Heparinoid

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Heparinoid
Clinical data
Routes of
administration
Topical
Chemical data
Formula C16H19N3O5S
Molar mass 365.40 g·mol−1
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Heparinoids are glycosaminoglycans which are derivatives of heparin.[1] They include oligosaccharides and sulfated polysaccharides of plant, animal, or synthetic origin.[2] One study conducted on heparinoids.[3]

Heparinoids, like heparin, act by interacting with heparin binding proteins, generally through ionic interactions or hydrogen bonding. Some examples of heparin binding proteins include antithrombin III. It is thought that much protein interaction with heparin is not direct, and instead heparin binding protein actually interact with glycosaminoglycan (GAG) side chains or mucins bound to the heparin polymer, so it is possible that heparinoids interact with these proteins in a similar way, acquiring GAG side chains in vivo. One counter example is the protein chymase, which directly binds to heparin.[2]

Sulfonated Polysaccharides[edit]

From Animal Tissues[edit]

Dermatan sulfate is one example of a compound that is classified as a heparinoid. It is a naturally-occurring polysaccharide of O-sulfonated N-Acetyl-D-galatosamine, L-induronic acid, and D-glucuronic acid that has been clinically used as an antithrombic agent.[2]

Chondroitin sulfate shows slightly less biological activity than dermatan sulfate, and is composed of O-sulfonated N-Acetyl-D-galatosamine and D-glucuronic acid. It is theorized that this change in efficacy is related to the absence of L-induronic acid, which affects the flexibility of the polymer chain.[2]

Acharan sulfate is a heparinoid that is naturally produced by the giant African land snail, Achatina fulica. Keratan sulfate is a heparinoid that is a component of cartilage. It is found in the cornea.[2]

Chitin, a component of insect shells and fungal structures, can be de-N-acetylated to form chitosan, which when sulfonated has a significant chemical similarity to heparin. In fact, it inhibits thrombin by affecting ATIII.

Lepirudin is a recombinant preparation of the polypeptide anticoagulant secreted by leeches and is used in patients with heparin induced thrombocytopenia.

From Plant Sources[edit]

Fucoidin is a polymer composed of sulfated L-fucose.

Carrageenans are isolated from algae.

Hyaluronan functions as a heparinoid when it is sulfonated. Intra-articular injections of hyaluronic acid are used to mitigate pain and treat symptoms of osteoarthritis in the knee, but such injections are correlated with increased risk of serious side effects.[4]

Alginic acid functions as a heparinoid when it is sulfonated.

Pentosan from the bark of Fagus sylvantica, when sulfonated, acts with 1/10th of the efficacy of heparin.

From Microbial Sources[edit]

K5 polysaccharide from E. coli acts as a heparinoid when it is sulfonated.

Small Sulfonated Oligosaccharides[edit]

History[edit]

Heparin was first isolated from dog liver by medical student Jay McClean in 1916. Jorpes discovered the structure of the heparin polysaccharide in 1935, identifying that it is a highly sulfonated polymer of glycosaminoglycoglycan (GAG) and uronic acid. Around that time, heparin began to be used in the prophylaxis and treatment of post-operative thrombosis.[5]

Production[edit]

There is no industrial process for the complete synthesis of heparin; Heparin is isolated from animal tissue - generally bovine lung, porcine, and intestinal mucosa.[5] Heparinoids generally are also naturally-occurring polysaccharides, and similarly need to be purified from the plant or animal tissue that produces them.

Regulation[edit]

There is no internationally accepted molecular standard for the composition of heparin, as it is a complex polymer of GAG units and uronic acids (including D-glucuronic acid, L-iduronic acid, and D-glucosamine). Position of N-acetyl, N-sulfate, and O-sulfate groups in these uronic acids can vary, as can the branching patterns of the chain. This generates an extraordinary amount of variability between molecules of heparin.[5] Current USP standards for heparin limit levels of contamination with dermatan, chondroitin, and over-sulfonated chondroitin sulfate, as well as galactosamine levels in the sample, as determined by HPLC, H-NMR, and Strong Anion Exchange Chromatography.[6][7]

See also[edit]

References[edit]

  1. ^ Heparinoids at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. ^ a b c d e Gunay NS, Linhardt RJ (1999). "Heparinoids: structure, biological activities and therapeutic applications". Planta Medica. 65 (4): 301–6. doi:10.1055/s-1999-13990. PMID 10364832. 
  3. ^ Mehta PP, Sagar S, Kakkar VV (1975). "Treatment of superficial thrombophlebitis: a randomized, bouble-blind trial of heparinoid cream". British Medical Journal. 3 (5984): 614–6. doi:10.1136/bmj.3.5984.614. JSTOR 20406780. PMC 1674425free to read. PMID 51664. 
  4. ^ Rutjes AW, Jüni P, da Costa BR, Trelle S, Nüesch E, Reichenbach S (2012). "Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis". Ann. Intern. Med. 157 (3): 180–91. doi:10.7326/0003-4819-157-3-201208070-00473. PMID 22868835.
  5. ^ a b c Template:Nieforth, Karl A., and Zbigniew J. Witczak. 1997. "Heparin Oligosaccharides: New Analogues Development and Applications." Carbohydrates in Drug Design. New York: M. Dekker, 1997. eBook Collection (EBSCOhost), EBSCOhost (accessed November 30, 2015).
  6. ^ {{U.S. Pharmacopeia Heparin Stage Two Monograph Revisions Open Microphone Web Meeting March 3, 2009 Powerpoint Presentation. Morris, Tina S.; Szajeck, Anita; Wahab, Samir; Ambrose, Michael; Jameison, Fabian A.; <http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/key-issues/2009-03-09-HeparinMeeting.pdf> }}
  7. ^ USP Safety Data Sheet: Heparin Sodium with Oversulfated Chondroitin Sulfate. http://static.usp.org/pdf/EN/referenceStandards/msds/1304050.pdf Accessed on 11/30/2015.

External links[edit]