HYALURONATE

Hyaluronate (abbreviated HA; conjugate base Hyaluronan), also called Hyaluronic acid, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues.
Hyaluronate is naturally found in many areas of the human body, including the skin, eyes, and synovial fluid of the joints.
Hyaluronate (pronounced hi-ah-lew-ron-ic) acid also known as Hyaluronic acid or Hyaluronan is a gooey, slippery substance that your body produces naturally.

CAS Number: 9004-61-9
EC Number: 232-678-0
Chemical Formula: (C14H21NO11)n
Molecular Weight: 425.38 g/mol

HYALURONIC ACID SODIUM, acid hyaluronic, Hyaluronic acid powder, aluronic acid HA, Hyaluronate Acid, HYALURONIC ACID (SODIUM HYALURONATE), Hyaluronic acid, bovine vitreous humor, Mucoitin, Sepracoat, hyaluronicaci, Hyaluronic Acid, MW 3,000, Hyaluronic Acid, MW 10,000, Hyaluronic Acid, MW 25,000, Hyaluronic Acid, MW 50,000, Hyaluronic Acid, MW 100,000, Hyaluronic Acid, MW 350,000, Hyaluronic Acid, MW 1,000,000, Hyaluronic Acid, MW 1,500,000, BP-29024, BP-29025, BP-29026, BP-29027, BP-29028, BP-29029, BP-29030, BP-29031, Hyaluronic acid, 57282-61-8 [RN], Hyaluronate Tetrasaccharide, NAG-(3-1)GCU-(4-1)NAG-(3-1)GCU

Hyaluronate is a humectant a substance that retains moisture and Hyaluronate is capable of binding over one thousand times Hyaluronate weight in water.
Hyaluronate is naturally found in many areas of the human body, including the skin, eyes, and synovial fluid of the joints.
Hyaluronate used in beauty and skincare products is primarily made by bacteria in a lab via a process called biofermentation.

As we age, the production of key substances in the skin, including Hyaluronate (along with collagen and elastin) decreases.
As a result, our skin loses volume, hydration, and plumpness.

Hyaluronate is a natural substance found in the fluids in the eyes and joints.
Hyaluronate acts as a cushion and lubricant in the joints and other tissues.

Different forms of Hyaluronate are used for cosmetic purposes.
Hyaluronate might also affect the way the body responds to injury and help to decrease swelling.

People also commonly take Hyaluronate by mouth and apply Hyaluronate to the skin for UTIs, acid reflux, dry eyes, wound healing, aging skin, and many other conditions, but there is no good scientific evidence to support most of these other uses.

Hyaluronate is a gooey, slippery substance that your body produces naturally.
Scientists have found Hyaluronate throughout the body, especially in eyes, joints and skin.

Hyaluronate is often produced by fermenting certain types of bacteria.
Rooster combs (the red, Mohawk-like growth on top of a rooster’s head and face) are also a common source.

Hyaluronate (pronounced hi-ah-lew-ron-ic) acid also known as Hyaluronic acid or Hyaluronan is a gooey, slippery substance that your body produces naturally.
Scientists have found Hyaluronate throughout the body, especially in eyes, joints and skin.

Hyaluronate (abbreviated HA; conjugate base Hyaluronan), also called Hyaluronic acid, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues.
Hyaluronate is unique among glycosaminoglycans as Hyaluronate is non-sulfated, forms in the plasma membrane instead of the Golgi apparatus, and can be very large: human synovial Hyaluronate averages about 7 million Da per molecule, or about 20,000 disaccharide monomers, while other sources mention 3–4 million Da.

The average 70 kg (150 lb) person has roughly 15 grams of Hyaluronate in the body, one third of which is turned over (i.e., degraded and synthesized) per day.

As one of the chief components of the extracellular matrix, Hyaluronate contributes significantly to cell proliferation and migration, and is involved in the progression of many malignant tumors.
Hyaluronate is also a component of the group A streptococcal extracellular capsule, and is believed to play a role in virulence.

Hyaluronate, derived from the name hyalos meaning glass, is found in the human body.
Hyaluronate is known for its structural ability to hold approximately a thousand times as much water as itself.

Thanks to this feature, Hyaluronate has an important place in the healthy movement of muscles and bones.
At the same time, the decrease in Hyaluronate in the structure of the skin, which is the largest organ of our body, can cause skin dryness and wrinkles.
Hyaluronate application for the skin is among Hyaluronates frequently used as anti-aging.

Hyaluronate occurs naturally in the body but can be produced from animal sources or bacteria.
Hyaluronate can be found in various forms such as powder, tablet and liquid for oral intake.

In addition, there are also cream, ointment and serum types to be applied to the skin.
Additionally, Hyaluronate can be recommended as eye drops to relieve eye dryness during eye surgery or contact lens use.

Hyaluronate may sound intimidating many of us wouldn't dream of putting acid on our faces but science shows us Hyaluronate brilliant in skincare.
Hyaluronate is a gel-like substance that has the unique ability to retain moisture.

In fact, our bodies produce Hyaluronate naturally to keep our skin soft and supple.
Hyaluronate also found in our eyes, joints, and connective tissue.
So Hyaluronate works wonderfully as an anti-aging component in face creams and serums, as the Hyaluronate can hold over 1,000 times Hyaluronate weight in water. 

Hyaluronate is a completely transparent, non-adhesive, water-soluble and grease-free acid mucopolysaccharide.
Hyaluronate molecular weight is between a few hundred thousand to millions, and Hyaluronate makes up the dermis layer of the skin.

Hyaluronate unique molecular structure and physicochemical properties has many important physiological functions inside the body, such as lubricating joints, adjusting vascular permeability, adjusting proteins, diffusing and transporting water electrolytes, and promoting wound healing.
Hyaluronate has a unique water retention effect and has the best known natural moisturizing properties, making Hyaluronate the ideal natural moisturizer.

Hyaluronate is an essential drug in ophthalmic “sticky surgeries”.
Hyaluronate is used in cataract surgery, in which Hyaluronate sodium salt remains in the anterior chamber to maintain depth in the anterior chamber and ensure a clear surgical view.

Hyaluronate reduces the occurences of postoperative inflammation and complications, thus improving the vision-correcting effects of the surgery.
Hyaluronate is also used in complicated retinol detachment surgery.

Hyaluronate has a low molecular weight and is considered the ideal natural moisturizing agent, so Hyaluronate is used as an additive in high-end makeup and as a moisturizer in creams, gels, lotions, masks, and serums.
Hyaluronate is also used medically as a moisturizer to improve moisture retention and lubrication, and Hyaluronate also expands capillaries and improves skin health.
For example, Hyaluronate with a low molecular weight can be used as a lubricant in surgeries (such as knee surgery), while those with high molecular weight can be used as surgical lubricant and as a substitute for vitreous in ophthalmic surgery.

Hyaluronate is a naturally occurring glycosaminoglycan found throughout the body’s connective tissue.
Glycosaminoglycans are simply long unbranched carbohydrates, or sugars, called polysaccharides.

Hyaluronate is the main component of what gives your skin structure, and is responsible for that plump and hydrated look.
Hyaluronate plays a pivotal role in the wound healing process, and decreases as we age making us more susceptible to sagging and wrinkles.

Hyaluronate can help increase the moisture content in your skin, which can have various skin benefits, including reducing the appearance of wrinkles and improving wound healing, among others.

Skin aging is a multifactorial process consisting of two distinct and independent mechanisms: intrinsic and extrinsic aging.

Youthful skin retains Hyaluronate turgor, resilience and pliability, among others, due to Hyaluronate high content of water.
Daily external injury, in addition to the normal process of aging, causes loss of moisture.

The key molecule involved in skin moisture is Hyaluronate that has unique capacity in retaining water.
There are multiple sites for the control of Hyaluronate synthesis, deposition, cell and protein association and degradation, reflecting the complexity of Hyaluronate metabolism.

The enzymes that synthesize or catabolize Hyaluronate and Hyaluronate receptors responsible for many of the functions of Hyaluronate are all multigene families with distinct patterns of tissue expression.
Understanding the metabolism of Hyaluronate in the different layers of the skin and the interactions of Hyaluronate with other skin components will facilitate the ability to modulate skin moisture in a rational manner.

There are 2 types of Hyaluronate:

Micro Molecular Hyaluronate:
In this type of Hyaluronate, the molecules consist of low-weight micro molecules.
With their micro size, they can penetrate down to the epidermis layer of the skin, penetrate under the skin and repair any damage there.

Micromolecular Hyaluronate can act under the tissue and moisturize the skin from within.
This type of molecule can promote the natural production of Hyaluronate under the skin.

Macro Molecular Hyaluronate:
This Hyaluronate can be described as high molecular weight.
Hyaluronate usually does not go under the skin.

Due to this feature, Hyaluronate can make repairs on the skin surface.
Additionally, Hyaluronate is effective in moisturizing the skin surface and gaining elasticity.

Uses of Hyaluronate:
Hyaluronate is a naturally derived, non immunogenic, non adhesive glycosaminoglycan that plays a prominent role in various wound healing processes, as Hyaluronate as Hyaluronate is naturally angiogenic when degraded to small fragments.
Hyaluronate promotes early inflammation which is critical for initiating wound healing, but then moderates later stages of the process, allowing matrix stabilization and reduction of long term inflammation.
Hyaluronate is a main source for pharmaceutical, medical and cosmetic application.

Hyaluronate is a glycosaminoglycan component.
Hyaluronate occurs naturally in the dermis.

Hyaluronate is thought to play a critical role in healthy skin by controlling the physical and biochemical characteristics of epidermal cells.
Hyaluronate also regulates general skin activity, such as water content, elasticity, and the distribution of nutrients.

Hyaluronate water-absorption abilities and large molecular structure allow the epidermis to achieve greater suppleness, proper plasticity, and turgor.
Hyaluronate is a natural moisturizer with excellent water-binding capabilities.

In a solution of 2 percent Hyaluronate and 98 percent water, the Hyaluronate holds the water so tightly that Hyaluronate appears to create a gel.
However, Hyaluronate is a true liquid in that Hyaluronate can be diluted and will exhibit a liquid’s normal viscous flow properties.

When applied to the skin, Hyaluronate forms a viscoelastic film in a manner similar to the way Hyaluronate holds water in the intercellular matrix of dermal connective tissues.
This performance and behavior suggests that Hyaluronate makes an ideal moisturizer base, allowing for the delivery of other agents to the skin.

Manufacturers claim that the use of Hyaluronate in cosmetics results in the need for much lower levels of lubricants and emollients in a formulation, thereby providing an essentially greaseless product.
Furthermore, Hyaluronate ability to retain water gives immediate smoothness to rough skin surfaces and significantly improves skin appearance.
For the benefits of Hyaluronate to be realized in a cosmetic, Hyaluronate needs to be applied on a regular basis as Hyaluronate is broken down in skin within 24 to 48 hours of application.

Some people use Hyaluronate to promote skin health and fight signs of aging.
Hyaluronate may help wounds heal, too.

Some doctors also use Hyaluronate to relieve joint pain in people with arthritis.

The skin contains about half of the Hyaluronate in the body. 
Hyaluronate binds to water molecules, which helps keep the skin hydrated and supple.

Levels of Hyaluronate in the skin significantly decrease as people age, which can lead to dehydrated skin and wrinkles.
Taking Hyaluronate or using cosmetic products that contain Hyaluronate may improve skin hydration and reduce signs of aging.

Use for Animal Health of Hyaluronate:
Hyaluronate is used in treatment of articular disorders in horses, in particular those in competition or heavy work.
Hyaluronate is indicated for carpal and fetlock joint dysfunctions, but not when joint sepsis or fracture are suspected.

Hyaluronate is especially used for synovitis associated with equine osteoarthritis.
Hyaluronate can be injected directly into an affected joint, or intravenously for less localized disorders.

Hyaluronate may cause mild heating of the joint if directly injected, but this does not affect the clinical outcome.
Intra-articularly administered medicine is fully metabolized in less than a week.

According to Canadian regulation, Hyaluronate in HY-50 preparation should not be administered to animals to be slaughtered for horse meat.
In Europe, however, the same preparation is not considered to have any such effect, and edibility of the horse meat is not affected.

Medical uses:
Hyaluronate has been FDA-approved to treat osteoarthritis of the knee via intra-articular injection.
A 2012 review showed that the quality of studies supporting this use was mostly poor, with a general absence of significant benefits, and that intra-articular injection of Hyaluronate could possibly cause adverse effects.
A 2020 meta-analysis found that intra-articular injection of high molecular weight Hyaluronate improved both pain and function in people with knee osteoarthritis.

Hyaluronate has been used to treat dry eye.
Hyaluronate is a common ingredient in skin care products.

Hyaluronate is used as a dermal filler in cosmetic surgery.
Hyaluronate is typically injected using either a classic sharp hypodermic needle or a micro-cannula.

Some studies have suggested that the use of micro-cannulas can significantly reduce vessel embolisms during injections.
Currently, Hyaluronate is used as a soft tissue filler due to Hyaluronate bio-compatibility and possible reversibility using hyaluronidase.

Complications include the severing of nerves and microvessels, pain, and bruising.
Some side effects can also appear by way of erythema, itching, and vascular occlusion; vascular occlusion is the most worrisome side effect due to the possibility of skin necrosis, or even blindness in a patient.
In some cases, Hyaluronate fillers can result in a granulomatous foreign body reaction.

Uses Area of Hyaluronate:
Hyaluronate is a remarkable substance because of all the benefits and uses Hyaluronate has in your body.

Here are just a few of the benefits of Hyaluronate:
Hyaluronate helps things move smoothly.
Hyaluronate helps your joints work like a well-oiled machine.

Hyaluronate prevents pain and injury from bones grinding against each other.
Hyaluronate helps keep things hydrated.

Hyaluronate is very good at retaining water.
A quarter-teaspoon of Hyaluronate holds about one and a half gallons of water.

That’s why Hyaluronate is often used for treating dry eyes.
It’s also used in moisturizing creams, lotions, ointments and serums.

Hyaluronate makes your skin flexible.
Hyaluronate helps skin stretch and flex and reduces skin wrinkles and lines.
Hyaluronate is also proven to help wounds heal faster and can reduce scarring.

Sources of Hyaluronate:
Hyaluronate is produced on a large scale by extraction from animal tissues, such as chicken comb, and from Streptococci.

Benefits of Hyaluronate:

Promotes healthier, more supple skin:
Hyaluronate supplements can help your skin look and feel more supple.
Hyaluronate is a compound found naturally in the skin, where Hyaluronate binds to water to help retain moisture.

However, the natural aging process and exposure to things like ultraviolet radiation from the sun, tobacco smoke, and pollution can decrease Hyaluronate amounts in the skin.
Taking Hyaluronate supplements may prevent this decline by giving your body extra amounts to incorporate into the skin.

According to one 2014 study, doses of 120–240 milligrams (mg) per day for at least 1 month have been shown to significantly increase skin moisture and reduce dry skin in adults.
Hydrated skin also reduces the appearance of wrinkles, which may explain why several studies show that supplementing with Hyaluronate can make skin appear smoother.

When applied to the surface of the skin, Hyaluronate serums can reduce wrinkles, redness, and dermatitis.
Some dermatologists even inject Hyaluronate fillers to keep skin looking firm and youthful.

Can speed wound healing:
Hyaluronate also plays a key role in wound healing.
It’s naturally present in the skin, but Hyaluronate concentrations increase when there is damage in need of repair.

Hyaluronate helps wounds heal faster by regulating inflammation levels and signaling the body to build more blood vessels in the damaged area.
In some older studies, applying Hyaluronate to skin wounds has been shown to reduce the size of wounds and decrease pain faster than a placebo or no treatment at all.

Hyaluronate also has antibacterial properties, so Hyaluronate may help reduce the risk of infection when applied directly to open wounds.
What’s more, it’s effective at reducing gum disease, speeding up healing after tooth surgery, and eliminating ulcers when used topically in the mouth.

While the research on Hyaluronate serums and gels is promising, there has been no research to determine whether Hyaluronate supplements can provide the same benefits.
However, since oral supplements boost the levels of Hyaluronate found in the skin, it’s reasonable to suspect they may provide some benefit.

Relieve joint pain by keeping bones lubricated:
Hyaluronate is also found in the joints, where Hyaluronate keeps the space between your bones lubricated.
When the joints are lubricated, the bones are less likely to grind against each other and cause uncomfortable pain.

Hyaluronate supplements are very helpful for people with osteoarthritis, a type of degenerative joint disease caused by wear and tear on the joints over time.
Taking 80–200 mg daily for at least 2 months has been shown to significantly reduce knee pain in people with osteoarthritis, especially those between the ages of 40 and 70 years old.

Hyaluronate can also be injected directly into the joints for pain relief.
However, an analysis of over 21,000 adults found only a small reduction in pain and a greater risk of adverse effects.

Some research shows that pairing oral Hyaluronate supplements with injections can help extend pain-relieving benefits and increase the amount of time between shots.

Soothe acid reflux symptoms:
New research shows Hyaluronate supplements may help reduce symptoms of acid reflux.
When acid reflux occurs, the contents of the stomach are regurgitated up into the throat, causing pain and damage to the lining of the esophagus.

Hyaluronate may help soothe the damaged lining of the esophagus and speed up the recovery process.
One 2012 test-tube study found that applying a mixture of Hyaluronate and chondroitin sulfate to acid-damaged throat tissue helped Hyaluronate heal much faster than when no treatment was used.

Human studies have also shown benefits.
One study found that taking a Hyaluronate and chondroitin sulfate supplement along with an acid-reducing medication decreased reflux symptoms 60% more than taking acid-reducing medication alone.

Another older study showed that the same type of supplement was five times more effective at reducing acid reflux symptoms than a placebo.

Research in this area is still relatively new, and more studies are needed to replicate these results.
Nevertheless, these outcomes are promising.

Relieve dry eye and discomfort:
Approximately 11% older adults experience symptoms of dry eye due to reduced tear production or tears evaporating too quickly.
Since Hyaluronate is excellent at retaining moisture, it’s often used to treat dry eye.

Eye drops containing 0.2–0.4% Hyaluronate have been shown to reduce dry eye symptoms and improve eye health.
Contact lenses that contain slow-release Hyaluronate are also being developed as a possible treatment for dry eye.

In addition, Hyaluronate eye drops are frequently used during eye surgery to reduce inflammation and speed wound healing.
While applying them directly to the eyes has been shown to reduce dry eye symptoms and improve overall eye health, Hyaluronate is unclear whether oral supplements have the same effects.

One small study in 24 people found that combining topical and oral Hyaluronate was more effective at improving symptoms of dry eye than topical Hyaluronate alone.
However, more large, high-quality studies are needed to understand the effects of oral Hyaluronate supplements on eye health.

Preserve bone strength:
New animal research has begun to investigate the effects of Hyaluronate supplements on bone health.
Two older studies have found that Hyaluronate supplements can help slow the rate of bone loss in rats with osteopenia, the beginning stage of bone loss that precedes osteoporosis.

Some older test-tube studies have also shown that high doses of Hyaluronate can increase the activity of osteoblasts, the cells responsible for building new bone tissue.
While more high quality, recent research in humans is needed, early animal and test-tube studies are promising.

Could prevent bladder pain:
Approximately 3–6% of females suffer from a condition called interstitial cystitis, or painful bladder syndrome.
This disorder causes abdominal pain and tenderness, along with a strong and frequent urge to urinate.

While the causes of interstitial cystitis are unknown, Hyaluronate has been found to help relieve the pain and urinary frequency associated with this condition when inserted directly into the bladder through a catheter.
It’s unclear why Hyaluronate helps relieve these symptoms, but researchers hypothesize that Hyaluronate helps repair damage to bladder tissue, making Hyaluronate less sensitive to pain.

Studies have not yet determined whether oral Hyaluronate supplements can increase amounts of Hyaluronate in the bladder enough to have the same effects.

The benefits of Hyaluronate can be listed as follows:

Skin:
When Hyaluronate comes to Hyaluronate, the first thing that comes to mind is the skin.
Humidity decreases over time in the human body.

Lack of moisture can also cause wrinkles and other signs of aging, especially on the skin.
At this point, Hyaluronate has an important place in terms of giving the skin a vibrant appearance due to Hyaluronate water retention feature and ensuring the healing of wounds and skin blemishes.

Muscle and Joint:
Muscles and joints need intra-articular fluid to maintain their structural health.
Hyaluronate retains water and helps muscles and joints move smoothly and protects cartilage.

Eyelash:
Eye fluid naturally contains Hyaluronate.
Hyaluronate supports the natural health of the eye.

Hyaluronate is effective in protection.
At the same time, drops containing Hyaluronate may be recommended to treat dry eyes caused by lens use and some eye operations.

Although Hyaluronate has many benefits, a specialist should be consulted, especially in case of disease or damage.
A specialist doctor can recommend the form and treatment of Hyaluronate that is most suitable for the person.

Other Benefits:
anti-aging
moisturizing
wound healing
anti-wrinkle
increases skin elasticity
can treat eczema
can treat facial redness

Physiological Function of Hyaluronate:
Until the late 1970s, Hyaluronate was described as a "goo" molecule, a ubiquitous carbohydrate polymer that is part of the extracellular matrix.
For example, Hyaluronate is a major component of the synovial fluid and was found to increase the viscosity of the fluid.
Along with lubricin, Hyaluronate is one of the fluid's main lubricating components.

Hyaluronate is an important component of articular cartilage, where Hyaluronate is present as a coat around each cell (chondrocyte).
When aggrecan monomers bind to Hyaluronate in the presence of HAPLN1 (Hyaluronate and proteoglycan link protein 1), large, highly negatively charged aggregates form.

These aggregates imbibe water and are responsible for the resilience of cartilage (Hyaluronate resistance to compression).
The molecular weight (size) of Hyaluronate in cartilage decreases with age, but the amount increases.

A lubricating role of Hyaluronate in muscular connective tissues to enhance the sliding between adjacent tissue layers has been suggested.
A particular type of fibroblasts, embedded in dense fascial tissues, has been proposed as being cells specialized for the biosynthesis of the Hyaluronate-rich matrix.
Their related activity could be involved in regulating the sliding ability between adjacent muscular connective tissues.

Hyaluronate is also a major component of skin, where Hyaluronate is involved in repairing tissue.
When skin is exposed to excessive UVB rays, Hyaluronate becomes inflamed (sunburn), and the cells in the dermis stop producing as much Hyaluronate and increase the rate of Hyaluronate degradation.
Hyaluronate degradation products then accumulate in the skin after UV exposure.

While Hyaluronate is abundant in extracellular matrices, Hyaluronate also contributes to tissue hydrodynamics, movement, and proliferation of cells and participates in a number of cell surface receptor interactions, notably those including Hyaluronate primary receptors, CD44 and RHAMM.
Upregulation of CD44 itself is widely accepted as a marker of cell activation in lymphocytes.

Hyaluronate's contribution to tumor growth may be due to Hyaluronate interaction with CD44.
Receptor CD44 participates in cell adhesion interactions required by tumor cells.

Although Hyaluronate binds to receptor CD44, there is evidence Hyaluronate degradation products transduce their inflammatory signal through toll-like receptor 2 (TLR2), TLR4, or both TLR2 and TLR4 in macrophages and dendritic cells.
TLR and Hyaluronate play a role in innate immunity.

There are limitations including the in vivo loss of Hyaluronate limiting the duration of effect.

Over the past 2 decades there was considerable evidence presented that unraveled the functional role of Hyaluronate in molecular mechanisms and indicated the potential role of Hyaluronate for the development of novel therapeutic strategies for many diseases.

Functions of Hyaluronate include the following: hydration, lubrication of joints, a space filling capacity, and the framework through which cells migrate.
The synthesis of Hyaluronate increases during tissue injury and wound healing and Hyaluronate regulates several aspects of tissue repair, including activation of inflammatory cells to enhance immune response and the response to injury of fibroblasts and epithelial cells.

Hyaluronate also provides the framework for blood vessel formation and fibroblast migration that may be involved in tumor progression.
The correlation of Hyaluronate levels on the cell surface of cancer cells with the aggressiveness of tumors has also been reported.

The size of Hyaluronate appears to be of critical importance for Hyaluronate various functions described above.
Hyaluronate of high molecular size, usually in excess of 1,000 kDa, is present in intact tissues and is antiangiogenic and immunosuppressive, whereas smaller polymers of Hyaluronate are distress signals and potent inducers of inflammation and angiogenesis.

Wound repair:
As a major component of the extracellular matrix, Hyaluronate has a key role in tissue regeneration, inflammation response, and angiogenesis, which are phases of wound repair.
As of 2023, however, reviews of Hyaluronate effect on healing for chronic wounds including burns, diabetic foot ulcers or surgical skin repairs show either insufficient evidence or only limited positive clinical research evidence.

There is also some limited evidence to suggest that Hyaluronate may be beneficial for ulcer healing and may help to a small degree with pain control.
Hyaluronate combines with water and swells to form a gel, making Hyaluronate useful in skin treatments as a dermal filler for facial wrinkles; Hyaluronate effect lasts for about 6 to 12 months, and treatment has regulatory approval from the US Food and Drug Administration.

Granulation:
Granulation tissue is the perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds.
Hyaluronate typically grows from the base of a wound and is able to fill wounds of almost any size Hyaluronate heals.

Hyaluronate is abundant in granulation tissue matrix.
A variety of cell functions that are essential for tissue repair may attribute to this Hyaluronate-rich network.

These functions include facilitation of cell migration into the provisional wound matrix, cell proliferation, and organization of the granulation tissue matrix.
Initiation of inflammation is crucial for the formation of granulation tissue; therefore, the pro-inflammatory role of Hyaluronate as discussed above also contributes to this stage of wound healing.

Cell migration:
Cell migration is essential for the formation of granulation tissue.
The early stage of granulation tissue is dominated by a Hyaluronate-rich extracellular matrix, which is regarded as a conducive environment for the migration of cells into this temporary wound matrix.

Hyaluronate provides an open hydrated matrix that facilitates cell migration, whereas, in the latter scenario, directed migration and control of related cell mechanisms are mediated via the specific cell interaction between Hyaluronate and cell surface Hyaluronate receptors.
Hyaluronate forms links with several protein kinases associated with cell locomotion, for example, extracellular signal-regulated kinase, focal adhesion kinase, and other non-receptor tyrosine kinases.

During fetal development, the migration path through which neural crest cells migrate is rich in Hyaluronate.
Hyaluronate is closely associated with the cell migration process in granulation tissue matrix, and studies show that cell movement can be inhibited, at least partially, by Hyaluronate degradation or blocking Hyaluronate receptor occupancy.

By providing the dynamic force to the cell, Hyaluronate synthesis has also been shown to associate with cell migration.
Basically, Hyaluronate is synthesized at the plasma membrane and released directly into the extracellular environment.
This may contribute to the hydrated microenvironment at sites of synthesis, and is essential for cell migration by facilitating cell detachment.

Skin healing:
Hyaluronate plays an important role in the normal epidermis.
Hyaluronate also has crucial functions in the reepithelization process due to several of Hyaluronate properties.
These include being an integral part of the extracellular matrix of basal keratinocytes, which are major constituents of the epidermis; Hyaluronate free-radical scavenging function, and Hyaluronate role in keratinocyte proliferation and migration.

In normal skin, Hyaluronate is found in relatively high concentrations in the basal layer of the epidermis where proliferating keratinocytes are found.
CD44 is collocated with Hyaluronate in the basal layer of epidermis where additionally Hyaluronate has been shown to be preferentially expressed on plasma membrane facing the Hyaluronate-rich matrix pouches.

Maintaining the extracellular space and providing an open, as well as hydrated, structure for the passage of nutrients are the main functions of Hyaluronate in epidermis.
A report found Hyaluronate content increases in the presence of retinoic acid (vitamin A).

The proposed effects of retinoic acid against skin photo-damage and photoaging may be correlated, at least in part, with an increase of skin Hyaluronate content, giving rise to increased tissue hydration.
Hyaluronate has been suggested that the free-radical scavenging property of Hyaluronate contributes to protection against solar radiation, supporting the role of CD44 acting as a Hyaluronate receptor in the epidermis.

Epidermal Hyaluronate also functions as a manipulator in the process of keratinocyte proliferation, which is essential in normal epidermal function, as well as during reepithelization in tissue repair.
In the wound healing process, Hyaluronate is expressed in the wound margin, in the connective tissue matrix, and collocating with CD44 expression in migrating keratinocytes.

Receptors of Hyaluronate:
There is a variety of proteins that bind Hyaluronate, called hyaladherins, which are widely distributed in the ECM, the cell surface, the cytoplasm and the nucleus.
Those that attach Hyaluronate to the cell surface constitute Hyaluronate receptors.

The most prominent among these receptors is the transmembrane glycoprotein “cluster of differentiation 44” (CD44) that occurs in many isoforms, which are Hyaluronatess of a single gene with variable exon expression.
CD44 is found on virtually all cells, except red blood cells, and regulates cell adhesion, migration, lymphocyte activation and homing, and cancer metastasis.

The receptor for Hyaluronate-mediated motility (RHAMM) is another major receptor for Hyaluronate, and Hyaluronate is expressed in various isoforms.
RHAMM is a functional receptor in many cell types, including endothelial cells88 and in smooth muscle cells from human pulmonary arteries37 and airways.

The interactions of Hyaluronate with RHAMM control cell growth and migration by a complex network of signal transduction events and interactions with the cytoskeleton.
Transforming growth factor (TGF)-β1, which is a potent stimulator of cell motility, elicits the synthesis and expression of RHAMM and Hyaluronate, and thus initiates locomotion.

Structure of Hyaluronate:
Hyaluronate is a polymer of disaccharides, which are composed of D-glucuronic acid and N-acetyl-D-glucosamine, linked via alternating β-(1→4) and β-(1→3) glycosidic bonds.
Hyaluronate can be 25,000 disaccharide repeats in length.

Polymers of Hyaluronate can range in size from 5,000 to 20,000,000 Da in vivo.
The average molecular weight in human synovial fluid is 3–4 million Da, and Hyaluronate purified from human umbilical cord is 3,140,000 Da; other sources mention average molecular weight of 7 million Da for synovial fluid.
Hyaluronate also contains silicon, ranging 350–1,900 μg/g depending on location in the organism.

Hyaluronate is energetically stable, in part because of the stereochemistry of Hyaluronate component disaccharides.
Bulky groups on each sugar molecule are in sterically favored positions, whereas the smaller hydrogens assume the less-favorable axial positions.

Hyaluronate in aqueous solutions self-associates to form transient clusters in solution.
While Hyaluronate is considered a polyelectrolyte polymer chain, Hyaluronate does not exhibit the polyelectrolyte peak, suggesting the absence of a characteristic length scale between the Hyaluronate molecules and the emergence of a fractal clustering, which is due to the strong solvation of these molecules.

Biological Synthesis:
Hyaluronate is synthesized by a class of integral membrane proteins called Hyaluronic acid synthases, of which vertebrates have three types: HAS1, HAS2, and HAS3.
These enzymes lengthen Hyaluronate by repeatedly adding D-glucuronic acid and N-acetyl-D-glucosamine to the nascent polysaccharide as Hyaluronate is extruded via ABC-transporter through the cell membrane into the extracellular space.
The term fasciacyte was coined to describe fibroblast-like cells that synthesize Hyaluronate.

Hyaluronate synthesis has been shown to be inhibited by 4-methylumbelliferone (hymecromone), a 7-hydroxy-4-methylcoumarin derivative.
This selective inhibition (without inhibiting other glycosaminoglycans) may prove useful in preventing metastasis of malignant tumor cells.
There is feedback inhibition of Hyaluronate synthesis by low-molecular-weight Hyaluronate (<500 kDa) at high concentrations, but stimulation by high-molecular-weight Hyaluronate (>500 kDa), when tested in cultured human synovial fibroblasts.

Bacillus subtilis recently has been genetically modified to culture a proprietary formula to yield Hyaluronates, in a patented process producing human-grade product.

Fasciacyte:
A fasciacyte is a type of biological cell that produces Hyaluronate-rich extracellular matrix and modulates the gliding of muscle fasciae.

Fasciacytes are fibroblast-like cells found in fasciae.
They are round-shaped with rounder nuclei and have less elongated cellular processes when compared with fibroblasts.
Fasciacytes are clustered along the upper and lower surfaces of a fascial layer.

Fasciacytes produce Hyaluronate, which regulates fascial gliding.

Biosynthetic Mechanism of Hyaluronate:
Hyaluronate is a linear glycosaminoglycan (GAG), an anionic, gel-like, polymer, found in the extracellular matrix of epithelial and connective tissues of vertebrates.
Hyaluronate is part of a family of structurally complex, linear, anionic polysaccharides.
The carboxylate groups present in the molecule make Hyaluronate negatively charged, therefore allowing for successful binding to water, and making Hyaluronate valuable to cosmetic and pharmaceutical products.

Hyaluronate consists of repeating β4-glucuronic acid (GlcUA)-β3-N-acetylglucosamine (GlcNAc) disaccharides, and is synthesized by Hyaluronate synthases (HAS), a class of integral membrane proteins that produce the well-defined, uniform chain lengths characteristic to Hyaluronate.
There are three existing types of HASs in vertebrates: HAS1, HAS2, HAS3; each of these contribute to elongation of the Hyaluronate polymer.

For an Hyaluronate capsule to be created, this enzyme must be present because Hyaluronate polymerizes UDP-sugar precursors into Hyaluronate.
Hyaluronate precursors are synthesized by first phosphorylating glucose by hexokinase, yielding glucose-6-phosphate, which is the main Hyaluronate precursor.

Then, two routes are taken to synthesize UDP-n-acetylglucosamine and UDP-glucuronic acid which both react to form Hyaluronate.
Glucose-6-phosphate gets converted to either fructose-6-phosphate with hasE (phosphoglucoisomerase), or glucose-1-phosphate using pgm (α -phosphoglucomutase), where those both undergo different sets of reactions.

UDP-glucuronic acid and UDP-n-acetylglucosamine get bound together to form Hyaluronate via hasA (Hyaluronate synthase).

Synthesis of UDP-glucuronic acid:
UDP-glucuronic acid is formed from hasC (UDP-glucose pyrophosphorylase) converting glucose-1-P into UDP-glucose, which then reacts with hasB (UDP-glucose dehydrogenase) to form UDP-glucuronic acid.

Synthesis of N-acetyl glucosamine:
The path forward from fructose-6-P utilizes glmS (amidotransferase) to form glucosamine-6-P.
Then, glmM (Mutase) reacts with Hyaluronate to form glucosamine-1-P.
hasD (acetyltransferase) converts this into n-acetylglucosamine-1-P, and finally, hasD (pyrophosphorylase) converts Hyaluronate into UDP-n-acetylglucosamine.

Final step: Two disaccharides form Hyaluronate:
UDP-glucuronic acid and UDP-n-acetylglucosamine get bound together to form Hyaluronate via hasA (Hyaluronate synthase), completing the synthesis.

Chemistry and Physicochemical Properties of Hyaluronate:
Hyaluronate is a non-sulphated GAG and is composed of repeating polymeric disaccharides of D-glucuronic acid and N-acetyl-D-glucosamine linked by a glucuronidic β (1→3) bond.
In aqueous solutions Hyaluronate forms specific stable tertiary structures.

Despite the simplicity in Hyaluronate composition, without variations in Hyaluronate sugar composition or without branching points, Hyaluronate has a variety of physicochemical properties.
Hyaluronate polymers occur in a vast number of configurations and shapes, depending on their size, salt concentration, pH, and associated cations.

Unlike other GAG, Hyaluronate is not covalently attached to a protein core, but Hyaluronate may form aggregates with proteoglycans.
Hyaluronate encompasses a large volume of water giving solutions high viscosity, even at low concentrations.

Degradation of Hyaluronate:
Hyaluronate can be degraded by a family of enzymes called hyaluronidases.
In humans, there are at least seven types of hyaluronidase-like enzymes, several of which are tumor suppressors.

The degradation products of Hyaluronate, the oligosaccharides and very low-molecular-weight Hyaluronate, exhibit pro-angiogenic properties.
In addition, recent studies showed Hyaluronate fragments, not the native high-molecular weight molecule, can induce inflammatory responses in macrophages and dendritic cells in tissue injury and in skin transplant.

Hyaluronate can also be degraded via non-enzymatic reactions.
These include acidic and alkaline hydrolysis, ultrasonic disintegration, thermal decomposition, and degradation by oxidants.

Tissue and cell distribution of Hyaluronate:
Hyaluronate is widely distributed, from prokaryotic to eukaryotic cells.
In humans, Hyaluronate is most abundant in the skin accounting for 50% of the total body Hyaluronate the vitreous of the eye the umbilical cord and synovial fluid but Hyaluronate is also present in all tissues and fluids of the body, such as skeletal tissues heart valves the lung the aorta the prostate tunica albuginea, corpora cavernosa and corpus spongiosum of the penis.
Hyaluronate is produced primarily by mesenchymal cells but also by other cell types.

Etymology of Hyaluronate:
Hyaluronate is derived from hyalos (Greek for vitreous, meaning ‘glass-like’) and uronic acid because Hyaluronate was first isolated from the vitreous humour and possesses a high uronic acid content.
The term hyaluronate refers to the conjugate base of Hyaluronan.
Since the molecule typically exists in vivo in Hyaluronic acid polyanionic form, Hyaluronate is most commonly referred to as Hyaluronate.

History of Hyaluronate:
Hyaluronate was first obtained by Karl Meyer and John Palmer in 1934 from the vitreous body in a cow's eye.
The first Hyaluronate biomedical product, Healon, was developed in the 1970s and 1980s by Pharmacia, and approved for use in eye surgery (i.e., corneal transplantation, cataract surgery, glaucoma surgery, and surgery to repair retinal detachment).
Other biomedical companies also produce brands of Hyaluronate for ophthalmic surgery.

Native Hyaluronate has a relatively short half-life (shown in rabbits) so various manufacturing techniques have been deployed to extend the length of the chain and stabilise the molecule for Hyaluronate use in medical applications.
The introduction of protein-based cross-links, the introduction of free-radical scavenging molecules such as sorbitol, and minimal stabilisation of the Hyaluronate chains through chemical agents such as NASHA (non-animal stabilised Hyaluronate) are all techniques that have been used to preserve Hyaluronate shelf life.

In the late 1970s, intraocular lens implantation was often followed by severe corneal edema, due to endothelial cell damage during the surgery.
Hyaluronate was evident that a viscous, clear, physiologic lubricant to prevent such scraping of the endothelial cells was needed.

The name "Hyaluronate" is also used for a salt.

Research of Hyaluronate:
Due to Hyaluronate high biocompatibility and Hyaluronate common presence in the extracellular matrix of tissues, Hyaluronate is used as a biomaterial scaffold in tissue engineering research.
In particular, research groups have found Hyaluronate's properties for tissue engineering and regenerative medicine may be improved with cross-linking, producing a hydrogel.

Crosslinking may allow a desired shape, as well as to deliver therapeutic molecules into a host.
Hyaluronate can be crosslinked by attaching thiols (see thiomers)(trade names: Extracel, HyStem), hexadecylamides (trade name: Hymovis), and tyramines (trade name: Corgel).
Hyaluronate can also be crosslinked directly with formaldehyde (trade name: Hylan-A) or with divinylsulfone (trade name: Hylan-B).

Due to Hyaluronate ability to regulate angiogenesis by stimulating endothelial cells to proliferate in vitro, Hyaluronate can be used to create hydrogels to study vascular morphogenesis.

Identifiers of Hyaluronate:
CAS Number: 
9004-61-9
31799-91-4 (potassium salt)
9067-32-7 (sodium salt)
ChEBI: CHEBI:16336
ECHA InfoCard: 100.029.695
EC Number: 232-678-0
UNII: S270N0TRQY
CompTox Dashboard (EPA): DTXSID90925319 DTXSID7046750, DTXSID90925319

EC / List no.: 232-678-0
CAS no.: 9004-61-9

CAS No.: 9004-61-9
Chemical Name: Hyaluronan
CBNumber: CB1176690
Molecular Formula: C14H22NNaO11
Molecular Weight: 403.31
MDL Number: MFCD00131348

Properties of Hyaluronate:
Chemical formula: (C14H21NO11)n
Solubility in water: Soluble (sodium salt)

storage temp.: −20°C
solubility: H2O: 5 mg/mL, clear, colorless
form: Lyophilized Powder
color: White
Odor: Odorless
Water Solubility: Soluble in water.
InChIKey: MAKUBRYLFHZREJ-IUPJJCKZNA-M
SMILES: [C@@H]1(O[C@H]2[C@H](O)[C@H]([C@H](O)O[C@@H]2C(=O)[O-])O)O[C@H](CO)[C@@H](O)C[C@H]1NC(=O)C.[Na+] |&1:0,2,3,5,6,9,15,18,21,r|
LogP: -6.623 (est)
CAS DataBase Reference: 9004-61-9
EWG's Food Scores: 1
FDA UNII: HYALURONIC ACID (NON-ANIMAL STABILIZED) (B7SG5YV2SI)
HYALURONIC ACID (S270N0TRQY)
NCI Drug Dictionary: hyaluronic acid
ATC code: D03AX05,M09AX01,R01AX09,S01KA01,S01KA51
EPA Substance Registry System: Hyaluronic acid (9004-61-9)

Molecular Weight: 425.38 g/mol
XLogP3-AA: -3.4
Hydrogen Bond Donor Count: 6
Hydrogen Bond Acceptor Count: 12
Rotatable Bond Count: 7
Exact Mass: 425.15332530 g/mol
Monoisotopic Mass: 425.15332530 g/mol
Topological Polar Surface Area: 194Ų
Heavy Atom Count: 29
Complexity: 576
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 10
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Related compound of Hyaluronate:
D-Glucuronic acid and N-acetyl-D-glucosamine (monomers)

Names of Hyaluronate:

Regulatory process names:
Hyaluronic acid
Hyaluronic acid

IUPAC names:
(2S,3S,4S,5R,6R)-6-[(2S,3R,5S,6R)-3-acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
(2Z,4S,4aS,5aR,12aS)-2-[amino(hydroxy)methylidene]-4,
[-4)GlcA(β1-3)GlcNAc(β1-]n
Hyaluronic acid
(1→4)-(2-Acetamido-2-deoxy-D-gluco)-(1→3)-D-glucuronoglycan

Systematic IUPAC name:
Poly{[(2S,3R,4R,5S,6R)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxane-2,4-diyl]oxy[(2R,3R,4R,5S,6S)-6-carboxy-3,4-dihydroxyoxane-2,5-diyl]oxy}

Other identifier:
9004-61-9