Hyaluronidase

Background

Hyaluronidase can be classified into animal-derived and recombinant human-derived enzymes based on their source:

Animal-derived hyaluronidase:

Primarily extracted and purified from testicular tissue of animals (such as cattle or sheep). Due to the complexity and variability of the source, it carries risks of allergic reactions, immunogenicity, and even zoonotic infectious diseases.

Recombinant human hyaluronidase:

The human genome encodes six types of hyaluronidases: HYAL-1, HYAL-2, HYAL-3, HYAL-4, HYAL-P1, and PH-20.

PH-20 is a prototype neutral-active enzyme, and it is the most biologically active hyaluronidase in the human body. It is the primary enzyme responsible for degrading HA in vivo and the only one active under neutral conditions (optimal pH 5–7), making it the most suitable for physiological environments.

Hzymes' recombinant hyaluronidase is produced using recombinant DNA technology, with recombinant human hyaluronidase (rHuPH20) expressed in Chinese Hamster Ovary (CHO) cells. It is manufactured with a high-purity preparation process and stringent quality control, resulting in higher purity, superior biological activity, lower endotoxin levels, tighter batch-to-batch consistency, and is free from animal-derived components and exogenous viral contamination.

Product Overview

Hyaluronic acid, a disaccharide unit glycosaminoglycan, is the predominant form of mucopolysaccharide found in the dermis and was initially isolated from bovine vitreous body. It possesses various functions including joint lubrication, osmotic pressure regulation, and promotion of wound healing. Moreover, it finds applications in ophthalmic surgery, arthritis treatment, medical aesthetics, and other fields. Hyaluronic acid is widely distributed within human connective tissues such as interstitium, vitreous body of the eye, and joints. Its exceptional water-retaining capacity and remarkable viscoelasticity make it an effective barrier against fluid flow within the subcutaneous space of the human body.

Hyaluronidase is an endo-glycosidase that catalyzes the hydrolysis of hyaluronic acid into disaccharides or small oligosaccharides. It can be utilized in the human body to temporarily decrease interstitial tissue viscosity, facilitating the absorption of subcutaneous infusion, locally stored exudate, or blood by promoting diffusion. It serves as an exceptional drug diffuser. Moreover, hyaluronic acid can promote the dissipation of local edema and hematoma after surgery or trauma while accelerating the onset time of local anesthesia drugs and reducing associated pain symptoms upon injection. In medical cosmetology, hyaluronic acid is frequently employed as an ideal soft tissue filler for treating wrinkles, depression, atrophy, etc. However, excessive use of hyaluronic acid injections may lead to side effects such as allergic reactions, subcutaneous induration, inflammatory flesh edema, and tissue necrosis caused by vascular embolism. Hyaluronidase can effectively address postoperative complications resulting from hyaluronic acid injections particularly various vascular crises and prevent vascular embolism occurrences. In addition, hyaluronidase can also be used to prepare low molecular weight glycosamine oligosaccharides and degrade animal subcutaneous glycosaminoglycans for leather industry, replacing the lime method in the traditional leather preparation process, which can greatly reduce environmental pollution.

Comparison of Enzymes Powder

Comparison of Enzymes Solution

Applications

1. Subcutaneous Injection

Among FDA-approved administration routes for marketed antibody drugs, subcutaneous injection is the second most common method after intravenous infusion.

Figure 1. Statistics on administration routes of FDA-approved drugs.

Currently, there are four approved antibody drug products and one approved immunoglobulin product.

Table 1. Marketed antibody drugs containing hyaluronidase worldwide [2].

The mechanism of action of recombinant hyaluronidase (rHuPH20) involves locally depolymerizing hyaluronic acid (HA) in the subcutaneous space, facilitating rapid drug dispersion and temporarily removing the barrier to large-volume subcutaneous administration.

Figure 2. Mechanism of action of hyaluronidase [1].

2. Immunotherapy

3. Aesthetic Medicine

Hyaluronidase (rHuPH20) is commonly used to treat complications following hyaluronic acid injection procedures.

Figure 4. Illustration of facial injection with hyaluronidase [3].

4. Assisted Reproduction

Performance Data

In Vivo Bioactivity

Subcutaneous injection of varying doses of Hzymes hyaluronidase showed high in vivo bioactivity across all tested activity units, with different diffusion effects observed 30 minutes after injection.

Comparative studies of recombinant hyaluronidase at different doses showed that Hzymes' hyaluronidase demonstrated superior in vivo diffusion performance 30 minutes post-injection compared to foreign brand H.

Product Stability

Hzymes hyaluronidase powder and solution exhibit high thermal stability.

Hzymes hyaluronidase powder and solution remain stable even after multiple freeze-thaw cycles.

References

[1] Locke, Kenneth Wetal. “ENHANZE® drug delivery technology: a novel approach to subcutaneous administration using recombinant human hyaluronidase PH20. ” Drug delivery vol. 26, 1 (2019): 98-106.
[2] Knowles, Stephen Petal. “Safety of recombinant human hyaluronidase PH20 for subcutaneous drug delivery. ” Expert opinion on drug delivery vol. 18: 11 (2021): 1673-1685.

[3] 付强, 周桂文, 等. 经皮面动脉透明质酸酶注射治疗面部注射美容致血管栓塞的效果观察[J]. 中华整形外科杂志, 2021, 37 (04): 365-370.