Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Reexamination Certificate
2001-07-11
2003-10-28
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
Reexamination Certificate
active
06638920
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to compositions and methods for preventing or reducing the risk or incidence of skeletal injuries in horses. The present invention further relates to compositions and methods for alleviating pain associated with skeletal injuries in horses and to treating skeletal injuries in horses. The present invention also relates to compositions and methods for treating or preventing glucocorticoid-induced bone loss in horses.
BACKGROUND OF THE INVENTION
The horse industry in the U.S. produces goods and services valued at $25.3 billion in 1996 (American Horse Council, Washington, D.C.).
Skeletal injuries are a significant cause of death in performance horses, which are horses involved in activities such as racing, pacing, and other competitive events. The loss of a performance horse to such an injury can have a profound and far reaching effect. These injuries are not only distressing to the horse owners who often have a large emotional and financial commitment at stake, and also to spectators and other horse lovers. Furthermore, these injuries can also be extremely dangerous and even life threatening for jockeys, racers, and others.
In California alone, between 150 and 200 horses die or are euthanized each year as a result of catastrophic bone injury due to racing or training. See Estberg, et al., Preventative Vet. Med. 33: 159-170, 1998, which is incorporated by reference herein in its entirety. In addition to ethical and humane considerations, there is a very strong financial incentive to properly care for and prevent and reduce the risk or incidence of skeletal injuries in horses.
The performance horse, such as a racehorse, is an athlete capable of reaching and sustaining high training and racing speeds. Under these conditions, great demands are placed on the weight-bearing structures of the musculoskeletal system. Injuries can often occur abruptly during exercise. Injuries can also be caused by chronic skeletal damage incurred while training and performing or by skeletal atrophy due to nonexercise and forced stall rest. Skeletal atrophy and bone loss is characterized by conditions such as osteoporosis or osteopenia. These conditions are characterized by a decrease in bone mass density and by microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. These undesired skeletal changes can occur relatively rapidly after only a few weeks of inactivity and raises concerns about the common practice of stall rest such as the housing of yearling horses in stalls prior to yearling sales or prior to the commencement of training. Furthermore, the necessity of submitting injured or sick horses to forced stall rest raises concerns about how best to return such horses to activity without causing injury.
Normal bone physiology involves a process wherein bone tissue is continuously being turned over by the processes of modeling and remodeling. In other words, there is normally an appropriate balance between resorption of existing bone tissue and the formation of new bone tissue. The exact mechanism underlying the coupling between bone resorption and formation is still unknown. However, an imbalance in these processes is manifested in various disease states and conditions of the skeleton.
Two different types of cells called osteoblasts and osteoclasts are involved in the bone formation and resorption processes, respectively. See H. Fleisch,
Bisphosphonates In Bone Disease, From The Laboratory To The Patient,
4th Edition, Parthenon Publishing (2000), which is incorporated by reference herein in its entirety.
Studies from the California Racetrack necroscopy studies indicate that fatal catastrophic musculoskeletal injuries in horses, principally fractures of proximal seamoid, third metacarpus and humerus, occur at an incidence of 1.7 per 1000 starts. See Estberg, L. et al., “Fatal musculoskeletal injuries incurred during racing and training in thoroughbreds”,
Journal of the American Veterinary Medical Association,
208(1): 92-96 (Jan. 1, 1996), which is incorporated by reference herein in its entirety. This is in general agreement with data from other studies (New York 1.1 per 1000 starts; Minnesota and Illinois-1.8; Japan-3.2; Kentucky-1.4, South Africa 1.4; Australia 0.3) cited by Mundy, Proc. Annual Conference of American Association of Equine Practioners, 204-220 (1997), which is also incorporated by reference herein in its entirety. The incidence of non-fatal injuries, horses which develop an abnormal gait or which require the ambulance to attend to a horse occur at rates 3-7 times higher than these catastrophic injuries.
Horses returning to racing following a lay-up (spelling) period, greater than 60 days without a race or fast time work, are 70 times more likely to suffer a fatal humeral fracture. Sixty-five percent of these incidents occur within 10 days of a lay-up. It is speculated that the spelling period predisposes the horses to disuse osteoporotic change to these long bones Carrier et al. 1998.
Buckingham, S. H. W. et al., “Osteopenic effects of forelimb immobilization in horses”,
Veterinary Record,
128: 370-373 (1991), which is incorporated by reference herein in its entirety, demonstrated that immobilization of a forelimb of horses by applying a cast for 8 weeks caused loss of bone strength and mineral content from both limbs but was more pronounced in the leg with the cast.
The following references, which are all incorporated by reference herein in their entirety, provide additional background on the subject of skeletal injuries of horses:
Porr, C. A. et al., “Deconditioning Reduces Mineral Content of the Third Metacarpal Bone in Horses”,
Journal of Animal Science,
76: 1875-1879 (1998).
Johnson, B. J. et al., “Causes of death in racehorses over a 2 year period”,
Equine Veterinary Journal,
26(4): 327-330 (1994).
Estberg, L. et al., “Relationship between race start characteristics and risk of catastrophic injury in thoroughbreds: 78 cases (1992)”,
Journal of the American Veterinary Medical Association,
212(4): 544-549 (Feb. 15, 1998).
Hoekstra, K. E. et al., “Stalling Young Horses Alters Normal Bone Growth”,
Association for Equine Sports Medicine Proceedings
, AGM, Leesburg, Va. (1998).
Carrier, T. K. et al., “Association between long periods without high-speed workouts and risk of complete humeral or pelvic fracture in thoroughbred racehorses; 54 cases (1991-1994)”,
Journal of the American Veterinary Medical Association,
212(10): 1582-1587 (May 15, 1998).
Estberg, L. et al., “High-speed exercise history and catastrophic racing fracture in thoroughbreds”,
American Journal of Veterinary Research,
57(11):1549-1555 (Nov. 1996).
Lepage, O. M. et al., “L'emploi d'un bisphosphonate (APD) dans la prevention des exoxtoses chez le poney Shetland. Eutde preliminaire.
Ann Med. Vet.,
132:391-399 (1988).
Lepage, O. M. et al., “Aspects microradiographiques et en microscopie de fluorescence d'une exotose experimentale du metacarpein chez le poney Shetland et de son traitement par un bisphosphonate, L”AhpfBP (APD). Applications possible aucheval d'arme”,
Annales Medicinae Militaris Belgicase
3(2):38-44 (1989).
Estberg, L. et al., “A cross over study of intensive racing and training schedules and risk of catastrophic musculoskeletal injury and lay-up in California thoroughbred racehorses”,
Preventative Vet. Med.,
33: 159-170 (1998).
The skeletal injuries and underlying predisposing conditions are to be distinguished from navicular disease in horses. The navicular bone is a boat-shaped bone located at the medial side of the tarsus. Navicular disease is a specific disorder of this bone, causing lameness and frequently leading to loss of function in a performance horse. Without being limited by theory, the pathophysiology of this disease is not well defined but it is thought to be related to blood circulation through the foot and particularly to the navicular bone. Disruption to this blood supply leads to physical changes in the bone, causing pain. N
Criares Theodore J.
Daniel Mark R.
Merck & Co. , Inc.
Wallinger Nicole M.
LandOfFree
Compositions and methods of preventing or reducing the risk... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions and methods of preventing or reducing the risk..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions and methods of preventing or reducing the risk... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3155690