world. In the future, with the further development of synthetic biology technology, we are expected to witness the emergence of sodium hyaluronate products with superior performance and wider applications.

Renew is a professional factory that produces sodium hyaluronate. We have fresh stock of sodium hyaluronate and support free samples. If you have any requirements for sodium hyaluronate raw materials, please feel free to contact us at any time.