sodium hyaluronate

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.{{cite journal | vauthors = Boucher WS, Letourneau R, Huang M, Kempuraj D, Green M, Sant GR, Theoharides TC | title = Intravesical sodium hyaluronate inhibits the rat urinary mast cell mediator increase triggered by acute immobilization stress | journal = The Journal of Urology | volume = 167 | issue = 1 | pages = 380–384 | date = January 2002 | pmid = 11743360 | doi = 10.1016/S0022-5347(05)65472-9 }}

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|date=January 2017}}

Adverse effects are relatively rare when used to treat the joints.

When used in ophthalmological procedures, sodium hyaluronate may cause postoperative inflammation, corneal edema or decompensation, and short-term increases in intraocular pressure.{{citation needed|date=January 2017}}

===Intra-articular injection===

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.{{cite web|title=Hyaluronate sodium: Indications, Side Effects, Warnings|url=https://www.drugs.com/cdi/hyaluronate-sodium.html|work=Drugs.com|access-date=25 February 2014|format=Web|date=5 February 2014}}{{cite journal | vauthors = Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE | title = Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis | journal = Annals of Internal Medicine | volume = 162 | issue = 1 | pages = 46–54 | date = January 2015 | pmid = 25560713 | doi = 10.7326/M14-1231 | s2cid = 207538194 }}{{cite journal | vauthors = Mandl LA, Losina E | title = Relative efficacy of knee osteoarthritis treatments: are all placebos created equal? | journal = Annals of Internal Medicine | volume = 162 | issue = 1 | pages = 71–72 | date = January 2015 | pmid = 25560716 | pmc = 4545522 | doi = 10.7326/M14-2636 }}

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.{{cite journal | vauthors = Puhl W, Scharf P | title = Intra-articular hyaluronan treatment for osteoarthritis | journal = Annals of the Rheumatic Diseases | volume = 56 | issue = 7 | pages = 441 | date = July 1997 | pmid = 9486013 | pmc = 1752402 | doi = 10.1136/ard.56.7.441 }} It is generally used as a last resort before surgery{{cite journal | vauthors = Karlsson J, Sjögren LS, Lohmander LS | title = Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study | journal = Rheumatology | volume = 41 | issue = 11 | pages = 1240–1248 | date = November 2002 | pmid = 12421996 | doi = 10.1093/rheumatology/41.11.1240 | doi-access = free }} and provides symptomatic relief, by recovering the viscoelasticity of the articular fluid, and by stimulating new production of synovial fluid.{{cite journal | vauthors = Jubb RW, Piva S, Beinat L, Dacre J, Gishen P | title = A one-year, randomised, placebo (saline) controlled clinical trial of 500-730 kDa sodium hyaluronate (Hyalgan) on the radiological change in osteoarthritis of the knee | journal = International Journal of Clinical Practice | volume = 57 | issue = 6 | pages = 467–474 | year = 2003 | pmid = 12918884 | doi = 10.1111/j.1742-1241.2003.tb10535.x | s2cid = 28214461 }} Use of sodium hyaluronate may reduce the need for joint replacement.{{cite journal | vauthors = Kotz R, Kolarz G | title = Intra-articular hyaluronic acid: duration of effect and results of repeated treatment cycles | journal = American Journal of Orthopedics | volume = 28 | issue = 11 Suppl | pages = 5–7 | date = November 1999 | pmid = 10587245 }} 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.{{cite journal | vauthors = Bannuru RR, Natov NS, Dasi UR, Schmid CH, McAlindon TE | title = Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis | journal = Osteoarthritis and Cartilage | volume = 19 | issue = 6 | pages = 611–619 | date = June 2011 | pmid = 21443958 | doi = 10.1016/j.joca.2010.09.014 | doi-access = free | pmc = 11678314 }} It may also be effective when used with the ankle joint.{{cite journal | vauthors = Salk RS, Chang TJ, D'Costa WF, Soomekh DJ, Grogan KA | title = Sodium hyaluronate in the treatment of osteoarthritis of the ankle: a controlled, randomized, double-blind pilot study | journal = The Journal of Bone and Joint Surgery. American Volume | volume = 88 | issue = 2 | pages = 295–302 | date = February 2006 | pmid = 16452740 | doi = 10.2106/JBJS.E.00193 }}

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.{{cite journal | vauthors = Shimmura S, Ono M, Shinozaki K, Toda I, Takamura E, Mashima Y, Tsubota K | title = Sodium hyaluronate eyedrops in the treatment of dry eyes | journal = The British Journal of Ophthalmology | volume = 79 | issue = 11 | pages = 1007–1011 | date = November 1995 | pmid = 8534643 | pmc = 505317 | doi = 10.1136/bjo.79.11.1007 }} 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.[http://www.rxlist.com/healon-drug/indications-dosage.htm "Healon (Sodium Hyaluronate)"] [package insert]. (2002). Kalamazoo, Michigan: Pharmacia Corporation. (Web). RxList. (Updated 8 December 2004). RxList, Inc. Retrieved 25 February 2014.

===Skin injections in plastic surgery===

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.{{cite web |url=https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/CosmeticDevices/WrinkleFillers/ucm227749.htm |title=Soft Tissue Fillers Approved by the Center for Devices and Radiological Health |date= 2015-07-27 |publisher=U.S. Food and Drug Administration}} They are also used as a filler of lips or in other parts of the body, though not FDA approved.{{cite journal | vauthors = Beasley KL, Weiss MA, Weiss RA | title = Hyaluronic acid fillers: a comprehensive review | journal = Facial Plastic Surgery | volume = 25 | issue = 2 | pages = 86–94 | date = May 2009 | pmid = 19415575 | doi = 10.1055/s-0029-1220647 | s2cid = 12498280 }}

The filling effect is temporary and lasts for about six months or longer in most people.{{cite web |url=https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm049349.htm |title=Filling in Wrinkles Safely |date=2016-12-20|publisher=U.S. Food and Drug Administration }}

Topically applied sodium hyaluronate can facilitate the absorption of biomacromolecules, i.e. pharmaceuticals, and function like a nanocarrier.{{cite journal | vauthors = Wickens JM, Alsaab HO, Kesharwani P, Bhise K, Amin MC, Tekade RK, Gupta U, Iyer AK | display-authors = 6 | title = Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy | journal = Drug Discovery Today | volume = 22 | issue = 4 | pages = 665–680 | date = April 2017 | pmid = 28017836 | pmc = 5413407 | doi = 10.1016/j.drudis.2016.12.009 }} 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.{{cite journal | vauthors = Witting M, Boreham A, Brodwolf R, Vávrová K, Alexiev U, Friess W, Hedtrich S | title = Interactions of hyaluronic Acid with the skin and implications for the dermal delivery of biomacromolecules | journal = Molecular Pharmaceutics | volume = 12 | issue = 5 | pages = 1391–1401 | date = May 2015 | pmid = 25871518 | doi = 10.1021/mp500676e }}

Transepidermal water loss increased by 55.5% with low-molecular weight, and was reduced by 28% with crosslinked resilient, and by 16% with HMW.{{cite journal | vauthors = Sundaram H, Mackiewicz N, Burton E, Peno-Mazzarino L, Lati E, Meunier S | title = Pilot Comparative Study of the Topical Action of a Novel, Crosslinked Resilient Hyaluronic Acid on Skin Hydration and Barrier Function in a Dynamic, Three-Dimensional Human Explant Model | journal = Journal of Drugs in Dermatology | volume = 15 | issue = 4 | pages = 434–441 | date = April 2016 | pmid = 27050698 | url = http://jddonline.com/articles/dermatology/S1545961616P0434X }} Its efficacy against wrinkles has not been tested in clinical trials.{{cite news |url=https://www.latimes.com/archives/la-xpm-2009-aug-27-la-ig-beauty6-2008jul06-story.html |title=Makeup gets in on the anti-aging craze | vauthors = Stukin S |date= 27 August 2009 |newspaper=The LA Times}}

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.{{cite web | url = https://www.drugs.com/cdi/hylira-gel.html | title = Hylira gel: Indications, Side Effects, Warnings |date=14 February 2019| publisher = Drugs.com|access-date=16 March 2019 }}

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.{{cite journal | vauthors = Kuehl C, Zhang T, Kaminskas LM, Porter CJ, Davies NM, Forrest L, Berkland C | title = Hyaluronic Acid Molecular Weight Determines Lung Clearance and Biodistribution after Instillation | journal = Molecular Pharmaceutics | volume = 13 | issue = 6 | pages = 1904–1914 | date = June 2016 | pmid = 27157508 | pmc = 5200957 | doi = 10.1021/acs.molpharmaceut.6b00069 }}

===Intravesical instillation===

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.{{cite web | url = https://www.syner-med.com/product/hyacyst | title = Hyacyst® (sodium hyaluronate) | date = November 2021 | publisher = Syner-Med | access-date = 29 September 2022}} {{cite web | url = https://bladderhealthuk.org/interstitial-cystitis/icbps-treatments/intravesical-medications/cystistat | title = Cystistat® | date = 2022 | publisher = Bladder Health UK | access-date = 29 September 2022}}

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.{{cite web | url = https://www.esht.nhs.uk/wp-content/uploads/2017/06/0445.pdf | title = Bladder Instillation of Cystistat (sodium hyaluronate) | date = 5 September 2020 | publisher = East Sussex Healthcare NHS Trust | access-date = 29 September 2022}}{{cite web | url = https://www.accessdata.fda.gov/cdrh_docs/pdf18/P180040D.pdf | title = Patient Information Triluron™ (Sodium Hyaluronate) | date = 2019 | publisher = Fidia Pharma USA | access-date = 29 September 2022}}

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.{{cite book | title = History of Hyaluroan Science: From Basic Science to Clinical Applications | vauthors = Hargittai M, Hargittai I, Balazs EA | volume = 2 | publisher = Pubmatrix | date = 2011 | isbn = 978-0-9820350-4-7 }} 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.{{cite web | url = http://www.fidiapharma.us/en/news-events/2011/fidia-farmaceutici-s-p-a-to-distribute-and-promote-hyalgan-sodium-hyaluronate-for-treatment-of-osteoarthritis,3,13 | archive-url = https://web.archive.org/web/20140727193936/http://www.fidiapharma.us/en/news-events/2011/fidia-farmaceutici-s-p-a-to-distribute-and-promote-hyalgan-sodium-hyaluronate-for-treatment-of-osteoarthritis,3,13 | archive-date = 27 July 2014 | date = 26 September 2011 | url-status = dead | title = Fidia Farmaceutici S.p.A. to Distribute and Promote HYALGAN® (sodium hyaluronate) for Treatment of Osteoarthritis | publisher = Fidia Pharma }}

• [https://pubchem.ncbi.nlm.nih.gov/compound/Hyaluronic-acid-sodium-salt Hyaluronic acid sodium salt]
• [https://www.ulprospector.com/de/eu/PersonalCare/Detail/3345/225521/Hyaluronic-Acid--Sodium-Salt Biochem/physiol Actions]
• [https://hyaluronicacid.net/ Hyaluronic Acid]
• [https://www.sigmaaldrich.com/catalog/product/sigma/h5542 Legal Information]

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{{Glycosaminoglycans}}

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Category:Glycosaminoglycans

Category:Organic sodium salts