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Sodium hyaluronate is the sodium salt of hyaluronic acid, a glycosaminoglycan found in various connective tissue of humans.
Sodium hyaluronate is the sodium salt of hyaluronic acid. It is a glycosaminoglycan and long-chain polymer of disaccharide units of Na-glucuronate-N-acetylglucosamine. It can bind to specific receptors for which it has a high affinity.
The polyanionic form, commonly referred to as hyaluronan, is a visco-elastic polymer found in the aqueous and vitreous humour of the eye and in the fluid of articulating joints.
Sodium hyaluronate, as hyaluronic acid, is distributed widely in the extracellular matrix of mammalian connective, epithelial, and neural tissues, as well as the corneal endothelium.
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 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. [1]
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.[ citation needed ]
Adverse effects are relatively rare when used to treat the joints. [2]
When used in ophthalmological procedures, sodium hyaluronate may cause postoperative inflammation, corneal edema or decompensation, and short-term increases in intraocular pressure.[ citation needed ]
It is used to treat knee pain in patients with osteoarthritis 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. [3] [4] [5] Thus sodium hyaluronate is used as a viscosupplement, administered through a series of injections into the knee, increasing the viscosity of the synovial fluid, which helps lubricate, cushion and reduce pain in the joint. [6] It is generally used as a last resort before surgery [7] and provides symptomatic relief, by recovering the viscoelasticity of the articular fluid, and by stimulating new production of synovial fluid. [2] Use of sodium hyaluronate may reduce the need for joint replacement. [8] 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. [9] It may also be effective when used with the ankle joint. [10]
It is used as an aid in ophthalmic surgery acting as aqueous and vitreous humor, e.g. in cataract extraction (intra- and extracapsular), intraocular lens implantation, corneal transplant, glaucoma filtration, and retina attachment surgery and in the treatment of dry eyes. [11] 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 corneal endothelium 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 and photocoagulation. [12]
Sodium hyaluronate is injected to reduce wrinkles on the face. As of 2017, the FDA had approved 13 hyaluronate preparations as so called dermal fillers. [13] They are also used as a filler of lips or in other parts of the body, though not FDA approved. [14] The filling effect is temporary and lasts for about six months or longer in most people. [15]
Topically applied sodium hyaluronate can facilitate the absorption of biomacromolecules, i.e. pharmaceuticals, and function like a nanocarrier. [16] 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. [17]
Transepidermal water loss increased by 55.5% with low-molecular weight, and was reduced by 28% with crosslinked resilient, and by 16% with HMW. [18] Its efficacy against wrinkles has not been tested in clinical trials. [19]
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. [20]
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. [21]
Sodium hyaluronate can be instilled into the bladder for the treatment of various forms of cystitis and associated bladder pain, by replenishing the glycosaminoglycan layer of the bladder urothelium. [22] [23]
Sodium hyaluronate has a very low incidence of side effects, however it is contraindicated in people who are sensitive to hyaluronate 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. [24] [25]
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. [26] 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. [27]
Cartilage is a resilient and smooth type of connective tissue. It is a semi-transparent and non-porous type of tissue. It is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck and the bronchial tubes, and the intervertebral discs. In other taxa, such as chondrichthyans, but also in cyclostomes, it may constitute a much greater proportion of the skeleton. It is not as hard and rigid as bone, but it is much stiffer and much less flexible than muscle. The matrix of cartilage is made up of glycosaminoglycans, proteoglycans, collagen fibers and, sometimes, elastin. It usually grows quicker than bone.
Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone. It is believed to be the fourth leading cause of disability in the world, affecting 1 in 7 adults in the United States alone. The most common symptoms are joint pain and stiffness. Usually the symptoms progress slowly over years. Other symptoms may include joint swelling, decreased range of motion, and, when the back is affected, weakness or numbness of the arms and legs. The most commonly involved joints are the two near the ends of the fingers and the joint at the base of the thumbs, the knee and hip joints, and the joints of the neck and lower back. The symptoms can interfere with work and normal daily activities. Unlike some other types of arthritis, only the joints, not internal organs, are affected.
Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units. The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case of the sulfated glycosaminoglycan keratan, where, in place of the uronic sugar there is a galactose unit. GAGs are found in vertebrates, invertebrates and bacteria. Because GAGs are highly polar molecules and attract water; the body uses them as lubricants or shock absorbers.
Synovial fluid, also called synovia,[help 1] is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement. Synovial fluid is a small component of the transcellular fluid component of extracellular fluid.
Hyaluronidases are a family of enzymes that catalyse the degradation of hyaluronic acid. Karl Meyer classified these enzymes in 1971, into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyaluronidases are two classes of eukaryotic endoglycosidase hydrolases and a prokaryotic lyase-type of glycosidase.
Hyaluronic acid, also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans as it is non-sulfated, forms in the plasma membrane instead of the Golgi apparatus, and can be very large: human synovial HA averages about 7 million Da per molecule, or about 20,000 disaccharide monomers, while other sources mention 3–4 million Da.
In medicine, a joint injection is a procedure used in the treatment of inflammatory joint conditions, such as rheumatoid arthritis, psoriatic arthritis, gout, tendinitis, bursitis, Carpal Tunnel Syndrome, and occasionally osteoarthritis. A hypodermic needle is injected into the affected joint where it delivers a dose of any one of many anti-inflammatory agents, the most common of which are corticosteroids. Hyaluronic acid, because of its high viscosity, is sometimes used to replace bursa fluids. The technique may be used to also withdraw excess fluid from the joint.
Pentosan polysulfate, sold under the brand name Elmiron among others, is a medication used for the treatment of interstitial cystitis. It was approved for medical use in the United States in 1996.
Articular cartilage, most notably that which is found in the knee joint, is generally characterized by very low friction, high wear resistance, and poor regenerative qualities. It is responsible for much of the compressive resistance and load bearing qualities of the knee joint and, without it, walking is painful to impossible. Osteoarthritis is a common condition of cartilage failure that can lead to limited range of motion, bone damage and invariably, pain. Due to a combination of acute stress and chronic fatigue, osteoarthritis directly manifests itself in a wearing away of the articular surface and, in extreme cases, bone can be exposed in the joint. Some additional examples of cartilage failure mechanisms include cellular matrix linkage rupture, chondrocyte protein synthesis inhibition, and chondrocyte apoptosis. There are several different repair options available for cartilage damage or failure.
Heparinoids are glycosaminoglycans which are chemically and pharmacologically related to heparin. They include oligosaccharides and sulfated polysaccharides of plant, animal, or synthetic origin. Multiple scientific studies have been conducted on heparinoids.
Articular cartilage repair treatment involves the repair of the surface of the articular joint's hyaline cartilage, though these solutions do not perfectly restore the articular cartilage. These treatments have been shown to have positive results for patients who have articular cartilage damage. They can provide some measure of pain relief, while slowing down the accumulation of damage, or delaying the need for joint replacement surgery.
Autologous chondrocyte implantation is a biomedical treatment that repairs damages in articular cartilage. ACI provides pain relief while at the same time slowing down the progression or considerably delaying partial or total joint replacement surgery. The goal of ACI is to allow people suffering from articular cartilage damage to return to their old lifestyle; regaining mobility, going back to work and even practicing sports again.
Mesenchymal stem cells (MSCs) are multipotent cells found in multiple human adult tissues, including bone marrow, synovial tissues, and adipose tissues. Since they are derived from the mesoderm, they have been shown to differentiate into bone, cartilage, muscle, and adipose tissue. MSCs from embryonic sources have shown promise scientifically while creating significant controversy. As a result, many researchers have focused on adult stem cells, or stem cells isolated from adult humans that can be transplanted into damaged tissue.
Arthritis of the knee is typically a particularly debilitating form of arthritis. The knee may become affected by almost any form of arthritis.
Gene therapy for osteoarthritis is the application of gene therapy to treat osteoarthritis (OA). Unlike pharmacological treatments which are administered locally or systemically as a series of interventions, gene therapy aims to establish sustained therapeutic effect after a single, local injection.
Injectable filler is a soft tissue filler injected into the skin at different depths to help fill in facial wrinkles, provide facial volume, and augment facial features: restoring a smoother appearance. Most of these wrinkle fillers are temporary because they are eventually absorbed by the body. Most dermal fillers today consist of hyaluronic acid, a naturally occurring polysaccharide that is present in skin and cartilage. Some people may need more than one injection to achieve the wrinkle-smoothing effect. The effect lasts for about six months or longer. Successful results depend on health of the skin, skill of the health care provider, and type of filler used. Regardless of material filler duration is highly dependent on amount of activity in the region where it is injected. Exercise and high intensity activities such as manual labor can stimulate blood flow and shorten the lifespan of fillers.
The treatment of equine lameness is a complex subject. Lameness in horses has a variety of causes, and treatment must be tailored to the type and degree of injury, as well as the financial capabilities of the owner. Treatment may be applied locally, systemically, or intralesionally, and the strategy for treatment may change as healing progresses. The end goal is to reduce the pain and inflammation associated with injury, to encourage the injured tissue to heal with normal structure and function, and to ultimately return the horse to the highest level of performance possible following recovery.
Ultrasound-guided hip joint injection is a joint injection in the hip, assisted by medical ultrasound. Hip and groin pain often presents a diagnostic and therapeutic challenge. The differential diagnosis is extensive, comprising intra-articular and extra-articular pathology and referred pain from lumbar spine, knee and elsewhere in the pelvis. Various ultrasound-guided techniques have been described in the hip and groin region for diagnostic and therapeutic purposes. Ultrasound has many advantages over other imaging modalities, including portability, lack of ionizing radiation and real-time visualization of soft tissues and neurovascular structures. Many studies have demonstrated the safety, accuracy and efficacy of ultrasound-guided techniques, although there is lack of standardization regarding the injectates used and long-term benefit remains uncertain.
A disease-modifying osteoarthritis drug (DMOAD) is a disease-modifying drug that would inhibit or even reverse the progression of osteoarthritis. Since the main hallmark of osteoarthritis is cartilage loss, a typical DMOAD would prevent the loss of cartilage and potentially regenerate it. Other DMOADs may attempt to help repair adjacent tissues by reducing inflammation. A successful DMOAD would be expected to show an improvement in patient pain and function with an improvement of the health of the joint tissues.
Ophthalmic viscosurgical devices (OVDs) are a class of clear gel-like material used in eye surgery to maintain the volume and shape of the anterior chamber of the eye, and protect the intraocular tissues during the procedure. They were originally called viscoelastic substances, or just viscoelastics. Their consistency allows the surgical instruments to move through them, but when there is low shear stress they do not flow, and retain their shape, preventing collapse of the anterior chamber. OVDs are available in several formulations which may be combined or used individually as best suits the procedure, and are introduced into the anterior chamber at the start of the procedure, and removed at the end. Their tendency to remain coherent helps with removal, as the cohesive variants tend to be drawn into the aspiration orifice without breaking up.
