Hyaluronic Acid, Hyaluronan, Uronic Acid, HA, 9004-61-9

Hyaluronic Acid, Hyaluronan, Uronic Acid, HA, 9004-61-9

Hyaluronic Acid 

1. Product Identity

2. Synonyms and Identifiers

Hyaluronic acid is known by various names across different industries and applications:

• Common Names: HA, Hyaluronan, Hyaluronic acid, Uronic acid

• Salt Form Names: Hyaluronic Acid Sodium, HYALURONIC ACID NA-SALT, Sodium Hyaluronate

• Source-Based Names: HYALURONIC ACID HUMAN SODIUM SALT, HYALURONIC ACID, SODIUM SALT, STREPTOCOCCUS SPECIES

• Chemical Identifiers:

  • [BETA-SODIUM-GLUCONATE-(1,3)-BETA-N-ACETYL-D-GLUCOSAMINE-1,4-]N

  • sodium (2S,3S,4R,5R,6R)-3-((2S,3R,5S,6R)-3-acetamido-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)-4,5,6-trihydroxytetrahydro-2H-pyran-2-carboxylate

• InChI: InChI=1/C28H44N2O23/c1-5(33)29-9-18(11(35)7(3-31)47-25(9)46)49-28-17(41)15(39)20(22(53-28)24(44)45)51-26-10(30-6(2)34)19(12(36)8(4-32)48-26)50-27-16(40)13(37)14(38)21(52-27)23(42)43/h7-22,25-28,31-32,35-41,46H,3-4H2,1-2H3,(H,29,33)(H,30,34)(H,42,43)(H,44,45)/t7-,8-,9-,10-,11-,12-,13+,14?,15-,16-,17-,18-,19?,20+,21+,22?,25?,26+,27+,28-/m1/s1

3. Physicochemical Properties

4. Structural Characteristics

Hyaluronic acid is an acidic mucopolysaccharide (glycosaminoglycan). Unlike other mucopolysaccharides, it does not contain sulfur.

• Basic Structure: It is a high molecular weight polymer composed of disaccharide units of D-glucuronic acid and N-acetylglucosamine.

• Linkage: The disaccharide units repeat as (1 → 3)-2-acetylamino-2-deoxy-β-D-glucose-(1 → 4)-O-β-D-glucuronic acid.

• Molecular Weight: Ranges from 100,000 to 10 million Daltons (3 × 10⁵ ~ 4 × 10⁶).

• Hydrolysis: When hydrolyzed, it produces a hexosamine (such as glucosamine) and a uronic acid (such as glucuronic acid).

• Specific Rotation: The specific rotation of its aqueous solution is between -70° and -80°.

5. Viscosity and Stability

The most prominent feature of hyaluronic acid is its high viscosity. The viscosity of the solution can be irreversibly reduced in the following situations:

1. pH Value: When the pH falls below or rises above 7.

2. Enzymes: In the presence of the enzyme hyaluronidase.

3. Reducing Substances: In the presence of cysteine, pyrogallic acid, ascorbic acid (vitamin C), or heavy metal ions.

4. Irradiation: Exposure to ultraviolet (UV) rays or electron beam radiation.

6. Natural Sources and Occurrence

Hyaluronic acid is widely found in nature within various animal tissues:

• Connective tissue

• Umbilical cord

• Skin (abundant in the dermis layer of human skin)

• Human serum

• Cockscomb (one of the richest sources)

• Joint fluid (Synovial fluid)

• Brain

• Cartilage

• Vitreous body of the eye (Vitreous humor)

• Human urine

• Chicken embryo

• Artery and vein walls

In tissues, it is often found combined with proteins and coexists with other mucopolysaccharides.

• In vitreous body and synovial fluid: In dissolved form.

• In cockscomb and umbilical cord: In gel form.

7. Production Methods

Hyaluronic acid is produced using three main methods:

1. Extraction from Animal Tissue (Traditional Method):

• Raw Materials: Cockscomb, bovine vitreous humor, human umbilical cord.

• Process: Tissues are defatted and dehydrated with acetone or ethanol. Extraction is performed with distilled water. Treated with sodium chloride and chloroform. Purified using enzymes like trypsin. High-purity product is obtained using ion exchangers.

• Advantage/Disadvantage: Very low yield (~1%). It is a complex and expensive process, resulting in a high-cost product.

2. Microbial Fermentation (Most Common Modern Method):

• Microorganism: Specially selected strains of Streptococcus zooepidemicus or other Streptococcus/Lactococcus species.

• Process: Fermentation is carried out for 48 hours in a medium containing glucose as a carbon source. After fermentation, mycelia and impurities are removed by filtration. High-purity product is obtained through simple operations like alcohol precipitation.

• Advantage: Low cost. The molecular weight can be tailored as desired.

3. Chemical Synthesis:

• Process: Uses natural enzyme polymerization. Hyaluronic acid derivatives are produced through polysaccharide polymer synthesis, followed by enzymatic treatment to synthesize hyaluronic acid.

• Advantage/Disadvantage: Can significantly reduce costs, but may have structural purity issues.

8. Physiological Functions and Health Benefits

Hyaluronic acid exhibits various important physiological functions in the body due to its unique molecular structure and physicochemical properties:

1. Joint Health:

• It is a vital component of synovial fluid.

• It acts as a lubricant for joints, reducing friction during movement.

• It serves as a shock absorber, protecting joints from impact.

• Used in intra-articular injections (viscosupplementation) for treating osteoarthritis.

2. Skin Health and Anti-Aging Effects:

• Abundantly present in the dermis layer of the skin, it maintains the skin's moisture balance.

• It is recognized as a Natural Moisturizing Factor (NMF) . It can hold up to 500 times its weight in water. A 2% pure hyaluronic acid solution retains 98% of the water.

• It maintains skin elasticity, delays wrinkle formation, and keeps the skin smooth, soft, and supple.

• The amount of hyaluronic acid in the skin decreases with age:

  • At age 20: 100% (reference)

  • At age 30: 65%

  • At age 50: 45%

  • At age 60: 25%

• UV rays break down hyaluronic acid in the skin.

3. Tissue Repair and Wound Healing:

• Provides a suitable environment for cell proliferation and migration.

• Accelerates wound healing and supports tissue regeneration.

• Used in the treatment of burns, frostbite, and wounds.

4. Eye Health:

• Found in the vitreous body of the eye, helping to maintain its shape.

• Used as a visco-surgical agent in eye operations like cataract surgery. It stays in the anterior chamber, maintaining a clear surgical field and protecting tissues.

5. Cellular Functions:

• Regulates the permeability of blood vessel walls.

• Regulates the diffusion and movement of proteins, water, and electrolytes (Ca²⁺, Mg²⁺, K⁺, Na⁺).

• Regulates ion movement on and around the cell surface.

• Has effects on immune cells (macrophages, lymphocytes).

6. Liver and Diagnostics:

• Hyaluronic acid is primarily degraded in the liver. During liver fibrosis, HA synthesis increases, and in cirrhosis, liver function decreases, leading to abnormally high HA levels in the blood. Therefore, blood HA level is used as a highly sensitive and specific biomarker for diagnosing liver fibrosis and cirrhosis.

9. Applications and Uses

Cosmetics and Personal Care (Most Common Use):

• Moisturizer: Used in creams, lotions, masks, serums, and sunscreens as an ideal natural moisturizing factor. It improves skin nutrition, making the skin smooth and soft.

• Anti-Aging Products: In anti-wrinkle creams and serums.

• Hair and Body Products: In shampoos, conditioners, and body lotions.

Medical and Pharmaceutical Applications:

• Ophthalmology (Eye Diseases):

  • To protect the anterior chamber and maintain a clear surgical view during cataract surgery (phacoemulsification).

  • In corneal transplant and retinal detachment surgery.

  • In artificial tears for treating dry eye syndrome.

• Orthopedics and Rheumatology:

  • Intra-articular viscosupplementation injections (e.g., hyaluronic acid injection into the knee joint) for treating osteoarthritis.

• Surgery:

  • As a surgical barrier to prevent adhesions.

  • In wound dressings to accelerate healing.

• Aesthetic and Plastic Surgery:

  • Dermal Filler: Widely used as an injectable filler to smooth wrinkles, add volume to lips, and enhance facial contours (cross-linked hyaluronic acid gel form).

Food Supplements:

• Oral hyaluronic acid supplements (capsules, liquids) are used to support skin, joint, and eye health. When taken orally, it is absorbed from the intestines, enters the bloodstream, and reaches the tissues.

10. Side Effects and Precautions

Hyaluronic acid is generally considered safe, but side effects can occur in some cases:

• Post-Injection Local Reactions: Pain, swelling, redness, warmth, pressure sensation (usually temporary, resolving within a week).

• Allergic Reactions: Urticaria (hives), itching (rare).

• Contraindications:

  • Pregnancy and lactation.

  • Under 18 years of age.

  • Infection or inflammation at the injection site.

  • Known allergy to hyaluronic acid.

  • Patients taking blood thinners (aspirin, NSAIDs) should consult a doctor before injections.

Precautions:

• Injections must be performed under sterile conditions.

• For joint injections, if there is significant inflammation in the joint, injection should be avoided until the inflammation subsides.

• Avoid exposure to high-heat environments (sauna, steam bath) for 2 weeks after injection.

• Do not massage the injection area.

11. Distinguishing Between Genuine and Fake Products

Substances that can be confused with hyaluronic acid in the market: Ormadin, silicone oil, paraffin oil, cellulose, collagen. They can be distinguished with simple tests:

1. Oiliness Test: Squeeze the gel onto white paper. If an oily halo spreads, it is not hyaluronic acid; it could be silicone oil or paraffin oil.

2. Water Test: If a watery halo spreads, it could be hyaluronic acid, ormadin, cellulose, or collagen.

3. Finger Test: Place a small amount of gel on your palm and rub with your finger. After the water evaporates, if the remaining residue contains sand-like crystalline particles, it is cross-linked hyaluronic acid (genuine HA filler).

4. Glass Plate Test: Squeeze the gel onto a glass plate and leave it overnight. After the water evaporates:

   • If "ice crystal" like particles accumulate: Hyaluronic acid.

   • If an opaque crust forms: Ormadin.

   • If a soft, yellowish film forms: Cellulose.

   • If a non-volatile oily residue remains: Silicone oil or paraffin oil.

   • If nothing remains: Non-cross-linked hyaluronic acid.

5. Enzyme Test: Place the suspicious solid particles in a container with hyaluronidase enzyme at 45°C. If the particles dissolve (degrade) within about 2 hours, it is hyaluronic acid. If they do not dissolve, it is definitely not hyaluronic acid.

12. Safety Information

Storage: Store at -20°C in a dry, dark place.