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

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

HYALURONIC ACID (HA)

SECTION 1: PRODUCT IDENTITY AND CHEMICAL IDENTIFICATION

Parameter Information
Product Name Hyaluronic Acid
Chemical Name Hyaluronan
Synonyms (Turkish) Hyaluronik Asit, Hyaluronan, HA, Üronik Asit, Cam Şekeri Karbon Asidi
Synonyms (English) Hyaluronic Acid, Hyaluronan, HA, Uronic Acid
CAS Number 9004-61-9
EC Number (EINECS) 232-678-0
Molecular Formula C₁₄H₂₂NNaO₁₁ (for sodium salt)
Molecular Weight 403.31 g/mol (monomer unit); 100,000 – 10,000,000 Da (polymer)
Chemical Class Glycosaminoglycan (GAG); Mucopolysaccharide
Source Animal tissue (rooster comb, umbilical cord) or microbial fermentation (Streptococcus zooepidemicus)
Appearance White amorphous solid, lyophilized powder
Odor Odorless
Taste Tasteless
Solubility Soluble in water; insoluble in organic solvents

SECTION 2: CHEMICAL STRUCTURE

Structure Description:

    —[D-Glucuronic Acid — N-Acetylglucosamine]—
                   |
                   n

    Hyaluronic Acid
    (C₁₄H₂₁NO₁₁)ₙ

Simplified Structure:

    HOOC—(C₆H₁₀O₇)—O—(C₆H₁₁NO₅)—
                       |
                       n

    Hyaluronic Acid
    Linear polymer chain of repeating disaccharide units
Parameter Description
Molecular Formula (Monomer) C₁₄H₂₁NO₁₁
Molecular Formula (Sodium Salt) C₁₄H₂₂NNaO₁₁
Molecular Weight 100,000 – 10,000,000 Da (polymer)
Chemical Class Glycosaminoglycan (GAG); Acid mucopolysaccharide
Repeating Unit D-glucuronic acid + N-acetylglucosamine
Glycosidic Bonds β-(1→3) and β-(1→4)
Sulfur Content None (unlike other GAGs)
Functional Groups Carboxylic acid (-COOH), hydroxyl (-OH), acetamide (-NHCOCH₃)
SMILES CC(=O)NC1C(C(C(OC1OC2C(C(C(C(O2)C(=O)O)O)O)O)CO)O)O
InChI InChI=1S/C14H21NO11/c1-4(17)15-7-9(20)8(19)6(3-16)25-13(7)26-14-10(21)11(22)12(23)5(2-18)24-14/h5-14,16,18-23H,2-3H2,1H3,(H,15,17)
InChI Key None provided
Specific Rotation [α]D²⁰ -70° to -80° (aqueous solution)

SECTION 3: PHYSICAL AND CHEMICAL PROPERTIES

Property Value Test Method / Note
Appearance White amorphous solid, lyophilized powder Visual
Odor Odorless Olfactometric
Taste Tasteless Sensory
Molecular Weight Variable (100,000 – 10,000,000 Da) GPC / SEC
Density ~1.78 g/cm³ -
Boiling Point 1274.4°C (at 760 mmHg) -
Flash Point 724.5°C -
Refractive Index 1.666 -
Vapor Pressure 0 mmHg (at 25°C) -
Water Solubility Soluble (5 mg/mL, clear solution) General Method
Organic Solvent Solubility Insoluble General Method
Specific Rotation [α]D²⁰ -70° to -80° Polarimetry
Hygroscopicity High (absorbs moisture) -
pH (1% Solution) 5.5 – 7.5 pH Meter
Viscosity High (molecular weight dependent) Viscometer
Water Retention Capacity Up to 500 times its own weight -

SECTION 4: MOLECULAR WEIGHT CLASSES

Class Molecular Weight Source Application
High Molecular Weight HA >1,000,000 Da Rooster comb, fermentation Intra-articular injections, viscosupplementation
Medium Molecular Weight HA 500,000 – 1,000,000 Da Fermentation Wound healing, dermal fillers
Low Molecular Weight HA 50,000 – 500,000 Da Fermentation Cosmetics, moisturizers
Very Low Molecular Weight HA 10,000 – 50,000 Da Enzymatic degradation Transdermal applications, anti-aging
Oligomer HA <10,000 Da Enzymatic hydrolysis Anti-inflammatory, anti-aging
Cross-linked HA Variable Chemical cross-linking Dermal fillers, long-lasting products

SECTION 5: NATURAL SOURCES

Source Location HA Concentration Notes
Rooster Comb (Cockscomb) Chicken comb Highest Traditional extraction source
Umbilical Cord Human, animal High Gel form
Vitreous Humor Eye High Dissolved form
Synovial Fluid Joints High Dissolved form
Skin (Dermis) Human, animal High In connective tissue
Human Serum Blood Low Dissolved form
Cartilage Joints Moderate In connective tissue
Brain Nervous system Low -
Chicken Embryo Egg Low -
Artery/Vein Walls Circulatory Low -

SECTION 6: PRODUCTION METHODS

Method Description Advantages Disadvantages
Animal Tissue Extraction Extraction from rooster comb, umbilical cord or bovine vitreous humor with acetone/ethanol degreasing, water extraction, enzymatic purification Traditional, high purity Low yield (~1%), complex, expensive, animal-derived
Microbial Fermentation Fermentation with Streptococcus zooepidemicus or Lactococcus species in glucose-containing medium for 48 hours, filtration, alcohol precipitation Low cost, high yield, controllable MW, no animal source Bacterial endotoxin risk, purification required
Chemical Synthesis Polysaccharide synthesis via natural enzymatic polymerization, followed by enzymatic processing Low cost Structural purity issues

SECTION 7: PHYSIOLOGICAL FUNCTIONS

Function Description
Joint Lubrication Key component of synovial fluid; reduces friction during movement, acts as shock absorber
Natural Moisturizer (NMF) Can hold up to 500 times its weight in water; maintains skin moisture balance
Tissue Repair Provides suitable environment for cell proliferation and migration; accelerates wound healing
Eye Health Maintains eye shape in vitreous humor; viscoelastic agent in cataract surgery
Intracellular Ion Regulation Regulates diffusion and movement of proteins, water, and electrolytes (Ca²⁺, Mg²⁺, K⁺, Na⁺)
Immune Regulation Affects macrophages and lymphocytes
Biomarker Used in diagnosis of liver fibrosis and cirrhosis (blood HA level)
Anti-inflammatory Low molecular weight HA forms exhibit anti-inflammatory effects

SECTION 8: AGE-RELATED DECLINE

Age Skin HA Level Notes
20 years 100% Reference level
30 years 65% Significant decrease begins
50 years 45% Wrinkles become prominent
60 years 25% Skin elasticity significantly reduced

SECTION 9: APPLICATIONS AND USAGE

Industry Application Description
Cosmetics & Personal Care Moisturizing creams, lotions Natural moisturizing factor; hydrates and smooths skin
  Anti-aging products Anti-wrinkle serums, creams
  Hair and body products Shampoos, conditioners, body lotions
Medical & Pharmaceutical Ophthalmology Cataract surgery, corneal transplant, dry eye treatment (artificial tears)
  Orthopedics & Rheumatology Intra-articular viscosupplementation injections for osteoarthritis
  Surgery Anti-adhesion barriers, wound dressings
Aesthetic & Plastic Surgery Dermal fillers Facial wrinkles, lip augmentation, facial contouring (cross-linked HA)
Food Supplements Oral HA supplements Capsules, liquid form; supports skin, joint and eye health
Veterinary Joint treatments Osteoarthritis treatment in animals

SECTION 10: QUALITY SPECIFICATIONS

Parameter Specification (Cosmetic) Specification (Pharmaceutical) Test Method
Appearance White amorphous powder White amorphous powder Visual
Assay (HA) ≥95.0% ≥98.0% HPLC / Enzymatic
Molecular Weight Variable (customer specific) Variable (customer specific) GPC / SEC
Moisture Content ≤10.0% ≤10.0% Karl Fischer
Protein Content ≤0.1% ≤0.05% Bradford / Kjeldahl
pH (1% Solution) 5.5 – 7.5 5.5 – 7.5 pH Meter
Viscosity (1% Solution) Variable (MW dependent) Variable (MW dependent) Viscometer
Heavy Metals (Pb) ≤10 ppm ≤5 ppm ICP-MS
Arsenic (As) ≤2 ppm ≤1 ppm ICP-MS
Lead (Pb) ≤2 ppm ≤1 ppm ICP-MS
Endotoxin ≤5 EU/mg ≤0.5 EU/mg LAL Test
Microbiological Purity TAMC ≤10² CFU/g TAMC ≤10¹ CFU/g USP <61>
E. coli Negative Negative USP <62>
Salmonella spp. Negative Negative USP <62>
S. aureus Negative Negative USP <62>
P. aeruginosa Negative Negative USP <62>

SECTION 11: SAFETY AND TOXICOLOGICAL PROFILE

Parameter Value / Description
GHS Classification Generally not classified as hazardous substance
Signal Word None (not hazardous)
Hazard Pictograms None
Acute Oral Toxicity (LD50, Rat) >5,000 mg/kg (very low toxicity)
Skin Irritation Not irritant
Eye Irritation Mild irritant (mechanical)
Skin Sensitization Does not cause sensitization
Carcinogenicity Not classified as carcinogenic
Mutagenicity Not mutagenic
Reproductive Toxicity No reproductive toxicity
Target Organs Skin, eyes
RTECS MT7250000
WGK Germany 3 (Water hazard class - high risk)
TSCA Status Yes (Listed)
FLUKA F Codes 3-10
Side Effects (Injection) Pain, swelling, redness (temporary)
Contraindications Pregnancy, lactation, under 18, infection, HA allergy

SECTION 12: GHS CLASSIFICATION AND LABELING

GHS Classification (in accordance with 1272/2008/EC):

Hazard Class Category H-Statement
Generally not classified as hazardous substance
Skin Irritation Category 2 (optional) H315
Eye Irritation Category 2 (optional) H319

Signal Word: None (Not classified as hazardous) or Warning (optional)

Hazard Pictograms: None (generally) or GHS07 (Exclamation mark)

Safety Phrases:

  • S22: Do not breathe dust.

  • S24/25: Avoid contact with skin and eyes.

NFPA 704 Hazard Classification:

Health Flammability Reactivity Special
0 0 0 -
(Minimal health hazard) (Non-combustible) (Stable) (None)

SECTION 13: PRECAUTIONARY STATEMENTS (P-CODES)

Code Statement
P261 Avoid breathing dust/fume/gas
P264 Wash hands thoroughly after handling
P271 Use only outdoors or in a well-ventilated area
P280 Wear protective gloves/protective clothing/eye protection/face protection
P302+P352 IF ON SKIN: Wash with plenty of soap and water
P304+P340 IF INHALED: Remove person to fresh air and keep comfortable for breathing
P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes
P332+P313 If skin irritation occurs: Get medical advice/attention
P337+P313 If eye irritation persists: Get medical advice/attention
P403+P233 Store in a well-ventilated place. Keep container tightly closed
P501 Dispose of contents/container in accordance with local/regional/national/international regulations

SECTION 14: FIRST AID MEASURES

Route of Exposure Action
Inhalation If inhaled as powder, move to fresh air. Seek medical attention if respiratory symptoms persist.
Skin Contact Wash with plenty of soap and water. Seek medical attention if irritation develops.
Eye Contact Rinse thoroughly with plenty of water for at least 15 minutes. Keep eyelids open. Seek medical attention if irritation persists.
Ingestion Rinse mouth with water. Do NOT induce vomiting. Seek medical attention.

SECTION 15: STORAGE AND SHELF LIFE

Parameter Information
Storage Conditions Store at -20°C in a dry, dark place in tightly closed containers.
Temperature Limits -20°C (recommended); -5°C to +5°C (acceptable)
Humidity Low humidity environment (hygroscopic)
Light Protect from light (photodegradation)
Container Requirements Tightly closed, moisture-resistant containers
Shelf Life 24-36 months (under proper storage conditions)
Signs of Degradation Caking, color change, viscosity loss

SECTION 16: PACKAGING OPTIONS

Packaging Type Quantity / Capacity Material
Aluminum Foil Bag 1 g, 5 g, 10 g, 100 g, 1 kg Aluminum / PE
HDPE Drum 5 kg, 10 kg, 25 kg HDPE
Glass Bottle (Amber) 1 g, 5 g, 10 g, 50 g, 100 g Amber glass
IBC Container 500 kg, 1000 kg HDPE

SECTION 17: TRANSPORTATION INFORMATION

Parameter Information
UN Number Not applicable (not classified as dangerous substance)
Hazard Class Not applicable
ADR/RID Not classified as dangerous goods
IMDG Code Not marine pollutant
IATA (Air) Not classified as dangerous goods; can be transported by air
Transport Temperature -20°C (cold chain) or refrigerated

SECTION 18: REGULATORY STATUS

Region / Authority Status
USA (FDA) Approved as cosmetic ingredient; Approved as medical device (dermal fillers)
European Union (EC) Approved as cosmetic ingredient
Turkey Approved as cosmetic, pharmaceutical and food supplement ingredient
ECHA (REACH) Registered substance
TSCA (USA) Listed
California (Prop 65) Not listed
Halal Yes (fermentation-derived)
Kosher Yes (with certification)
Vegan Yes (fermentation-derived)

SECTION 19: OTHER NAMES AND SYNONYMS

Type Name
Turkish Names Hialüronik Asit, Hyaluronan, HA, Üronik Asit, Cam Şekeri Karbon Asidi
English Names Hyaluronic Acid, Hyaluronan, HA, Uronic Acid
Salt Form Sodium Hyaluronate, Hyaluronic Acid Sodium
INCI Name Hyaluronic Acid, Sodium Hyaluronate
Trade Marks Restylane, Juvederm, Hyalgan, Synvisc, Hyaluronic Acid (bulk)
CAS Number 9004-61-9
EC Number 232-678-0
RTECS MT7250000

SECTION 20: CRITICAL WARNINGS AND BEST PRACTICES

CRITICAL WARNINGS:

  1. Hygroscopic: Absorbs moisture; store in tightly closed, dry containers.

  2. Temperature Sensitivity: High temperature causes viscosity loss; store at -20°C.

  3. pH Sensitivity: pH below or above 7 causes viscosity loss.

  4. Enzyme Sensitivity: Hyaluronidase enzyme degrades HA.

  5. UV Sensitivity: UV rays degrade HA; protect from light.

  6. Microbial Contamination: Fermentation-derived products may contain endotoxins; endotoxin testing is mandatory for pharmaceutical grade.

  7. Molecular Weight: Different MWs have different applications; correct MW selection is critical.

BEST PRACTICE RECOMMENDATIONS:

  1. Form Selection: High MW (>1,000,000 Da) for joint injections; Medium MW (500,000-1,000,000 Da) for wound healing; Low MW (50,000-500,000 Da) for cosmetics; Very low MW (<50,000 Da) for transdermal applications.

  2. Dissolution: Dissolve slowly in water; avoid high-speed mixing (viscosity loss).

  3. pH Adjustment: Maintain pH 5.5-7.5.

  4. Temperature: Process at temperatures not exceeding 40°C.

  5. Preservatives: Add sodium benzoate, potassium sorbate, phenoxyethanol.

  6. Storage: Store at -20°C in a dry, dark place in tightly closed containers.

  7. Personal Protective Equipment: Dust mask, safety goggles, protective clothing.

LEGAL DISCLAIMER:

The information provided in this document is based on our current knowledge and experience and is presented in good faith. However, as all conditions of use are beyond our control, it does not constitute a binding specification or guarantee. This Technical Data Sheet is for informational purposes only. Users are responsible for testing suitability for their own applications and for complying with all local, regional, and national regulations. For complete safety, storage, use, handling, waste, and regulatory compliance information, please refer to the official Safety Data Sheet (SDS/MSDS) provided by the manufacturer/supplier.

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