Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ketone doai
Reexamination Certificate
2000-09-14
2002-12-10
Tate, Christopher R. (Department: 1651)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ketone doai
C424S725000
Reexamination Certificate
active
06492429
ABSTRACT:
FIELD OF THE INVENTION
The invention is concerned with compositions for the treatment of osteoarthritis and related diseases and with methods for treating osteoarthritis.
BACKGROUND OF THE INVENTION
Osteoarthritis (OA) is a degenerative joint disease, which develops by wear and tear of the joints during aging. OA mostly affects the weight-bearing joints such as spine, knees and hips, but thumb and finger joints may also be affected. Repetitive mechanical injury of the cartilage eventually results in loss of cartilage and damage to joint surfaces and adjacent bone. As a result of the tissue destruction, inflammatory cells invade the joint and the synovial membrane which is manifested by pain, swelling and stiffness of the affected joints. The repetitive mechanical injury leads to pathological changes that result in loss of proteoglycans and collagen from the cartilage matrix, which in turn leads to surface erosion and decreased loading capacity, In OA, chondro-cytes show a reduced potential to synthesize matrix constituents (proteoglycans and collagen fibers) and the expression of proteolytic enzymes (called matrix metallo-proteases, MNMP's) contributes to cartilage destruction and release of proteoglycan fragments in the synovial fluid. The inflammatory responses to the mechanical insults further contribute to cartilage destruction. The inflammatory mediator interleukin I (IL-1) is considered as the principal mediator of cartilage destruction. It induces a number of changes in chondrocytes, including the concurrent generation of significant amounts of NO (nitrogen oxide) and superoxide radicals by inducible NO synthase (iNOS) and NADPH oxidase, respectively. NO reacts with superoxide to form peroxynitrite, which is largely responsible for the decrease in proteoglycan synthesis induced by IL-1. The role of superoxide was further demonstrated by the ability of superoxide dismutase to reverse the decrease in proteoglycan synthesis. The prevention of peroxynitrite formation via selective inhibition of iNOS and thus NO formation in vivo resulted in a marked decrease of MMP's. In addition, intra-articular treatment of OA patients with superoxide dismutase reduces symptoms of OA for prolonged periods. These studies demonstrate that induction of catabolic enzymes (MMP's) and cartilage destruction is mediated via the formation of NO and O
2
−
radicals by chondrocytes or inflammatory cells. While the primary cause of OA is mechanical damage, rheumatoid arthritis (RA) is mainly the result of an autoimmune response that leads to chronic inflammation in the joint. Contrary to OA, typical manifestations of RA are an increase of parameters that are associated with inflammation, such as haematocrite and white blood cell count and pannus formation or hyperplasia of the joint capsule that leads to deformed joints. This in turn leads to morning stiffness. Although the (primary) aetiology of RA and OA are different, the pathological processes at a later stage result in some manifestations that are similar such as joint pain, cartilage degradation and general joint disability.
Lafeber et al. (
Rheumatology,
1999 (38) 1088-1093) describe in vitro studies on the utility of apocynin (4-hydroxy-3-methoxy-acetophenone, acetovanillone) for the treatment of rheumatoid arthritis.
WO 95/22323 describes the use of analogues of apocynin, in particular the 4-hydroxyethoxy analogue, for controlling free radical generation by inflammatory cells in e.g. inflammatory bowel disease, rheumatoid arthritis and several other inflammatory conditions.
U.S. Pat. No. 5,629,351 discloses a fraction of boswellic acids isolated form
Boswellia serrata
, including a hitherto unknown 2-hydroxyboswellic acid, having anti-inflammatory, anti-arthritic and anti-ulcerogenic activities. WO 97/07796 claims the use of boswellic acid for the treatment of diseases, such as lung emphysema, cystic fibrosis, rheumatoid arthritis etc, which are induced by leucocytic elastase or plasmin activity.
U.S. Pat. No. 5,401,777 relates to the use of curcumin for treating conditions associated with formation of leucotrienes from arachidonic acid, such as inflammatory bowel diseases, chronic hepatitis, bronchial asthma and psoriasis.
U.S. Pat. No. 5,494,668 describes a product to be used for the treatment of OA and other musculoskeletal diseases, containing combined extracts from
Withania somnifera
(Ashwaganda) roots,
Boswellia serrata
(Sallai guggul) gum exudate (boswellic acids),
Curcuma longa
(turmeric) rhizomes (curcumin) and
Zingiber officinale
(ginger).
SUMMARY OF THE INVENTION
It was found that osteoarthritis can be effectively treated by administration of a suitable amount of apocynin or its functional and structural analogues, preferably in the form of an extract from a Picrorhiza plant, and preferably together with further components enhancing the beneficial effect of the apocynin. Thus, the invention in a first aspect provides compositions for the treatment of osteoarthritis, containing an effective amount of apocynin or its analogues.
In a second aspect, the invention provides methods for treating osteoarthritis comprising administering to a person in need of said treatment an effective amount of apocynin or its analogues. In a third aspect, the invention provides compositions comprising apocynin or analogues and methods for the treatment of arthritis in general as caused by wear-and-tear processes, due to labour, ageing or obesity, for the treatment of developed arthritis and for the-treatment of the first symptoms of joint disorders in patients not having a familial history of rheumatism.
In a fourth aspect the invention provides compositions that are characterized by the simultaneous presence of apocynin or analogues and other components, in particular an inhibitor of inducible nitric oxide synthase and methods for treatment of arthritis in general caused by wear-and-tear, autoimmune responses in the joints, goute, or other causes of cartilage degradation.
DETAILED DESCRIPTION OF THE INVENTION
According to the invention apocynin is a highly useful component for treating osteoarthritis and related conditions. In particular, apocynin was found to be effective in retarding progression of osteoarthritis. It was found furthermore, that the inflammatory processes in arthritis can be controlled and the accompanying symptoms of stiffness and pain can be alleviated by combined administration of an inhibitor of NADPH oxidase, such as apocynin, and an inhibitor of inducible nitric oxide synthase (iNOS), such as curcumin.
Consequently, the composition of the invention contains at least 50 &mgr;g, preferably at least 100 &mgr;g, up to 1000 mg of apocynin on the basis of daily intake. The preferred daily intake is between 1 and 100 mg. Apocynin (acetovanillone) is a known compound (4-hydroxy-3-methoxy-acetophenone); most preferred is a dosage of at least 15 mg/day. According to the invention, analogues of apocynin may be used instead of or in addition to apocynin. Such analogues are in particular those in which the 4-hydroxyl group is etherified, especially with a hydroxylated alkyl group, such as 2-hydroxyethyl, 2,3-dihydroxypropyl or a sugar moiety. The latter analogue in which the sugar moiety is &bgr;-D-glucose, is commonly known as androsin. This is the usual form in which apocynin is present in fresh plants.
Preferably apocynin and/or its analogues are present in an extract obtained from apocynin- or androsin-containing plant or plant parts, such as Picrorhiza species, for example
P. kurrooa
and
P. scrophulariiflora
; the latter is also known as
Neopicrorhiza scrophulariiflora
. Cucurbitacins are known to be present in both Picrorhiza species (Stuppner et al., 1991, Wang et al., 1993). As some cucurbitacins are reported to induce immune responses and might potentially lead to adverse health effects, a prepartion is preferably chosen in which cucurbitacins are largely absent, i.e. in which the cucurbitacin level is lower than 40%, preferably lower than 20%, especially lower than 10% of the level of apocynin or
Graus Ivo Maria Franciscus
Smit Hobbe Friso
Browdy and Neimark , P.L.L.C.
N.V. Nutricia
Patten Patricia A
Tate Christopher R.
LandOfFree
Composition for the treatment of osteoarthritis does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Composition for the treatment of osteoarthritis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Composition for the treatment of osteoarthritis will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2974863