Sodium hyaluronate is the

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

salt of hyaluronic acid, a

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...

found in various connective tissue of humans.

Chemistry

Sodium hyaluronate is the

salt of hyaluronic acid. It is a

and long-chain

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

disaccharide A disaccharide (also called a double sugar or ''biose'') is the sugar formed when two monosaccharides are joined by glycosidic linkage. Like monosaccharides, disaccharides are simple sugars soluble in water. Three common examples are sucrose, la ...

units of Na-glucuronate-N-acetylglucosamine. It can bind to specific receptors for which it has a high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

. The polyanionic form, commonly referred to as hyaluronan, is a

visco-elastic In materials science and continuum mechanics, viscoelasticity is the property of materials that exhibit both viscous and elastic characteristics when undergoing deformation. Viscous materials, like water, resist shear flow and strain linearly ...

polymer found in the

aqueous An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, or sodium chloride (NaCl), in water would be re ...

and

vitreous humour The vitreous body (''vitreous'' meaning "glass-like"; , ) is the clear gel that fills the space between the lens and the retina of the eyeball (the vitreous chamber) in humans and other vertebrates. It is often referred to as the vitreous humor ...

of the eye and in the fluid of articulating

joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...

Natural occurrence

Sodium hyaluronate, as hyaluronic acid, is distributed widely in the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...

of mammalian connective,

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...

, and

neural tissue Nervous tissue, also called neural tissue, is the main tissue (biology), tissue component of the nervous system. The nervous system regulates and controls body functions and activity. It consists of two parts: the central nervous system (CNS) com ...

s, as well as the

corneal endothelium The corneal endothelium is a single layer of endothelial cells on the inner surface of the cornea. It faces the chamber formed between the cornea and the iris. The corneal endothelium are specialized, flattened, mitochondria-rich cells that li ...

Mechanism of action

Sodium hyaluronate functions as a tissue lubricant and is thought to play an important role in modulating the interactions between adjacent tissues. It forms a viscoelastic solution in water. Mechanical protection for tissues (iris, retina) and cell layers (corneal, endothelium, and epithelium) are provided by the high viscosity of the solution. Elasticity of the solution assists in absorbing mechanical stress and providing a protective

buffer Buffer may refer to: Science * Buffer gas, an inert or nonflammable gas * Buffer solution, a solution used to prevent changes in pH * Buffering agent, the weak acid or base in a buffer solution * Lysis buffer, in cell biology * Metal ion buffer * ...

for tissues. In facilitating wound healing, it is thought that it acts as a protective transport vehicle, taking peptide growth factors and other structural proteins to a site of action. It is then enzymatically degraded and active proteins are released to promote tissue repair.

Pharmacokinetics

Sodium hyaluronate is cleared within hours of injection but appears to have residual effects on contacted cells. In the eye it is eliminated via the canal of Schlemm.

Adverse effects

Adverse effects are relatively rare when used to treat the joints. When used in ophthalmological procedures, sodium hyaluronate may cause postoperative

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

, corneal edema or

decompensation In medicine, decompensation is the functional deterioration of a structure or system that had been previously working with the help of compensation. Decompensation may occur due to fatigue, stress, illness, or old age. When a system is "compensate ...

, and short-term increases in

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...

Medical uses

Intra-articular injection

It is used to treat knee pain in patients with

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

who have not received relief from other treatments. It is injected into the joint capsule, to act as both a shock absorber and a lubricant for the joint. Thus sodium hyaluronate is used as a viscosupplement, administered through a series of injections into the knee, increasing the

viscosity The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water. Viscosity quantifies the inte ...

of the synovial fluid, which helps lubricate, cushion and reduce pain in the joint. It is generally used as a last resort before surgery and provides

symptomatic Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...

relief, by recovering the viscoelasticity of the articular fluid, and by stimulating new production from synovial fluid. Use of sodium hyaluronate may reduce the need for joint replacement. Injections appear to increase in effectiveness over the course of four weeks, reaching a peak at eight weeks and retaining some effectiveness at six months, with greater benefit for osteoarthritis than oral analgesics. It may also be effective when used with the ankle joint.

Intraocular viscoelastic injection

It is used as an aid in

ophthalmic surgery Eye surgery, also known as ophthalmic or ocular surgery, is surgery performed on the eye or its adnexa, by an ophthalmologist or sometimes, an optometrist. Eye surgery is synonymous with ophthalmology. The eye is a very fragile organ, and requ ...

acting as

and

vitreous humor The vitreous body (''vitreous'' meaning "glass-like"; , ) is the clear gel that fills the space between the lens and the retina of the eyeball (the vitreous chamber) in humans and other vertebrates. It is often referred to as the vitreous humor ...

, e.g. in

cataract extraction Cataract surgery, also called lens replacement surgery, is the removal of the natural lens of the eye (also called "crystalline lens") that has developed an opacification, which is referred to as a cataract, and its replacement with an intraoc ...

(intra- and extracapsular),

intraocular lens Intraocular lens (IOL) is a lens (optics), lens implanted in the human eye, eye as part of a treatment for cataracts or myopia. If the natural lens is left in the eye, the IOL is known as Phakic intraocular lens, phakic, otherwise it is a pseudop ...

implantation, corneal transplant,

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

filtration, and retina attachment surgery and in the treatment of dry eyes. In surgical procedures in the anterior segment of eyeball, instillation of sodium hyaluronate its viscoelasticity enables maintenance of a deep chamber during surgical manipulation since the solution does not flow out of the open anterior chamber, allowing for efficient manipulation with less trauma to the

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical ...

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...

and other surrounding tissues. Its viscoelasticity also helps to push back the vitreous face and prevent formation of a postoperative flat chamber. In posterior segment surgery, sodium hyaluronate serves as a surgical aid to gently separate, maneuver, and hold tissues. It creates a clear field of vision, facilitating intra-operative and post-operative inspection of the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

and photocoagulation.

Skin injections in plastic surgery

Sodium hyaluronate is injected to reduce

wrinkle A wrinkle, also known as a rhytid, is a fold, ridge or crease in an otherwise smooth surface, such as on skin or fabric. Skin wrinkles typically appear as a result of ageing processes such as glycation, habitual sleeping positions, loss of ...

s on the face. As of 2017, the FDA had approved 13 hyaluronate preparations as so called dermal fillers. They are also used as a filler of lips or in other parts of the body, though not FDA approved. The filling effect is temporary and lasts for about six months or longer in most people.

Topical application

Topically applied sodium hyaluronate can facilitate the absorption of biomacromolecules, i.e. pharmaceuticals, and function like a nanocarrier. Its effects on skin depend on the hyaluronate formulation and skin health: In barrier-deficient skin it restricted the delivery of biomacromolecules to the stratum corneum and viable epidermis. In normal skin, low-molecular weight hyaluronate (5 kDa) enhanced penetration into the epidermis. Transepidermal water loss increased by 55.5% with low-molecular weight, and was reduced by 28% with crosslinked resilient, and by 16% with HMW. The addition to skin creams became popular in the second millennium. Its efficacy against wrinkles has not been tested in clinical trials. Dry, scaly skin, such as that caused by atopic dermatitis, may be treated with lotion or another skin product containing sodium hyaluronate as its active ingredient. After instillation into the lung, higher molecular weight hyaluronate appears to persist longer in the lung but if > 215 kD there was poor lung penetration and mucociliary clearance. Hyaluronate could allow access to lymph nodes draining the pulmonary bed.

Intravesical instillation

Sodium hyaluronate can be instilled into the bladder for the treatment of various forms of

cystitis A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

and associated bladder pain, by replenishing the

layer of the bladder urothelium.

Contraindications

Sodium hyaluronate has a very low incidence of side effects, however it is contraindicated in people who are sensitive to

hyaluronate Hyaluronic acid (; abbreviated HA; conjugate base hyaluronate), also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycan ...

preparations. If being administered as an intra-articular injection, it should not be given when there are infections or skin disease at the injection site.

History

In the late 1970s and early 1980s the material was used with the brand names of Hylartin and Hylartin Vetused in human and veterinary clinical trials (race horses) to treat osteoarthritis. The first commercially sold sodium hyaluronate had been developed by Endre Alexander Balazs under the brand name of Healon, manufactured by Pharmacia AB in Sweden in 1980. In 1986, sodium hyaluronate was used as an intra-articular injection to treat osteoarthritis of the knee with the product Hyalart/Hyalgan by Fidia of Italy.

References

{{DEFAULTSORT:Sodium Hyaluronate Glycosaminoglycans Organic sodium salts