Joints? Polysulfated Glycosaminoglycan (PSGAG)

Originally Posted by http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/191607.htm

Polysulfated Glycosaminoglycan (PSGAG):
PSGAG is a semisynthetic glycosaminoglycan prepared from bovine tracheal cartilage and composed of a polymeric chain of repeating disaccharide units. The primary glycosaminoglycan in PSGAG is chondroitin sulfate. PSGAG is approved for IM use in dogs and intra-articular and IM use in horses for the control of signs associated with noninfectious degenerative or traumatic arthritis. In horses, the recommended dosage is 500 mg, IM, every 4 days for 28 days, or 250 mg by intra-articular injection once weekly for 5 wk. In dogs, the recommended dosage is 2 mg/lb, IM, twice weekly for up to 4 wk. Following IM injection, PSGAG is absorbed into the systemic circulation and eventually incorporated into both normal and damaged cartilage. The exact mechanism of action is unknown, but in vitro studies show that PSGAG inhibits PGE2 and catabolic enzymes such as stromelysin, elastase, the metalloproteases, and others. PSGAG also increases the synthesis of hyaluronic acid, proteoglycan, and collagen in vitro. Toxicity associated with the administration of PSGAG has been minimal. Because PSGAG is chemically similar to heparin, overdosage may inhibit coagulation, and concurrent use of aspirin may prolong bleeding times. The use of PSGAG is contraindicated in septic joints.

Thoughts?

Adequan ® Canine (POLYSULFATED GLYCOSAMINOGLYCAN)
FAST ACCESS TO THE JOINTS: Beneficial levels of Adequan are already at work in all major joints within two hours after intramuscular injection, with even greater uptake (up to 73% higher) in joint tissues that are inflamed or diseased. LONG-TERM EFFECTS: Adequan Canine relieves the pain and disability of joint damage, and the relief has been shown to last up to 6 months or longer. BREAKS THE DESTRUCTIVE CYCLE: Adequan binds to damaged cartilage and boosts cartilage metabolism, facilitating repair processes. At the same time, it blocks the action of destructive enzymes that promote joint inflammation, break down the synovial fluid, and attack the cartilage. RENEWS THE JOINT FLUID: Adequan stimulates the synovial membrane to manufacture new synovial fluid to replace the thin, degraded fluid of joint disease. By doing so, Adequan helps lubricate, nourish, and clean the cartilage.

Administration: An initial 8-dose series is recommended: 2 mg/lb intramuscularly twice a week for four weeks. Adequan Canine is packaged in 5 mL (100 mg/mL) multidose vials.




Adequan Information
Description: The active ingredient in Adequan® Canine is polysulfated glycosaminoglycan (PSGAG). Polysulfated glycosaminoglycan is a semi-synthetic glycosaminoglycan prepared by extracting glycosaminoglycans (GAGs) from bovine tracheal cartilage. GAGs are polysaccharides composed of repeating disaccharide units. The GAG present in PSGAG is principally chondroitin sulfate containing 3 to 4 sulfate esters per disaccharide unit. The molecular weight for PSGAG used in the manufacture of Adequan® is 3,000 to 15,000 daltons. Each mL of Adequan® Canine contains 100 mg of PSGAG, 0.9% v/v benzyl alcohol as a preservative, and water for injection q.s. to 1 mL. Sodium hydroxide and/or hydrochloric acid added when necessary to adjust pH.

Pharmacology: The specific mechanism of action of Adequan® in canine joints is not known. PSGAG is characterized as a "disease modifying osteoarthritis drug." Experiments conducted in vitro have shown PSGAG to inhibit certain catabolic enzymes which have increased activity in inflamed joints, and to enhance the activity of some anabolic enzymes. For example, PSGAG has been shown to significantly inhibit serine proteinases. Serine proteinases have been demonstrated to play a role in the Interleukin-1 mediated degradation of cartilage proteoglycans and collagen. PSGAG is reported to be an inhibitor of Prostaglandin E2 (PGE2) synthesis. PGE2 has been shown to increase the loss of proteoglycan from cartilage. PSGAG has been reported to inhibit some catabolic enzymes such as elastase, stromelysin, metalloproteases, cathepsin B1, and hyaluronidases, which degrade collagen, proteoglycans, and hyaluronic acid in degenerative joint disease. Anabolic effects studied include ability to stimulate the synthesis of protein, collagen, proteoglycans, and hyaluronic acid in various cells and tissues in vitro. Cultured human and rabbit chondrocytes have shown increased synthesis of proteoglycan and hyaluronic acid in the presence of PSGAG. PSGAGs have shown a specific potentiating effect on hyaluronic acid synthesis by synovial membrane cells in vitro.

Absorption, distribution, metabolism, and excretion of PSGAG following intramuscular injection have been studied in several species, including rats, rabbits, humans, horses and dogs.

Studies in rabbits showed maximum blood concentrations of PSGAG following IM injection were reached between 20 to 40 minutes following injection, and that the drug was distributed to all tissues studied, including articular cartilage, synovial fluid, adrenals, thyroid, peritoneal fluid, lungs, eyes, spinal cord, kidneys, brain, liver, spleen, bone marrow, skin, and heart.

Following intramuscular injection of PSGAG in humans, the drug was found to be bound to serum proteins. PSGAG binds to both albumin and chi- and beta-globulins and the extent of the binding is suggested to be 30 to 40%. Therefore, the drug may be present in both bound and free form in the bloodstream. Because of its relatively low molecular weight, the synovial membrane is not a significant barrier to distribution of PSGAG from the bloodstream to the synovial fluid. Distribution from the synovial fluid to the cartilage takes place by diffusion. In the articular cartilage the drug is deposited into the cartilage matrix.

Serum and synovial fluid distribution curves of PSGAG have been studied in dogs and appear similar to those found in humans and rabbits.

In rabbits, metabolism of PSGAG is reported to take place in the liver, spleen, and bone marrow. Metabolism may also occur in the kidneys. PSGAG administered intramuscularly and not protein bound or bound to other tissues is excreted primarily via the kidneys, with a small proportion excreted in the feces.

Efficacy: Efficacy of Adequan® Canine was demonstrated in two studies. A laboratory study using radiolabeled PSGAG established distribution of PSGAG into canine serum and synovial fluid following a single intramuscular injection of 2 mg/lb. A clinical field trial was conducted in dogs diagnosed with radiographically-confirmed traumatic and/or degenerative joint disease of 1 or 2 joints. Joints evaluated included hips, stifles, shoulders, hocks and elbows. Fifty-one dogs were randomly assigned to receive either Adequan® Canine at 2 mg/lb of body weight or 0.9% saline. Both treatments were administered by intramuscular injection twice weekly for 4 weeks (8 injections total). Investigators administering treatment and evaluating the dogs were unaware of the treatment assignment. A total of 71 limbs in 51 dogs were evaluated. Of these, 35 limbs in 24 dogs were in the Adequan® Canine treated group. Each lame limb was scored for lameness at a walk, lameness at a trot, pain, range of motion, and functional disability. The scores for the individual parameters were combined to determine a total orthopedic score. At the end of the treatment period, dogs treated with Adequan® Canine showed a statistically significant improvement in range of motion and total orthopedic score over placebo treated control dogs.

Indications and Usage: Adequan® Canine is recommended for intramuscular injection for the control of signs associated with non-infectious degenerative and/or traumatic arthritis of canine synovial joints.

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It is an injectable joint support supplement for dogs... and although it was tested on humans (as noted in the study), it does not appear that it was approved by the FDA or released for human use.

1. If that is the case then it would be illegal to administer this product to a human.
2. The canine product may not be human grade; but since it is made by Merck you probably do not have to worry as much about quality.
3. Are your joint problems that bad? There are plenty of options out there for treatment and I would not look at something this extreme unless you have exhausted all other possibilities.

With that said, some products like Microlactin have been used quite a bit in Veterinary applications - so it is pretty resourceful of you to look at other areas in hopes of discovering potentially useful supplements.

My thoughts are that it would not be worth it to break the law for an injectable canine joint support supplement.

good thoughts. Nah my joints are alright. My shoulder joints will 'pop' once in a while after a heavy shoulder workout but its pain free (like the sound of your knuckles cracking if you have that bad habit). I figured this is because there's not enough synovial fluid. Somebody recommended real low dose deca if/when I ever run a cycle again cause apparently that adds fluid to joints, but that has its own problems (and similar legal problems). Apparently some guys are running real low dose deca year around on top of their TRT dose (but thats nearly a lifetime commitment ).

I'm just curious about what people think here and whether anybody used or thought about it. Also just wanted to bring it to people's attentions (since it sounded REAL good).

You're right it is vet-grade. I believe there is a human pharm-grade available though - it goes by a different name (I bet its more rare/harder to get).

This drug is also regularly used on Horses too (there is two equine versions, one with just PSGAG and one with PSGAG and cortisone).