技术文章

Multilevel Moisturizing Mechanisms of Sodium Hyaluronate and Its Derivatives: Molecular Weight Modulation, Crosslinking, Acetylation, and Major Sites of Action

Introduction

 

Sodium hyaluronate, crosslinked sodium hyaluronate polymers, sodium acetylated hyaluronate, and hydrolyzed sodium hyaluronate frequently appear together in moisturizing skincare products. They all retain the repeating disaccharide backbone of hyaluronic acid, but differ in molecular chain length, mode of linkage, or substituent groups. These structural differences give rise to distinct hydration capacities, viscoelasticity, film-forming properties, skin residence characteristics, and distributions within the stratum corneum.

 

The core principle of a combined hyaluronic acid system is to use structural differences to perform different water-management functions:

Crosslinked networks prolong water retention, high-molecular-weight linear chains form a surface hydration film, acetylated structures modulate interactions at the skin interface, and shorter chain segments improve hydration within the stratum corneum.

The synergistic action of these ingredients is based on the principle that “structure alters molecular behavior, and molecular behavior determines the site of action.”

 

1 Shared Structural Features and Hydration Basis of Sodium Hyaluronate

 

1.1 Relationship Between Hyaluronic Acid and Sodium Hyaluronate

Hyaluronic acid, abbreviated as HA, is a linear, non-sulfated glycosaminoglycan composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. The sugar units are linked by alternating β-1,3 and β-1,4 glycosidic bonds [1].

Sodium hyaluronate is the sodium salt form of hyaluronic acid. The two share the same polysaccharide backbone and differ mainly in the protonation or salt state of the carboxyl groups on the glucuronic acid residues and in the form of the counterion.

 

The carboxyl groups in hyaluronic acid can dissociate:

HA—COOH ⇌ HA—COO⁻ + H⁺

After sodium hyaluronate is formed, sodium ions serve as counterions for the carboxylate groups:

HA—COO⁻ · Na⁺

 

In aqueous environments close to neutral pH, the carboxyl groups of hyaluronic acid exist predominantly in the carboxylate form. Sodium hyaluronate has good water dispersibility and formulation compatibility and is therefore a commonly used form of hyaluronic acid in skincare products.

The relationships among sodium hyaluronate and its major structural derivatives are shown below.

 

Ingredient

Main Structural Characteristics

Core Structural Change

Sodium hyaluronate

Non-crosslinked linear polysaccharide sodium salt

Retains intact, long linear chains

Crosslinked sodium hyaluronate polymer

Multiple hyaluronic acid chains connected to one another

Conversion from linear chains into a three-dimensional network

Sodium acetylated hyaluronate

Acetyl groups introduced onto some hydroxyl groups

Alters the polarity distribution on the molecular surface

Hydrolyzed sodium hyaluronate

Long chains cleaved into shorter chain segments

Reduces the degree of polymerization and molecular weight

 

1.2 Why Sodium Hyaluronate Can Bind Water

The molecular chains of sodium hyaluronate contain numerous carboxylate, hydroxyl, and amide groups. These polar groups interact with water molecules through ion–dipole interactions and hydrogen bonding, forming hydration layers around the polymer chains.

This process can be represented in simplified form as:

HA—COO⁻ + nH₂O ⇌ HA—COO⁻·(H₂O)ₙ

Carboxylate groups carry negative charges, and electrostatic repulsion between neighboring charges gives hyaluronic acid chains a relatively large spatial dimension in water. As molecular weight increases, the chains gradually overlap and become entangled, increasing solution viscosity, viscoelasticity, and film-forming ability [2].

 

The moisturizing action of sodium hyaluronate mainly involves three consecutive processes:

1. Polar groups bind and organize surrounding water molecules;

2. Hydrated polymers slow the migration of water through the film layer;

3. Long-chain entanglement or crosslinked networks prolong the residence of water on the skin surface.

The role of sodium hyaluronate is to regulate the binding state, spatial distribution, and migration rate of water already present in the system.

 

2 How Molecular Weight Determines the Site of Action of Sodium Hyaluronate

 

2.1 Molecular Weight Alters Chain Size and Molecular Motion

The molecular weight of sodium hyaluronate depends on the number of repeating disaccharide units in the molecular chain. As molecular weight increases, the chain becomes longer, its hydrodynamic size increases, and chain overlap and entanglement become stronger. As molecular weight decreases, the chain segments become shorter, viscosity decreases, and diffusion becomes faster.

The principal performance differences associated with molecular weight are shown below.

 

Change in Molecular Weight

Properties Mainly Enhanced

Properties Relatively Reduced

Increased molecular weight

Viscosity, viscoelasticity, film formation, and surface residence

Diffusion within the stratum corneum

Decreased molecular weight

Fluidity, diffusion rate, and distribution within the stratum corneum

Interchain entanglement and film continuity

Further shortening of chain segments

Potential for interaction with keratinocytes

Ability to form a high-molecular-weight hydration film

 

2.2 High-Molecular-Weight Sodium Hyaluronate Forms a Surface Hydration Film

High-molecular-weight sodium hyaluronate forms large hydrated coils in water and produces a viscoelastic system through interchain entanglement. After application, as part of the water evaporates, the long chains form a continuous hydrophilic film on the surface of the stratum corneum.

 

Raman microscopic imaging showed that, under the conditions of the ex vivo skin study, hyaluronic acid with a molecular weight of 1,000–1,400 kDa remained mainly in the outer layers of the skin, whereas hyaluronic acid in the ranges of 20–50 kDa and 100–300 kDa showed more pronounced distribution within the stratum corneum [3]. These findings suggest that, compared with lower-molecular-weight samples, high-molecular-weight hyaluronic acid tends to remain on the skin surface and in the outer stratum corneum. Its advantage lies in hydration and film formation rather than penetration into the dermis to replenish the extracellular matrix.

 

2.3 Hydrolyzed Sodium Hyaluronate Enhances Diffusion Within the Stratum Corneum

Hydrolyzed sodium hyaluronate is produced by cleaving some glycosidic bonds through enzymatic hydrolysis, acid hydrolysis, or other controlled degradation processes, converting long chains into shorter chain segments. Hydrolysis is one method of obtaining shorter-chain hyaluronic acid, but “hydrolyzed sodium hyaluronate” and “low-molecular-weight hyaluronic acid” are not completely synonymous. The actual behavior of the ingredient still depends on its average molecular weight and molecular weight distribution.

The process can be represented in simplified form as:

Long-chain sodium hyaluronate

——enzymatic hydrolysis, acid-catalyzed hydrolysis, or other controlled degradation→ Shorter sodium hyaluronate chain segments

 

The following changes generally occur after hydrolysis:

① The average molecular weight decreases;

② The hydrodynamic size decreases;

③ Interchain entanglement is reduced;

④ Solution viscosity decreases;

⑤ Diffusion capacity increases;

⑥ The ability to form a continuous surface film decreases.

 

Under specific research and formulation conditions, shorter chain segments may show more pronounced distribution within the stratum corneum and may interact with water through carboxylate, hydroxyl, and amide groups. They therefore have the potential to improve water distribution within the stratum corneum.

The actual distribution of sodium hyaluronate in the skin is influenced not only by average molecular weight, but also by molecular weight distribution, ingredient concentration, formulation vehicle, application time, stratum corneum water content, and skin-barrier condition.

 

3 Crosslinked Sodium Hyaluronate Polymers: From Linear Long Chains to a Three-Dimensional Hydration Network

 

3.1 Crosslinking Alters the Mode of Molecular Connection

Linear sodium hyaluronate consists of long chains that are independent of or entangled with one another. Crosslinking creates connection points between different molecular chains, converting linear chains into a three-dimensional polymer network.

After crosslinking, the free movement of the hyaluronic acid chains is restricted. The network can absorb water and swell, but it does not diffuse rapidly through the aqueous phase in the same manner as linear molecules.

 

The actual properties of a crosslinked material depend on several structural parameters: the crosslinking agent and type of crosslinking bond; crosslink density; network particle size; equilibrium water uptake; swelling rate; and the proportion of soluble linear hyaluronic acid.

Therefore, even when different crosslinked sodium hyaluronate polymers share the same ingredient name, they may exhibit different water absorption, viscoelasticity, and skin residence properties.

 

3.2 How a Three-Dimensional Network Prolongs Water Residence

After water enters the crosslinked network, it fills the internal spaces and causes the polymer to swell. Crosslinking points prevent the chains from separating completely, allowing the hydrated structure to be maintained for a longer period.

The principal differences between crosslinked sodium hyaluronate and high-molecular-weight linear sodium hyaluronate are shown below.

 

Property

High-Molecular-Weight Sodium Hyaluronate

Crosslinked Sodium Hyaluronate Polymer

Molecular structure

Linear long chains with interchain entanglement

Covalently connected three-dimensional network

Mode of hydration

Forms hydrated coils and a continuous film layer

Absorbs water into the network and swells

Molecular migration

Can move to some extent with the aqueous phase

The network as a whole migrates more slowly

Main function

Surface film formation and immediate skin softness

Sustained water storage and prolonged residence

Main location

Skin surface and outer stratum corneum

Formulation film layer, skin surface, and outermost stratum corneum

 

In a human skin explant study, after daily treatment with a specific crosslinked resilient hyaluronic acid formulation, epidermal water content was 7.6% higher than that of the control on Day 9. On Day 2, transepidermal water loss was 27.8% lower than that of the control, while the high-molecular-weight linear hyaluronic acid group showed a 15.6% reduction [4].

These results reflect the effects of the specific crosslinked material on epidermal water distribution and barrier-related parameters. The main site of action of an intact crosslinked network remains in the outer layers of the skin, and its hydration effect does not require penetration into the viable epidermis or dermis.

 

4 Sodium Acetylated Hyaluronate: Modulation of Hydration Capacity and Skin-Interface Interactions

 

4.1 Acetylation Alters the Polarity Distribution on the Molecular Surface

Sodium acetylated hyaluronate is produced by introducing acetyl groups onto some of the hydroxyl groups of the sodium hyaluronate backbone.

The structural change can be represented in simplified form as:

HA—OH → HA—O—COCH₃

After acetylation, the carboxylate groups, amide groups, and unsubstituted hydroxyl groups of the hyaluronic acid backbone can still interact with water. The newly introduced acetyl groups alter the polarity distribution and spatial interactions of the molecular surface.

 

4.2 Molecular Weight and Degree of Acetylation Jointly Determine Performance

The effects of sodium acetylated hyaluronate are jointly determined by two principal parameters:

1. Molecular weight: affects chain size, diffusion capacity, and film-forming ability;

2. Degree of acetylation: affects polarity distribution, mode of hydration, and resistance to hyaluronidase degradation.

At a low degree of acetylation, the overall behavior of the molecule may remain similar to that of unmodified sodium hyaluronate. As the degree of acetylation increases, interactions between the molecule and the skin–water interface change accordingly. An excessively high degree of substitution may also affect the original water solubility and hydration characteristics.

 

One study compared fully acetylated sodium hyaluronate and non-acetylated sodium hyaluronate, both with a molecular weight of 15 kDa. Raman analysis showed that acetylation affected the distribution of the material in ex vivo skin. Hyaluronidase assays showed that the acetylated material had greater resistance to enzymatic degradation. Improvements in matrix metalloproteinase-related parameters and the appearance of wrinkles were also observed in cellular studies, skin explant studies, and human use tests [5].

 

These results were obtained using ingredients with specific molecular weights and degrees of acetylation and cannot be directly extrapolated to all sodium acetylated hyaluronate products. Current evidence supports that acetylation can alter the distribution of this material in ex vivo skin and improve its resistance to hyaluronidase degradation.

 

5 Low-Molecular-Weight Hyaluronic Acid and the Endogenous Moisturizing System of the Stratum Corneum

 

5.1 Direct Hydration and Natural Moisturizing Factor

After shorter hyaluronic acid chains enter the stratum corneum, they can bind water directly. This represents physical hydration produced by the polar groups of hyaluronic acid itself.

Corneocytes also contain natural moisturizing factor, or NMF, which mainly consists of free amino acids, pyrrolidone carboxylic acid, urocanic acid, and other hygroscopic small molecules. NMF is located within corneocytes and helps maintain the water content and flexibility of the stratum corneum.

 

One important source of NMF is the degradation of filaggrin.

The formation process can be summarized as:

Profilaggrin → Filaggrin → Proteolytic products → Free amino acids and their derivatives → NMF

 

5.2 Effects of Specific Low-Molecular-Weight Hyaluronic Acid on Filaggrin Metabolism and Natural Moisturizing Factor Formation

A three-dimensional reconstructed human epidermis study evaluated a specific low-molecular-weight hyaluronic acid of less than 10 kDa. The study showed that the material increased parameters related to profilaggrin, involucrin, caspase-14, and bleomycin hydrolase [6]. Caspase-14 and bleomycin hydrolase participate in the subsequent degradation of filaggrin, and filaggrin degradation products are an important source of NMF.

The study indicates that, in addition to directly binding water, the specific low-molecular-weight hyaluronic acid may also affect keratinocyte differentiation and processes related to filaggrin metabolism and natural moisturizing factor formation.

 

It should be noted that the biological effects of low-molecular-weight hyaluronic acid depend on molecular weight, concentration, and the experimental model. The results obtained with the specific material described above cannot be directly extrapolated to all low-molecular-weight or oligomeric hyaluronic acid products [7,8].

 

6 Major Distribution Patterns and Functional Tendencies of Different Hyaluronic Acid Ingredients

 

Sodium hyaluronate and its derivatives can perform different functions from the outermost layers inward according to their principal sites of action.

 

Main Site of Action

Main Ingredient

Molecular Behavior

Main Function

Formulation film layer and skin surface

Crosslinked sodium hyaluronate polymer

Three-dimensional network absorbs water and swells, with relatively slow overall migration

Establishes a sustained hydration layer and prolongs water residence

Skin surface and outer stratum corneum

High-molecular-weight sodium hyaluronate

Long chains hydrate, become entangled, and form a continuous film

Provides immediate hydration, softens the skin, and improves the appearance of dry lines

Skin surface–stratum corneum interface, with the specific distribution depending on molecular weight, degree of acetylation, and formulation conditions

Sodium acetylated hyaluronate

Changes in surface polarity distribution and resistance to enzymatic degradation

Maintains hydration and improves the resistance of specific materials to hyaluronidase degradation

Within the stratum corneum

Hydrolyzed sodium hyaluronate

Shorter chain segments diffuse and bind water

Improves water distribution within the stratum corneum

Lower stratum corneum or superficial viable epidermis

Specific low-molecular-weight hyaluronic acid

May interact with keratinocytes

May support epidermal differentiation and processes related to FLG and NMF

 

These sites of action are not completely separate and may overlap to some extent. The actual distribution of each ingredient is also affected by molecular weight, crosslinking status, degree of acetylation, use concentration, and formulation vehicle.

The multilevel, complementary moisturizing mechanisms of sodium hyaluronate and its derivatives are illustrated below. The figure primarily presents the distribution tendencies and functional roles of different ingredients. It does not indicate that the ingredients are sequentially converted into one another, nor does it imply absolute boundaries between their sites of action.

 

 

 

7 How Combined Hyaluronic Acid Systems Produce Multilevel, Complementary Moisturization

 

7.1 Crosslinked Networks Establish an Outer Water-Storage Region

After the product is applied, the crosslinked sodium hyaluronate polymer absorbs water from the formulation and swells. The three-dimensional network restricts the rapid migration of polymer chains and water, creating a hydrated region with a relatively long residence time on the skin surface.

This structure mainly addresses how water can be retained for a longer period in the outer layers of the skin.

 

7.2 High-Molecular-Weight Sodium Hyaluronate Forms a Continuous Hydration Film

High-molecular-weight sodium hyaluronate expands in the aqueous phase and undergoes interchain entanglement. As water gradually decreases, the linear long chains form a soft, continuous hydrophilic film on the surface of the stratum corneum.

The crosslinked network primarily contributes to water storage, whereas the high-molecular-weight linear chains primarily contribute to spreading and film formation. Together, these structures improve the uniformity and persistence of water coverage.

 

7.3 Sodium Acetylated Hyaluronate Enhances Interfacial Residence

By altering the polarity distribution of the molecular surface, sodium acetylated hyaluronate can affect its mode of hydration, resistance to enzymatic degradation, and distribution in skin models. Research on a specific 15 kDa material showed that acetylation altered its distribution in ex vivo skin and increased its resistance to hyaluronidase degradation. Actual performance still depends on molecular weight, degree of acetylation, and formulation conditions.

 

7.4 Hydrolyzed Sodium Hyaluronate Improves Hydration Within the Stratum Corneum

The shorter chain segments in hydrolyzed sodium hyaluronate have relatively high diffusion capacity. Under specific research and formulation conditions, they may show more pronounced distribution within the stratum corneum and interact with water in the corresponding regions.

Some low-molecular-weight hyaluronic acid materials with clearly defined molecular weights and supporting experimental data may also affect keratinocyte differentiation and processes related to FLG and NMF.

 

8 Combined Hyaluronic Acid Systems and Skin-Barrier Moisturization

 

Sodium hyaluronate and its derivatives mainly contribute to water binding, storage, residence, and distribution within the stratum corneum. The ability of the skin to retain water over the long term is also influenced by the structure of intercellular lipids in the stratum corneum.

Combined hyaluronic acid systems and barrier lipids perform different functions:

 

System

Main Function

Sodium hyaluronate and its derivatives

Bind water, form a hydration film, prolong residence, and improve water distribution within the stratum corneum

Small-molecule humectants such as glycerol and amino acids

Bind water within the stratum corneum and the aqueous phase of the formulation

Oils, esters, and fatty alcohols

Improve skin softness and surface lubrication

Ceramides, cholesterol, and free fatty acids

Support the structure of intercellular lipids in the stratum corneum

Occlusive film-forming ingredients

Slow the outward diffusion of water into the environment

 

Combined hyaluronic acid systems can improve skin hydration but cannot replace the lipids of the stratum corneum. A rational formulation should coordinate humectancy, hydration, emolliency, and reduction of water loss, while avoiding film contraction, tackiness, or tightness caused by high concentrations of hydrophilic polymers under low-humidity conditions.

 

9 Classification and Research Applications of Chemicals Related to Sodium Hyaluronate and Its Derivatives

 

Table 1 Core Hyaluronic Acid Ingredients, Salt Forms, and Molecular-Weight Series

 

Classification

CAS No.

Aladdin Cat. No.

Name

Specification or Purity

Product Features and Applications

Hyaluronic acid parent compound

9004-61-9

H131007

Hyaluronic Acid

Moligand™, from rooster comb

Used for studies of the repeating disaccharide backbone of hyaluronic acid, carboxyl-group dissociation, conversion between acid and salt forms, molecular-chain hydration, and viscoelastic properties.

Potassium hyaluronate salt control

31799-91-4

P303424

Potassium Hyaluronate (HA-K)

From rooster comb

Used to compare the solubility, hydration state, ionic-strength response, and rheological properties of hyaluronic acid with different counterions.

General-purpose sodium hyaluronate ingredient

9067-32-7

H107141

Sodium Hyaluronate, from Streptococcus equi

≥95%

Used for studies of sodium hyaluronate hydration, viscosity, chain conformation, surface film formation, and materials derived from microbial fermentation.

Medium-to-low-molecular-weight sodium hyaluronate

9067-32-7

H293507

Low-Molecular-Weight Sodium Hyaluronate (HA-TLM 20-40)

Molecular weight: 200–400 kDa

Used for studies of stratum corneum distribution, hydration capacity, diffusion behavior, and compatibility with high-molecular-weight ingredients.

High-molecular-weight sodium hyaluronate

9067-32-7

S1519976

Sodium Hyaluronate

Molecular weight: 600,000–1,200,000

Used for studies of long-chain hydration, interchain entanglement, solution viscoelasticity, film formation on the skin surface, and immediate moisturization.

Ultra-high-molecular-weight sodium hyaluronate

9067-32-7

S1519988

Sodium Hyaluronate

Molecular weight: 1,900,000–3,900,000

Used for studies of ultra-long-chain entanglement, viscosity development, surface hydration-film stability, and regulation of water migration.

Ultra-high-molecular-weight sodium hyaluronate

9067-32-7

H293496

High-Molecular-Weight Sodium Hyaluronate (HA-THM)

Molecular weight: ≥1.8 MDa

Used for studies of high-molecular-weight sodium hyaluronate film formation, surface residence, viscoelastic networks, and hydration of the outer stratum corneum.

Medium-to-low-molecular-weight sodium hyaluronate

9067-32-7

H758878

Sodium Hyaluronate

≥95%, molecular weight: 50,000–70,000

Used for studies of molecular-weight gradients, stratum corneum diffusion, internal hydration, and synergistic formulation with long-chain sodium hyaluronate.

Low-molecular-weight sodium hyaluronate

9067-32-7

H758875

Sodium Hyaluronate

≥95%, molecular weight: 30,000–50,000

Used for studies of the diffusion rate, stratum corneum distribution, hydration state, and chain-length effects of low-molecular-weight sodium hyaluronate.

Low-molecular-weight sodium hyaluronate

9067-32-7

H758871

Sodium Hyaluronate

≥95%, molecular weight: 15,000–30,000

Used for studies of the distribution of shorter hyaluronic acid chains within the stratum corneum, direct hydration, and molecular-weight-dependent effects.

Ultra-low-molecular-weight sodium hyaluronate

9067-32-7

H758869

Sodium Hyaluronate

≥95% (HPLC), molecular weight: 7,000–12,000

Used for studies of stratum corneum diffusion, epidermal-model responses, and filaggrin-related mechanisms involving ultra-low-molecular-weight sodium hyaluronate.

Enzymatically cleaved oligomeric sodium hyaluronate

9067-32-7

E293520

Enzymatically Cleaved Oligomeric Sodium Hyaluronate

Molecular weight: <10 kDa

Used for studies of the molecular-weight distribution, diffusion within the stratum corneum, cellular responses, and natural moisturizing factor-related processes of enzymatically cleaved oligomeric chains.

Ultra-low-molecular-weight sodium hyaluronate

9067-32-7

U293516

Ultra-Active Hyaluronic Acid

Molecular weight: <5 kDa

Used for studies of the diffusion behavior of hyaluronic acid oligomers, keratinocyte responses, epidermal differentiation, and filaggrin metabolism.

 

Table 2 Reagents for Studies of Hyaluronic Acid Structural Composition, Crosslinking Modification, Acetylation, and Degradation

 

Classification

CAS No.

Aladdin Cat. No.

Name

Specification or Purity

Product Features and Applications

Uronic acid control for the repeating unit

6556-12-3

G105701

D-Glucuronic Acid

Moligand™, ≥98%

Used for studies of the repeating disaccharide composition, carboxyl structure, monosaccharide composition analysis, and identification of hydrolysis products of hyaluronic acid.

Amino sugar control for the repeating unit

7512-17-6

A105211

N-Acetyl-D-Glucosamine

≥98%

Used for analysis of the repeating disaccharide composition, acetamido structure, hydrolysis products, and monosaccharide quantification of hyaluronic acid.

Amino sugar structural control

66-84-2

G100089

D-(+)-Glucosamine Hydrochloride

≥99%

Used as a deacetylated structural control for N-acetyl-D-glucosamine and for studies of amino sugar analysis and degradation products.

Uronic acid lactone control

32449-92-6

G100817

D-Glucuronic Acid Lactone

≥99%

Used for studies of glucuronic acid lactonization, structural transformation under acidic conditions, and analysis of hyaluronic acid degradation products.

Hyaluronidase digestion reagent

9001-54-1

H304866

Hyaluronidase from Bovine Testes

EnzymoPure™, ≥400 U/mg

Used for enzymatic degradation of hyaluronic acid, molecular-weight reduction, degradation-kinetics studies, and evaluation of the resistance of crosslinked or acetylated materials to enzymatic degradation.

Epoxy-type crosslinking agent

2425-79-8

B109380

1,4-Butanediol Diglycidyl Ether (BDDE)

≥95%

Used for hydroxyl-group crosslinking of hyaluronic acid, hydrogel-network construction, and studies of crosslink density, water absorption, swelling, and viscoelastic properties.

Hydrazide-type crosslinking agent

1071-93-8

A109760

Adipic Acid Dihydrazide (ADH)

≥99% (HPLC)

Used for hydrazide functionalization of hyaluronic acid carboxyl groups, carbodiimide-mediated crosslinking, hydrogel construction, and network-stability studies.

Carboxyl-activating coupling reagent

25952-53-8

E106172

1-Ethyl-3-(3-Dimethylaminopropyl)carbodiimide Hydrochloride

≥98%

Used for activation of hyaluronic acid carboxyl groups, amide-bond formation, hydrazide crosslinking, and functional-group grafting studies.

Carboxyl-activation additive

6066-82-6

H109330

N-Hydroxysuccinimide (NHS)

≥98%

Used to stabilize activated intermediates of hyaluronic acid carboxyl groups, improve amidation efficiency, and investigate crosslinking conditions.

Acetylation reagent

108-24-7

A1506320

Acetic Anhydride (Regulated Precursor Chemical)

European Pharmacopoeia (Ph. Eur.), puriss. p.a., ISO, ACS, ≥99% (GC)

Used for hydroxyl-group acetylation of hyaluronic acid, regulation of the degree of acetyl substitution, and preparation of acetylated hyaluronic acid structures.

Acetylation reaction medium

64-19-7

A116166

Glacial Acetic Acid

Guaranteed reagent, ≥99.5%

Used as a reaction medium for hyaluronic acid acetylation, for adjustment of acidic conditions, and for control of the degree of acetylation.

Alkaline reaction and neutralization reagent

1310-73-2

S111498

Sodium Hydroxide

Guaranteed reagent, ≥96%

Used for formation of the sodium salt of hyaluronic acid, ionization of carboxyl groups, establishment of alkaline crosslinking conditions, and post-reaction neutralization.

Ionic-strength adjustment reagent

7647-14-5

S433744

Sodium Chloride

Anhydrous grade, reagent grade, high purity, ≥99%

Used for studies of hyaluronic acid polyelectrolyte-chain conformation, ionic screening, hydration layers, solution viscosity, and osmotic pressure.

Acid-hydrolysis and acidity-adjustment reagent

7647-01-0

H475775

Hydrogen Chloride (Regulated Precursor Chemical)

Reagent grade, high purity, ≥99%

Used for acid hydrolysis of hyaluronic acid, molecular-weight regulation, glycosidic-bond stability studies, and adjustment of reaction-system acidity.

 

Table 3 Control Products for Studies of Natural Moisturizing Factor, Stratum Corneum Hydration, and Barrier Lipids

 

Classification

CAS No.

Aladdin Cat. No.

Name

Specification or Purity

Product Features and Applications

Core natural moisturizing factor component

28874-51-3

L303332

Sodium L-Pyrrolidone-5-Carboxylate

50% oily liquid

Used for studies of natural moisturizing factor composition, hygroscopicity within corneocytes, synergy between hyaluronic acid and small-molecule moisturizers, and comparison of hydration capacity.

Acid-form natural moisturizing factor control

98-79-3

L434627

L-Pyroglutamic Acid

UltraBio™, ultrapure grade

Used for studies of the acid-form structure of pyrrolidone carboxylic acid, acid–base balance of natural moisturizing factor, and moisturizing mechanisms in the stratum corneum.

Filaggrin-degradation amino acid control

56-45-1

S137887

L-Serine

Animal-origin-free, USP, Moligand™, European Pharmacopoeia (Ph. Eur.), ≥98.5%

Used for studies of filaggrin degradation products, the amino acid composition of natural moisturizing factor, and stratum corneum hydration.

Filaggrin-degradation amino acid control

56-41-7

L432936

L-Alanine

UltraBio™, ultrapure grade, ≥99.5% (NT)

Used for studies of free amino acid composition in the stratum corneum, natural moisturizing factor quantification, and mechanisms of action of low-molecular-weight hyaluronic acid.

Filaggrin-degradation amino acid control

71-00-1

L755708

L-Histidine

UltraBio™, ≥99.5% (NT)

Used for studies of filaggrin degradation, histidine metabolism, urocanic acid formation, and natural moisturizing factor in the stratum corneum.

Filaggrin-degradation amino acid control

74-79-3

A137768

L-Arginine

Moligand™, ≥99% (HPLC)

Used for studies of free amino acid composition in the stratum corneum, acid–base buffering, natural moisturizing factor, and hydration state.

Histidine metabolite control

104-98-3

I165655

4-Imidazoleacrylic Acid

≥98%

Used for studies of urocanic acid structure, histidine metabolism, natural moisturizing factor composition, and the acidic environment of the stratum corneum.

Small-molecule humectant control

56-81-5

G755728

Glycerol

Anhydrous grade, UltraBio™, molecular biology grade, ≥99.5% (GC)

Used for studies of small-molecule humectancy, stratum corneum hydration, persistence of moisturization, and compatibility with sodium hyaluronate of different molecular weights.

Natural moisturizing factor and keratin-hydration control

57-13-6

U432960

Urea

Crystalline, pharmaceutical grade, Ph. Eur., BP, ChP, JP, USP

Used for studies of natural moisturizing factor composition, keratin hydration, stratum corneum softness, and combined hyaluronic acid moisturizing systems.

Stratum corneum barrier-lipid control

57-88-5

C432975

Cholesterol, from Lanolin

PharmPure™, JP, BP, European Pharmacopoeia (Ph. Eur.), NF, ultrapure grade

Used for studies of intercellular lipid models of the stratum corneum, barrier structure, transepidermal water loss, and compatibility with hyaluronic acid hydration systems.

Essential fatty acid and barrier-lipid control

60-33-3

L100441

Linoleic Acid

Moligand™, ≥99% (GC)

Used for studies of free fatty acid composition, stratum corneum lipid organization, barrier function, and synergistic mechanisms between hydration and lipids.

 

Note: The crosslinking, coupling, acetylation, and hydrolysis reagents listed above are primarily intended for laboratory preparation and mechanistic research and are not equivalent to finished ingredients that can be directly incorporated into cosmetic formulations. Additional product specifications, grades, and certificate of analysis information can be retrieved from the Aladdin website by searching the product name, CAS number, or catalog number.

 

References

 

[1] Simpson M, Schaefer L, Hascall V, Esko JD. Hyaluronan. In: Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology. 4th ed. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2022.

 

[2] Cowman MK, Schmidt TA, Raghavan P, Stecco A. Viscoelastic properties of hyaluronan in physiological conditions. F1000Research. 2015;4:622.

 

[3] Essendoubi M, Gobinet C, Reynaud R, Angiboust JF, Manfait M, Piot O. Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. Skin Research and Technology. 2016;22(1):55–62.

 

[4] Sundaram H, Mackiewicz N, Burton E, Peno-Mazzarino L, Lati E, Meunier S. Pilot comparative study of the topical action of a novel, crosslinked resilient hyaluronic acid on skin hydration and barrier function in a dynamic, three-dimensional human explant model. Journal of Drugs in Dermatology. 2016;15(4):434–441.

 

[5] Meunier M, Scandolera A, Chapuis E, et al. The anti-wrinkles properties of sodium acetylated hyaluronate. Journal of Cosmetic Dermatology. 2022;21(7):2749–2762.

 

[6] Hashimoto M, Maeda K. New functions of low-molecular-weight hyaluronic acid on epidermis filaggrin production and degradation. Cosmetics. 2021;8(4):118.

 

[7] Cyphert JM, Trempus CS, Garantziotis S. Size matters: molecular weight specificity of hyaluronan effects in cell biology. International Journal of Cell Biology. 2015;2015:563818.

 

[8] Tavianatou AG, Caon I, Franchi M, Piperigkou Z, Galesso D, Karamanos NK. Hyaluronan: molecular size-dependent signaling and biological functions in inflammation and cancer. The FEBS Journal. 2019;286(15):2883–2908.

 

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目录: 技术文章

Da — 若无特别说明,分子量单位默认为道尔顿。   Mw — 重均分子量。   Mn — 数均分子量。

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引用本文

阿拉丁科学.《Multilevel Moisturizing Mechanisms of Sodium Hyaluronate and Its Derivatives: Molecular Weight Modulation, Crosslinking, Acetylation, and Major Sites of Action》. 阿拉丁知识库,更新于 2026年8月24日。 https://www.aladdin-e.com/zh_cn/faqs/multilevel-moisturizing-mechanisms-of-sodium-hyaluronate-and-its-derivatives-en.html
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