Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1998-05-15
2000-05-02
Levy, Neil S.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514108, 514112, 424442, A61K 3166
Patent
active
060573066
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a method of treating the navicular disease in horses, which comprises treating the navicular disease in horses with an effective amount of at least one compound of formula ##STR2## wherein R.sub.1 is hydrogen, hydroxy, amino or halogen, and O, or of a C.sub.1 -C.sub.4 -tetraalkyl ester thereof, each in the free form, in the form of the salt and/or in the hydrate form; to a compound of formula I for use in a method of treating the navicular disease, to a composition for use in a method of treating the navicular disease, which comprises one or more than one compound of formula I, as well as to the use of a compound of formula I for the preparation of a veterinary composition for treating the navicular disease.
The navicular disease is a common cause of lameness in horses. The disease has to be treated by elaborate methods but nevertheless almost always results in the loss of the affected, but otherwise healthy, horse. The disease strikes all horse races and usually occurs in 6-12-year-old horses. The disease starts insidiously but can be detected without exception already at a stage in which the horse does not show any symptoms yet.
The pathophysiology of the navicular disease is not at all clear. Among the numerous theories regarding its etiology, two are of preeminent interest: Bad blood circulation in the foot is blamed on the one hand and changes in the biomechanical properties of the foot, i.e. the navicular bone, of the horses are blamed on the other hand. Correspondingly, there are primarily two methods of treatment which are often employed: The biomechanical explanation of the disease calls for corresponding measures of the farrier as well as for chirurgical methods. The blood circulation theory, on the other hand, rather indicates drug treatment of the horse which aims at improving the blood circulation in the navicular bone but also in the surrounding tissue. Attempts have therefore been made to achieve an improvement using anticoagulants. e.g. warfarin. The inflammation of the affected bone is also treated with steroidal and nonsteroidal antiinflammatory drugs. However, these methods are only partly successful, their efficiency is difficult to assess, they are elaborate and, in particular, they do not achieve a permanent cure of the disease. Accordingly, there is still an urgent need to solve the problem.
Surprisingly, it has now been found that the disease can be treated efficiently and with lasting effect with bisphosphonates of the above formula (I). It is known that bisphosphonates of the type of this invention have no, or only very little, influence on the blood flow and have only extremely limited antiinflammatory properties. It therefore has to be considered as particularly surprising that of all compounds these are capable of solving the problem so substantially. It has also been found that the bisphosphonates of the above formula (I) have a pronounced effect on the bone cyst like lesions that occur under the pathophysiology of navicular bone disease. They very effectively remodel the wounded bone. A particularly important advantage of the compounds of formula I is their relatively long duration of efficacy. Because the navicular disease in horses is a problem which has been known for a long time and which can cause the animal owner great losses, intense searches for solutions have already been conducted and the novel treatment of the disease with bisphosphonates of formula I is therefore particularly remarkable.
Within the scope of this invention a preferred method of treating the navicular disease in horses is that which comprises using one or more than one compound of formula (I), wherein either Ar--S--A--N(R.sub.3)--, Het--S--A--N(R.sub.3)-- or --C(.dbd.S)NHC.sub.6 H.sub.5 group, diaza- or thiazaaryl, which is bound through a ring-carbon atom or a ring-nitrogen atom, diaza- or thiazaaryl, which is bound through a ring-carbon atom or a ring-nitrogen atom, -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, Ar--C.sub.1 -C.sub.6 alkyl, Ar--O--C.sub.1 -C.sub.6 alk
REFERENCES:
patent: 3962432 (1976-06-01), Schmidt-Dunker
patent: 4086334 (1978-04-01), Schmidt-Dunker et al.
patent: 4687767 (1987-08-01), Bosies et al.
patent: 4746654 (1988-05-01), Breliere et al.
patent: 4784993 (1988-11-01), Boises et al.
patent: 4876248 (1989-10-01), Breliere et al.
patent: 4927814 (1990-05-01), Gall et al.
patent: 4939130 (1990-07-01), Jaeggi et al.
patent: 5057505 (1991-10-01), Widler et al.
patent: 5376647 (1994-12-01), Sohda et al.
patent: 5512552 (1996-04-01), Sohda et al.
Colles C. (1982) "Navicular disease and its treatment" In Practice, 3:29-36.
Devous MD, et al. (1984) "Techniques and applications of nuclear medicine in the diagnosis of equine lameness" JAVNA 184(3):318-325.
Fleisch H. (1991) "Bisphosphonates, Pharmacology and Use in the Treatment of Tumour-Induced Hypercalcaemic and Metastic Bone Disease" Drugs, v42(6):919-944.
Humpel P, et al. (1991) ZK 90 695: "A new antiarthritic drug and tissue targeting properties" Agents and Actions v32 (1/2):22-23.
Leach, D-H. (1993) "Treatment and pathogenesis of navicular disease (`syndrome`)" Equine Vet J, 25(6):477-481.
Lepage OM, et al. (1988) "L'emploi d'un bisphosphonate (ADP) dans la prevention des exostoses chex le poney Shetland. Etude prelimimaire" Ann Me d Vet, 132:391-399.
MacGregor CM (1989) Editorials, "Navicular disease--in search of definition" Equine Vet J, v21(6):389-391.
Ostblom L, et al. (1989) "Navicular bone disease: a comparative histomorphometric study" Equine Vewt J, V21(6):431-433.
Ostblom L, et al. (1982) "Histological study of navicular bone disease" Equine Vet J, v14(3):199-202.
Patel S, et al. (1993) "Drugs Used in the Treatment of Metabolic Bone Disease: Clinical Pharmacology and Therapeutic Use" Drugs, 46(4):594-617.
Pollitt C. (1990) "Navicular Disease" Veter, Continuing Education. 5:99-114.
Trotter GW. (1991) "Therapy for Navicular Disease" The Compendium on Continuing Education for Practicing Veter, v13(9):1462-1466.
Turner TA. (1986) "Shoeing principles for the management of navicular disease in horses" JAVMA, v189(3):298-301.
Turner TA. (1989) "Diagnosis and Treatment of the Navicular Syndrome in Horses" Veterinary Clinics of North America: Equine Practice, v5(1): 131-144.
Van Beek E, et al. (1994) "Structural Requirements for Bishosphonate Actions In Vitro" J of Bone and Mineral Research, v9(12): 1875-1882.
Van Gelder JM, et al. (1995) "Anticalcification and Antiresorption Effects of Bisacyphosphonates" Bone, v16(5):511-520.
Wright IM, et al. (1993) "Biomechanical considerations in the treatment of navicular disease" The Veterinary Record, 133:109-114.
Goodship Allen Edward
Green Jonathan
Wilson Alan Martin
Levy Neil S.
Morris Michael P.
Novartis Corporation
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