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What is Cartrophen Vet and how does it work?

Cartrophen Vet (100mg/mL of pentosan polysulfate sodium or PPS) is a treatment for osteoarthritis (OA, also known as degenerative joint disease or DJD) and related musculoskeletal disorders in dogs and horses. It provides pain relief by acting on the pathology within the joint that causes pain and lameness. Cartrophen Vet has many sites of action within the underlying processes of the arthritis disease which helps maintain joint health including preserving joint cartilage. It is therefore classified as a disease modifying osteoarthritis drug (DMOAD).

Cartrophen Vet is a prescription only, injectable, polysulfated polysaccharide of plant origin.

Cartrophen Vet will benefit acute through to chronic OA due to the progressive nature of this disease. Early intervention with Cartrophen Vet in acute injuries will maximise the restoration of normal connective tissue function.

With 20% of dogs over one year of age suffering from OA (Hegemann et al., 2002) and 60% of lameness in the horse related to OA (Caron and Genovese, 2003), Cartrophen Vet and DMOAD represent the rational approach to the medical treatment of OA.

The effective dosing and dosage regimen is discussed in 'What is the Cartrophen Vet dosage and dosing regimen?'.

 

How does Cartrophen Vet work?

Cartrophen Vet is a treatment, which has activity that works to correct the underlying metabolism of the OA. By re-balancing the metabolic processes it preserves joint health and subsequently provides relief from the clinical signs of OA. Cartrophen Vet's changes to the disease are evident in its long-term effects. Benefits are received well beyond the treatment period of 4 weeks with repeat treatments in some cases at one-year intervals. Cartrophen Vet has shown to be effective in 80% of dogs treated(Francis and Read, 1993; Cullis-Hill and Ghosjh, 1994; Bouck et al, 1995; Read et al, 1996; Smith et al 2001) , further discussed in 'How effective is Cartrophen Vet?'.

Cartrophen Vet has been shown to exhibit the following modes of action:

  1. Stimulates cartilage production - Stimulates chondrocytes to synthesize cartilage matrix (Rogachefsky et al., 1993),
  2. Improves the quantity and quality of synovial fluid – Stimulates synoviocyte biosynthesis of hyaluronan, improving both the quantity and molecular weight (Hutadilok et al., 1988 and Francis et al., 1993),
  3. Stimulates stem cell activity and cartilage cell differentiation – Promotes Mesenchymal precursor cell (MPC) proliferation and cartilage cell differentiation (Ghosh et al., 2010). Importantly, this is relevant with the frequency of MPCs elevated in arthritic cartilage (Alsalameh et al., 2004),
  4. Increased blood supply and nutrition to the joint and subchondral bone - Mobilizes thrombi and fibrin deposits, lipids and cholesterol in synovial tissues and subchondral blood vessels (Ghosh and Cheras, 2001) in order to allow increased blood flow to key areas of the synovial joint.
  5. Strong anti-inflammatory properties – The potent anti-inflammatory activities of PPS have been consistently demonstrated in different models of severe inflammation (Ghosh, 1999),
  6. Inhibits cartilage degrading enzymes – The collagenase catabolic enzyme is inhibited by the stimulation of tissue inhibitor metalloproteinase (Rogachefsky et al., 1993),
  7. Increased production of free radical scavenging enzymes - Stimulates free radical scavenging enzymes superoxide dismutase (Brown et al., 1994) and lipase (Brunaud et al., 1967),
  8. Stimulates important growth factors that promote cartilage growth - Increases the production of the essential trophic factor for cartilage, insulin-like growth factor-1 (IGF-1) (Clemmons et al., 2002), which stimulates incorporation of sulfate and encourages cartilage growth
  9. Affinity for cartilage – The strong binding of the drug to cartilage protein results in therapeutic concentrations for up to 4 days (Data on file Biopharm Australia Pty Ltd)
  10. Inhibits and modulates a range of noxious substances – such as pro-inflammatory mediators, bio-active amines such as: histamine, serotonin, superoxide free radical, enzymes such as elastase, hyaluronidase, cathepsins, THF-α converting enzyme (TACE) and proteins of the complement system which are implicated in the degradation of the cartilage matrix components (Ghosh, 1999);

These modes of action address multiple elements within the 'arthritis cycle', further discussed in 'What is the arthritis cycle?'. Note the sites of action of Cartrophen Vet in diagram below, denoted with a star.

Clinical Aids and Further Information

  1. DMOAD Brochure – The DMOAD brochure provides a scientific overview of OA and some of the studies behind the modes of action in Cartrophen Vet - Download PDF
  2. DMOAD pamphlet – This is a short form summary of the DMOAD brochure that covers much the same material as this section and the website. It is perfect for those that want to read up on the DMOAD properties and might not have the time - Download PDF
  3. Joint Poster – This is a client aid to assist with explanations to pet owners about OA and the changes in the joint and how Cartrophen Vet is going to address some of these changes - Download PDF
  • How effective is Cartrophen Vet?
  • Is Cartrophen Vet safe?

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    REFERENCES

    Alsalameh S, Amin R, Gemba T, and Lotz M (2004) Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage. Arthritis Rheum. 2004 May;50(5):1522-32)

    Bouck GR, Miller CW and Taves CL (1995). A comparison of surgical and medical treatment of fragmented coronoid process and osteochondritis dissecans of the canine elbow. V.C.O.T. 8: 177-183

    Bowman L, et al. (1994) Calcium pentosan polysulphate (CaPPS) stimulates release of superoxide dismutase (SOD) from endothelium in vitro and in vivo. Int. Soc. Free Radical Res., 7th Biennial Meeting 1994

    Brunaud M et al (1967) The clearing effect of xylane sulfate polyesters on plasma lipids. Progr Biochem Pharmacol 3:393-402

    Caron J, Genovese L. in Diagnostics and Management of Lameness in the Horse 2003;746-763.

    Clemmons DR, Busby WH, Garmong A, Schultz DR, Howell DS, Altman RD, Karr R (2002). Inhibition of insulin-like growth factor binding protein 5 proteolysis in articular cartilage and joint fluid results in enhanced concentrations of insulin-like growth factor 1 and is associated with improved osteoarthritis. Arthritis Rheum. 46(3): 694-703

    Cullis-Hill D and Ghosh P (1994). Joint Convention of L'Ordre des. Medicins veterinaries du Quebec and the Canadian Veterinary Medical Association, Quebec City, Canada, July 6-9

    Francis DJ, Hutadilok N, Kongtawelert P, Ghosh P (1993) Pentosan polysulphate and glycosaminoglycan polysulphate stimulate the synthesis of hyaluronan in vivo. Rheumatol Int 13:61-64

    Francis DJ and Read RA (1993). Pentosan polysulphate as a treatment for osteoarthritis (degenerative joint disease) in dogs. Aust. Vet. Practit. 23(2):104-109

    Ghosh P and Cheras PA (2001). Vascular mechanisms in osteoarthritis. Best Pract. Res. Clin. Rheumatol. 15(5): 693-710

    Ghosh P. (1999) The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment. Seminars in Arthritis and Rheumatism 28(4):211 267.

    Ghosh P, Wu J, Shimmon S, Zannettino A, Gronthos S, Itescu S (2010) Pentosan polysulfate promotes proliferation and chondrogenic differentiation of adult human bone marrow-derived mesenchymal precursor cells. Arthritis Research & Therapy, 12:R28

    Hegemann N, Kohn B, Brunnberg L, Schmidt MF (2002) Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders. Osteoarthritis Cart. 10, 714-721

    Hutadilok N, Ghosh P, and Brooks PM (1988) Binding of haptoglobin, inter-a-trypsin inhibitor, and a, proteinase inhibitor to synovial fluid hyaluronate and the influence of these proteins on its degradation by oxygen derived free radicals. Curr. Ther. Res. 4: 845-860;

    Klocking H-P and Markwardt F (1986). Release of plasminogen activator by pentosan polysulphate Thromb. Res. 41: 739-744

    Little C and Ghosh P.(1996) In: McIlwraith CW and Trotter GW editors. Joint Disease in the Horse. WB Saunders Company, Philadelphia, 1996: 281-292.

    Read RA, Cullis-Hill D and Jones MP (1996). Systemic use of pentosan polysulfate in the treatment of osteoarthritis. J.Small Anim Pract. 37: 108-114

    Rogachefsky RA, Dean DD, Howell DS, Altman RD (1993) Treatment of canine osteoarthritis with insulin-like growth factor-1 (IGF-1) and sodium pentosan polysulfate. Osteoarthritis Cart 1:105-114

    Smith JG, Hannon RL, Brunnberg L, Gebski V, Cullis-HiII D (2001) A Randomised double blind comparator clinical study of the efficacy of sodium pentosan Polysulfate injection and carprofen capsules in arthritic dogs, Journal of the Osteoarthritis Research Society International, 9(b):S21-S22