Sodium hyaluronate
Encyclopedia
Sodium hyaluronate is the sodium
salt
of hyaluronan
. The name hyaluronic acid is derived from the Greek
word ύαλος (hyalos) meaning vitreous, and uronic acid
as it was first isolated from the vitreous humour
in the eye and possesses a high uronic acid content. The term hyaluronate also refers to the conjugate base of hyaluronic acid. Because the molecule typically exists in vivo in its polyanionic form, it is most commonly referred to as hyaluronan. It is a visco-elastic
polymer
normally found in the aqueous
and vitreous humour.
Sodium hyaluronate is a viscous solution consisting of a high molecular weight (500,000-730,000 daltons
) fraction of purified natural sodium hyaluronate in buffered physiological sodium chloride. Hyaluronic acid is a natural complex sugar of the glycosaminoglycan
family and is a long-chain polymer containing repeating disaccharide units of Na-glucuronate-N-acetylglucosamine. Sodium hyaluronate occurs naturally on the corneal endothelium
, bound to specific receptors for which it has a high affinity.
Chemically, sodium hyaluronate referred to as Sodium (2S,3S,4R,5R,6R)-3- [(2S,3R,4R,5S,6R)-3-acetamido-4-[(2R,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4,5-dihydroxyoxane-2-carboxylic acid. It is produced by biological culture of genetic transformed bacteria.
into the knee
, increasing the viscosity
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 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 analgesic
s. It may also be effective when used with other joints.
Sodium hyaluronate may also be used in plastic surgery
to reduce wrinkles on the face or as a filler in other parts of the body. It may be used in ophthalmology
to assist in the extraction of cataract
s, the implantation of intraocular lens
es, corneal transplants, glaucoma
filtration, retinal
attachment and in the treatment of dry eyes.
Sodium hyaluronate is also used to coat the bladder lining in treating interstitial cystitis
.
When used in ophthalmological procedures, sodium hyaluronate may cause postoperative inflammation
, corneal edema
or decompensation
, and short-term increases in intraocular pressure
.
and is thought to play an important role in modulating the interactions between adjacent tissues. Sodium hyaluronate is a polysaccharide
which is distributed widely in the extracellular matrix
of connective tissue in man. It forms a viscoelastic solution in water which makes it suitable for aqueous
and vitreous humor
in ophthalmic surgery
. 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
for tissues. This viscoelasticity enables maintenance of a deep chamber during surgical manipulation since the solution does not flow out of the open anterior chamber. 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. Sodium hyaluronate is being used intra-articularly to treat osteoarthritis
.
agent with viscoelastic properties that is used in joint
s to supplement synovial fluid
.
.
in Market include (alphabetically):
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
salt
Salt
In chemistry, salts are ionic compounds that result from the neutralization reaction of an acid and a base. They are composed of cations and anions so that the product is electrically neutral...
of hyaluronan
Hyaluronan
Hyaluronan is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues...
. The name hyaluronic acid is derived from the Greek
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
word ύαλος (hyalos) meaning vitreous, and uronic acid
Uronic acid
thumb|300px|The [[Fischer projection]]s of [[glucose]] and [[glucuronic acid]]. Glucose's terminal carbon's hydroxyl group has been oxidized to a [[carboxylic acid]]....
as it was first isolated from the vitreous humour
Vitreous humour
The vitreous humour or vitreous humor is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates...
in the eye and possesses a high uronic acid content. The term hyaluronate also refers to the conjugate base of hyaluronic acid. Because the molecule typically exists in vivo in its polyanionic form, it is most commonly referred to as hyaluronan. It is a visco-elastic
Viscoelasticity
Viscoelasticity is the property of materials that exhibit both viscous and elastic characteristics when undergoing deformation. Viscous materials, like honey, resist shear flow and strain linearly with time when a stress is applied. Elastic materials strain instantaneously when stretched and just...
polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
normally found in the aqueous
Aqueous humour
The aqueous humour is a clear, gelatinous fluid similar to plasma, but containing low-protein concentrations. It is secreted from the ciliary epithelium, a structure supporting the lens. It is located in the space between the lens and the cornea...
and vitreous humour.
Sodium hyaluronate is a viscous solution consisting of a high molecular weight (500,000-730,000 daltons
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
) fraction of purified natural sodium hyaluronate in buffered physiological sodium chloride. Hyaluronic acid is a natural complex sugar of the glycosaminoglycan
Glycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...
family and is a long-chain polymer containing repeating disaccharide units of Na-glucuronate-N-acetylglucosamine. Sodium hyaluronate occurs naturally on the corneal endothelium
Corneal endothelium
The corneal endothelium is a single layer of cells on the inner surface of the cornea. It faces the chamber formed between the cornea and the iris....
, bound to specific receptors for which it has a high affinity.
Chemically, sodium hyaluronate referred to as Sodium (2S,3S,4R,5R,6R)-3- [(2S,3R,4R,5S,6R)-3-acetamido-4-[(2R,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4,5-dihydroxyoxane-2-carboxylic acid. It is produced by biological culture of genetic transformed bacteria.
Medical uses
Sodium hyaluronate is used as a viscosupplement, administered through a series of injectionsInjection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
into the knee
Knee
The knee joint joins the thigh with the leg and consists of two articulations: one between the fibula and tibia, and one between the femur and patella. It is the largest joint in the human body and is very complicated. The knee is a mobile trocho-ginglymus , which permits flexion and extension as...
, increasing the viscosity
Viscosity
Viscosity is a measure of the resistance of a fluid which is being deformed by either shear or tensile stress. In everyday terms , viscosity is "thickness" or "internal friction". Thus, water is "thin", having a lower viscosity, while honey is "thick", having a higher viscosity...
of the synovial fluid
Synovial fluid
Synovial fluid is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its yolk-like consistency , the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement.-Overview:The inner membrane of synovial joints...
, which helps lubricate, cushion and reduce pain in the joint. It is generally used as a last resort before surgery and provides symptomatic 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 analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
s. It may also be effective when used with other joints.
Sodium hyaluronate may also be used in plastic surgery
Plastic surgery
Plastic surgery is a medical specialty concerned with the correction or restoration of form and function. Though cosmetic or aesthetic surgery is the best-known kind of plastic surgery, most plastic surgery is not cosmetic: plastic surgery includes many types of reconstructive surgery, hand...
to reduce wrinkles on the face or as a filler in other parts of the body. It may be used in ophthalmology
Ophthalmology
Ophthalmology is the branch of medicine that deals with the anatomy, physiology and diseases of the eye. An ophthalmologist is a specialist in medical and surgical eye problems...
to assist in the extraction of cataract
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
s, the implantation of intraocular lens
Intraocular lens
An intraocular lens is an implanted lens in the eye, usually replacing the existing crystalline lens because it has been clouded over by a cataract, or as a form of refractive surgery to change the eye's optical power. It usually consists of a small plastic lens with plastic side struts, called...
es, corneal transplants, glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
filtration, retinal
Retinal
Retinal, also called retinaldehyde or vitamin A aldehyde, is one of the many forms of vitamin A . Retinal is a polyene chromophore, and bound to proteins called opsins, is the chemical basis of animal vision...
attachment and in the treatment of dry eyes.
Sodium hyaluronate is also used to coat the bladder lining in treating interstitial cystitis
Interstitial cystitis
Interstitial cystitis or bladder pain syndrome is a chronic, oftentimes severely debilitating disease of the urinary bladder...
.
Contraindications
Sodium hyaluronate is contraindicated for people who are sensitive to hyaluronate preparations, or when there are infections or skin disease at the injection site.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
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
, corneal edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
or decompensation
Decompensation
In medicine, decompensation is the functional deterioration of a previously working structure or system. Decompensation may occur due to fatigue, stress, illness, or old age. When a system is "compensated," it is able to function despite stressors or defects. Decompensation describes an inability...
, and short-term increases in intraocular pressure
Intraocular pressure
Intraocular pressure 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 from glaucoma...
.
Mechanism of action
Sodium hyaluronate functions as a tissue lubricantLubricant
A lubricant is a substance introduced to reduce friction between moving surfaces. It may also have the function of transporting foreign particles and of distributing heat...
and is thought to play an important role in modulating the interactions between adjacent tissues. Sodium hyaluronate is a polysaccharide
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
which is distributed widely in the extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
of connective tissue in man. It forms a viscoelastic solution in water which makes it suitable for aqueous
Aqueous solution
An aqueous solution is a solution in which the solvent is water. It is usually shown in chemical equations by appending aq to the relevant formula, such as NaCl. The word aqueous means pertaining to, related to, similar to, or dissolved in water...
and vitreous humor
Vitreous humour
The vitreous humour or vitreous humor is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates...
in ophthalmic surgery
Eye surgery
Eye surgery, also known as orogolomistician surgery or ocular surgery, is surgery performed on the eye or its adnexa, typically by an ophthalmologist.-Preparation and precautions:...
. 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 solution
A buffer solution is an aqueous solution consisting of a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid. It has the property that the pH of the solution changes very little when a small amount of strong acid or base is added to it. Buffer solutions are used as a...
for tissues. This viscoelasticity enables maintenance of a deep chamber during surgical manipulation since the solution does not flow out of the open anterior chamber. 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. Sodium hyaluronate is being used intra-articularly to treat osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
.
Physical and chemical properties
Sodium hyaluronate is an ophthalmicOphthalmology
Ophthalmology is the branch of medicine that deals with the anatomy, physiology and diseases of the eye. An ophthalmologist is a specialist in medical and surgical eye problems...
agent with viscoelastic properties that is used in joint
Joint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
s to supplement synovial fluid
Synovial fluid
Synovial fluid is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its yolk-like consistency , the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement.-Overview:The inner membrane of synovial joints...
.
Pharmacokinetics
Sodium hyaluronate is absorbed and diffuses slowly out of the injection site. It is eliminated via the canal of SchlemmSchlemm's canal
Schlemm's canal, also known as canal of Schlemm or the scleral venous sinus, is a circular channel in the eye that collects aqueous humor from the anterior chamber and delivers it into the bloodstream via the anterior ciliary veins....
.
History
Sodium hyaluronate hyaluronan started to be in use to treat osteoarthritis of the knee in year 1997 with the product Hyalart/Fidia Italy, in intra-articular injections.Economics
Brand names of Sodium hyaluronateSodium hyaluronate
Sodium hyaluronate is the sodium salt of hyaluronan. The name hyaluronic acid is derived from the Greek word ύαλος meaning vitreous, and uronic acid as it was first isolated from the vitreous humour in the eye and possesses a high uronic acid content. The term hyaluronate also refers to the...
in Market include (alphabetically):
- AMO Vitrax (ocular)
- AMVISIC Plus (ocular)
- CYSTISTAR, Healon (ocular)
- HYLO-COMOD (Eye Drop)
- EUFLEXXA, Bio Technology General (Israel)-Meditrina SA (Rx articular), Molecular weight: 2,400,000-3,600,000 Daltons
- GONILERT/Verisfield (UK) (Rx/articular). Molecular weight:1,800,000-2,000,000 Daltons
- HYALGAN (USA)(Medcical Device/Rx articular)
- HYALART-Fidia (Italy)(Rx/articular), Molecular weight: 1,800,000-2,000,000 Daltons
- MONOVISC-Anika (USA)(MedicalDevice/articular)
- VISCURE-Cube (UK)(Rx/articular), Molecular weight:1,800,000-2,000,000 Daltons
- YARDEL-Libytec (Impfstoffwerk Dessau-Tornau/Germany,(Rx/articular), Molecular weight:1,800,000-2,000,000 Daltons