The cartilage of the joints is called hyaline cartilage (from the Greek "hyalos" which means glass); hyaline cartilage is found not only on all surface of bones that move (articular cartilage) but also in the nose, larynx, ribs and trachea. This cartilage consists of 70% water, about 10% collagen Type II, and the rest is various protein and specialized complex sugars, called proteoglycans. The collagen and the proteoglycans form a meshwork that confers upon this cartilage stiffness, viscoelasticity, and durability. The articular cartilage provides load bearing, resilience, a low friction surface and distributes the load over the entire synovial joint. Even though the articular cartilage is very thin (about one eighth of an inch thick) it performs its function for the life of the individual (80-90 years or more) without any significant deterioration, unless it becomes injured or diseased.
There are two major diseases that affect cartilage, namely osteoarthritis and rheumatoid arthritis; both osteoarthritis and rheumatoid arthritis result in degradation and degeneration of the articular cartilage. Osteoarthritis is a disease of cartilage only and does not have an immunological component. The major symptoms of osteoarthritis are pain, stiffness, crackling, and enlargement and deformities of the affected joints; at the early stage of osteoarthritis there is little inflammation and swelling of the joints, however in advanced stages swelling and inflammation is usually present. Rheumatoid arthritis is an autoimmune systemic disease accompanied by severe inflammation of the joints. In most patients rheumatoid arthritis begins with a general feeling of malaise, fatigue, often accompanied by diffuse musculoskeletal pain. Eventually the disease progresses resulting in pain on motion, tenderness, swelling and deformation of multiple joints; because rheumatoid arthritis is a systemic disease, it may be accompanied by extra-articular complications, such as anemia, vasculitis, scleritis, pleurisy, pericarditis, and peripheral neuritis.
The accepted modality of treatment is a regimen of nonsteroidal anti-inflammatory drugs, particularly of the aspirin type, aimed primarily to reduce pain and inflammation, maintain joint mobility, and prevent deformity. In severe cases of rheumatoid arthritis gold compounds and certain cytotoxic drugs are often used. Even though these drugs may resolve symptoms, they do not alter the course of the disease. To arrest the course of the disease, it is necessary to eliminate the cause of the disease and to rebuilt the degraded cartilage. In rheumatoid arthritis terminating the immune reaction should arrest the course of the disease; in osteoarthritis, inhibition of the enzymes that degrade the extracellular matrix, i.e., collagenase and chondroitinases, should arrest the progression of the disease. Administration of glucosamine should facilitate rebuilding the degraded cartilage.
In the last few years novel approaches to the treatment of osteoarthritis and rheumatoid arthritis have emerged. Drovanti et al, Clinical Therapeutics, 3:260-272 (1980), reported that oral glucosamine sulphate is effective in the treatment of osteoarthritis. Fassbender et al, Ostheoarthritis and Cartilage, 2:61-69 (1994), have reported that glucosamine is more effective in the treatment of osteoarthritis than ibuprofen. Pipitone, Drugs Exper. Clin. Res., 17:3-7 (1991), has reported that chondroitin sulfate protects cartilage from degradation. Trentham et al, Science, 261:1727-1730 (1993), reported that oral administration of a soluble form of collagen Type II resulted in significant improvement of rheumatoid arthritis symptoms. Barnett et al, Arthritis and Rheumatism, 39:623-628 (1996), also reported that administration of collagen Type II resulted in beneficial effects in patients suffering from Juvenile rheumatoid arthritis.
Boron appears to have some beneficial effects on some form of arthritis (Nwenham, Environ Health Perspect, 102:Suppl 7:83-85, 1994) however, its precise mechanism is not known. It is possible that boron acts by inhibiting the activated kallikrein-kinin system which appears to be operative in chronic inflammatory arthritis (Colman et al, Proc Assoc Am Physicians, 109:10-22, 1997).
Two nutritional supplements, namely chondroitin sulfate and glucosamine, have been used extensively in animals and man and have been shown to be effective in alleviating osteoarthritis (Theodosakis et al, in "The Arthritis Cure" St. Martin Press, New York, 1997). Vitamin C has been shown to be a critical agent for the normal synthesis and assembly of newly synthesized collagen. Collagen Type II has been used to treat rheumatoid arthritis in humans with some success, Barnett et al, "Treatment of Rheumatoid arthritis with oral Type II collagen", in Arthritis and Rheumatism, 41:290-297 (1998). In addition boron has been shown to be beneficial to patients suffering with osteoarthritis and to be beneficial for normal health of bone and joints (Nwenham, Environ Health Perspect., 102:Suppl 7:83-85, 1994).
U.S. Pat. No. 5,399,347 describes the use of collagen Type II or biologically active collagen peptides for the treatment of rheumatoid arthritis. U.S. Pat. No. 5,529,786 describes the use of animal tissue containing Collagen Type II for the treatment of rheumatoid arthritis. U.S. Pat. No. 5,364,845 describes the use of combined glucosamine, chondroitin sulfate and manganese for the treatment of osteoarthritis.
U.S. Pat. No. 5,529,786 has described the preparation of Type II collagen for use in treating rheumatoid arthritis, although the collagen is crudely prepared in various forms such as "diced cartilage", liquid nitrogen cartilage powder and acetic acid soluble collagen.
USPTO Backgrounds
USPTO Backgrounds