1.What is B-HA?

● B-HA is a bioactive fragment of hyaluronic acid (HA) with an average molecular weight of 35 kDa, classified as a low-molecular-weight hyaluronic acid (LMW-HA). It is enzymatically derived from medical-grade high-molecular-weight HA (HMW-HA) using recombinant human sperm acrosomal hyaluronidase PH20 (Patent No. ZL201310325056.X)[1].

2.Definition:

● Low-molecular-weight hyaluronic acid (LMW-HA), capable of penetrating human tissues, prepared through filtration using a 220nm pore membrane;

● A 0.018% (w/v) solution of LMW-HA that interacts with or directly binds to cell membranes.

3.In Vitro Bioactivity:

● Freely permeable through human tissues for molecules under 220nm; [2,3]

● Interacts with or directly binds to cell membranes;

● Inhibits pain-associated calcium ion channels TRPV1 (Transient Receptor Potential Vanilloid 1) and TRPA1 (Transient Receptor Potential Ankyrin 1);

● Facilitates the outward migration of inflammatory cells from gel droplets simulating "inflammatory tissues."

4.In Vivo Bioactivity (Effects in the Human Body):

● Powerful Anti-Inflammatory Effects – Helps reduce inflammation and promote tissue recovery. [2,3]

● Exceptional Tissue Permeability – Easily penetrates tissues, enhancing bioavailability. [2,3]

● Facial Aesthetics & Anti-Aging – Improves skin hydration, elasticity, and overall appearance. [4]

● Accelerated Wound Healing – Supports tissue regeneration and repair. [5]

● Neuropathic Pain Relief – Effective in managing conditions such as herpes zoster. [6]

● Inflammatory Pain Reduction – Alleviates pain in the shoulder, neck, back, and temporomandibular regions. [6,7]

● Cancer Pain Management – Provides relief for pain associated with lung cancer, laryngeal cancer, and other open-organ tumors. [8]

5.Scientific Research Background of B-HA:

The naked mole rat, often called the "ageless wonder," holds the record for the longest lifespan among rodents, living up to 38 years. Remarkably, these unique creatures do not develop cancer or severe diseases, exhibit no significant signs of aging, and have an unusually high tolerance for pain. Additionally, they possess minimal subcutaneous fat tissue, a rare trait among mammals.

Scientific studies have revealed that naked mole rats have ten times the levels of high-molecular-weight hyaluronic acid (HMW-HA) compared to normal mice. This exceptional abundance of HA is believed to be a key factor contributing to their longevity, cancer resistance, and overall health [9-12].

In August 2023, researchers from the University of Rochester, USA, conducted a groundbreaking genetic study in which they introduced HMW-HA synthesizing genes into ordinary mice using gene transfer technology [2]. Their findings provided compelling evidence of HA’s biological significance, demonstrating:

While HA is essential for human health, its natural levels decline with age. In a 75 kg human body, approximately 16 grams of HA is present, with one-third being broken down and resynthesized daily. However, due to its large molecular size, HMW-HA cannot easily penetrate tissues or be effectively absorbed when supplemented, limiting its therapeutic applications.

To overcome these limitations, researchers developed HA35, a bioactive, highly tissue-permeable Low-Molecular-Weight Hyaluronic Acid (LMW-HA). Unlike traditional HMW-HA, HA35 offers superior absorption and enhanced therapeutic potential, unlocking new possibilities for skin rejuvenation, anti-aging, pain management, and inflammation control.

6.The Unique Science Behind B-HA: Molecular Weight and Bioactivity

Low-Molecular-Weight Hyaluronic Acid (LMW-HA): Superior Permeability & Bioactivity

LMW-HA exhibits exceptional permeability in human blood vessels and tissues, effortlessly passing through a 220 nm pore-size membrane without resistance. Unlike conventional HMW-HA, LMW-HA retains the cytological activity of high-molecular-weight hyaluronic acid (HMW-HA) while offering additional benefits:

● Promotes Inflammation Clearance & Lymphatic Circulation – Facilitates the removal and diffusion of inflammation and lymphocytes from affected areas into lymphatic circulation (Patent Application No. CN114848667A).

● Reduces Nitric Oxide Levels – Plays a crucial role in suppressing nitric oxide accumulation, which is linked to inflammation and tissue damage (Patent Application No. CN114146092A).

● Molecular Weight Range: 10–70 kDa.

High-Molecular-Weight Hyaluronic Acid (HMW-HA): Structural Integrity & Localized Activity

HMW-HA, whether in its non-permeable form within human blood vessels and tissues (unable to pass through a 220 nm pore-size membrane) or in a colloidal state, maintains its cytological activity even when diluted and in the absence of tissue structures. However, due to its large molecular size, its ability to penetrate tissues is highly restricted.

● Molecular Weight Range: >1800 kDa.

Why B-HA Stands Out: Unparalleled Bioactivity & Tissue Penetration

Both LMW-HA and HMW-HA exhibit distinct biological activities, particularly in how they interact with and bind to red blood cell surfaces. However, due to its superior tissue permeability, HA35 demonstrates significantly higher bioactivity compared to traditional HMW-HA (Patent Application No. CN111334468A). This breakthrough enables HA35 to deliver deeper, faster, and more effective therapeutic benefits, making it an optimal choice for medical and cosmetic applications.

7.Granted Patents:

● APPLICATION OF LOW MOLECULAR WEIGHT HYALURONIC ACID (LMW-HA) FRAGMENTS (US11839625B2; US11826380B2; US11826381B2);

● APPLICATION OF LOW MOLECULAR WEIGHT HYALURONIC ACID (LMW-HA) FRAGMENTS (CA3049286);

● APPLICATION OF LOW MOLECULAR WEIGHT HYALURONIC ACID (LMW-HA) FRAGMENTS (AU2017255833);

● APPLICATION OF LOW MOLECULAR WEIGHT HYALURONIC ACID (LMW-HA) FRAGMENTS (EP3479830).

Summary: These patents cover the biomedical applications of low-molecular-weight hyaluronic acid (LMW-HA) fragments in pain relief, anti-inflammation, and cosmetic treatments.

8.Patent Application:

● Oral Formulation of Low-Molecular-Weight Hyaluronic Acid and its Application (International PCT Patent Priority Application No. 202411344317).

9.Articles and References: