Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2002-02-22
2003-07-29
Wilson, James O. (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C536S123100, C424S439000
Reexamination Certificate
active
06599888
ABSTRACT:
The subject of the present invention is the use of preparations based on chondroitin sulfate and chitosan for the preparation of compositions intended for the prevention or treatment of rheumatic conditions and, in particular, degenerative arthropathies, by the general route.
The joints and the various connective tissues of which they consist (cartilages, fibrocartilages, synovial membranes, ligaments and the like) are constantly subjected to mechanical stresses and to stresses which may lead to inflammatory pathologies such as arthritis or degenerative pathologies such as osteoarthritis, which are responsible for their blockage. These conditions may be acute at the level of the joints in the neck, the shoulders, the back, the hips, the forelimbs such as the elbows and the wrists, the hindlimbs such as the knees and the ankles, as well as the fingers or the toes. These pathologies are very frequent and affect both humans and animals.
Mainly two families of antiinflammatory compounds are used in human and veterinary rheumatology: the glucocorticosteroids and the NSAIDs (or nonsteroidal anti-inflammatory drugs: salycilates, indoles and related compounds, propionics, pyrazoles, anthranylines and the like). Although relieving pain and reducing the inflammatory state of connective tissues during their use, these compounds have only a pain-relieving function and do not allow a return to the normal state by the reconstitution of the tissues. Thus, these treatments are in the long term ineffective, or even harmful, because they block the natural processes for the defence of the body and lead to a destruction of the connective tissues.
When they are subjected to exercise, stress and in particular when they are the seat of lesions, the connective tissues naturally produce large quantities of collagen and of proteoglycans (PG), which are major components of these tissues, so as to become reconstituted.
These compounds, as well as their mechanisms of biosynthesis and of action, are perfectly known and described in the literature.
Collagen is manufactured from amino acids, in particular from proline, glycine and lysine, and its biosynthesis is stimulated by the presence of glucosamine.
Proteoglycans, which are large macromolecular complexes, for their part, consist of modified long chains of sugars called glycosaminoglycans (GAG) such as hyaluronic acid, chondroitin sulfates or alternatively heparin, and of which glucosamine is a precursor.
In the processes for the reconstitution of connective tissues, collagen and proteoglycans form a matrix which confers on the tissues their mechanical properties. However, the processes for the in vivo biosynthesis of collagen and of proteoglycans from precursor molecules are relatively long, which constitutes an impediment to the repair of these tissues.
Accordingly, to promote the reconstitution of the connective tissues, some treatments consist in bringing exogenous precursor molecules into the body.
Thus, it has been proposed, in U.S. Pat. No. 5,145,841, to treat rheumatic conditions of an inflammatory nature and, in particular, arthritis, by injecting, either directly into the tissues where the inflammation exists, or into the general circulation (by the intramuscular, subcutaneous or intravenous route), compositions comprising at least two compounds chosen from hyaluronic acid, corticoids and sulfated polysaccharides of the heparin sulfate and chondroitin sulfate type, the latter being preferably used in the form of complexes with a metal ion.
Moreover, U.S. Pat. No. 5,364,845 and No. 5,587,363 as well as European patent application No. 0 693 928 describe compositions intended for the protection and repair of the connective tissue, which are, for their part, intended to be administered by the oral route and which consist of combinations between an amino sugar and a glycosaminoglycan with optionally a manganese salt. The amino sugar is chosen from glucosamine, its salts and mixtures thereof, while the glycosaminoglycan is chosen from chondroitin sulfates, their salts and mixtures thereof.
Although these combinations have shown a synergistic effect compared with compositions containing either glucosamine alone, or chondroitin sulfate alone, it is known that the exogenous molecules thus provided to the body and, in particular, the chondroitin sulfates and their salts, are substantially degraded in vivo. This degradation reduces the quantity of precursor molecules capable of being used for the reconstruction of the connective tissue and, consequently, the expected therapeutic benefit, in particular in the case where these molecules are administered by the oral route.
It is therefore desirable to have compositions with enhanced therapeutic efficacy.
Chitosan is a polysaccharide which is obtained by a more or less total N-deacetylation of the chitin. The hydrolysis of chitin, the homopolymer of N-acetyl-D-glucosamine, and of chitosan leads to the formation of glucosamine, the principal precursor of the sugars involved in the synthesis of glycosaminoglycans.
Chitosan has recognized film-forming, reconstituting, antibacterial, antifungal and wound-healing properties which have led to its use in medicine, in particular as a constituent of biomaterials intended to be used in orthopedic, plastic and reconstructive surgery, either as artificial skin, or as matrix capable of allowing bone, nerve or skin cells to become regenerated. These uses are for example described in U.S. Pat. No. 5,166,187 and in international application No. WO 96/02259.
Recently, DENUZIERE et al. (
Electrophoresis
, 1997, 18, 745-750) have shown, in vitro, that chitosan protected, at a physiological pH, chondroitin sulfates from hydrolysis when these sulfates were complexed beforehand, in aqueous medium, with chitosan.
Chitosan, its salts and its derivatives are defined in greater detail in many books, in particular in the book by MUZZARELLI entitled “The Polysaccharides” (1985) Academic-Press.
However, the Inventors have observed that the combination of a chondroitin sulfate or of a salt thereof with either chitosan or a salt or a derivative thereof, or alternatively a salt of such a derivative, makes it possible, unexpectedly, to obtain compositions which exhibit a therapeutic effect/dose of chondroitin sulfate ratio markedly greater than that exhibited by the compositions provided in U.S. Pat. No. 5,364,845, U.S. Pat. No. 5,587,363 and EP-A-0 693 928.
Thus, for chondroitin sulfate doses administered which are equivalent, or even lower, compositions comprising both chondroitin sulfate (or a salt of such a sulfate) and chitosan (or a salt, a derivative or a salt of a derivative of chitosan) have been found to improve more rapidly the clinical signs than the composition provided in the abovementioned state of the art; in particular, the compositions prepared by the Inventors have shown that they made it possible to reduce more rapidly the symptoms of pain and to improve mobility more quickly, as well as the tolerance to exercise.
The present invention therefore relates to the use of a preparation comprising:
a) from 1 to 50% by weight, relative to the total weight of the preparation, of at least one compound chosen from chondroitin sulfates and their salts, and
b) from 1 to 66% by weight, relative to the total weight of the preparation, of at least one compound chosen from chitosan, its salts, its derivatives and the salts of these derivatives, for the preparation of a composition for the prevention or treatment of rheumatic conditions by the general route.
For the purposes of the present invention, the expression “general route” is understood to mean any route for administration of the composition allowing systemic distribution of the active ingredients which it contains, that is to say the enteral (oral and rectal) route, the parenteral (intramuscular, intravenous and subcutaneous) route and the transdermal route, excluding any in situ application of said composition.
According to a first preferred feature of the invention, the preparation comprises a sodium chondroitin sulfate.
Accor
Derrieu Guy
Pougnas Jean-Luc
Krishnan Ganapathy
Lowe Hauptman & Gilman & Berner LLP
Virbac
LandOfFree
Chondroitin sulphate and chitosan compositions for treating... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Chondroitin sulphate and chitosan compositions for treating..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Chondroitin sulphate and chitosan compositions for treating... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3063203