Methods for evaluating efficacy of anti-inflammatory on drugs on joint inflammation
First Claim
1. A joint preparation free of the host animal, comprising:
- (a) an isolated joint;
(b) a perfusate for perfusing said isolated joint;
(c) an oxygenator in fluid communication with the perfusate for oxygenating the perfusate;
(d) an inflow conduit having a first end and a second end, the first end in communication with said isolated joint for introducing said perfusate into said isolated joint;
(e) an outflow conduit having a first end and a second end, the first end in fluid communication with the isolated joint for receiving perfusate from the joint, the second end in fluid communication with the second end of the inflow conduit; and
(f) a pump in communication with the inflow conduit or outflow conduit for pumping the perfusate through said isolated joint.
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Accused Products
Abstract
The present invention provides methods for: detecting and quantifying the release of chemical agents, such as anti-inflammatory drugs from the synovial cavity of a joint into the vascular system of the joint; directly measuring the effect of chemical agents on oxygen consumption and the oxygen extraction rate of the joint cells alone; directly and simultaneously measuring the effect of anti-inflammatory drugs on hemodynamic parameters of the joint, and on transsynovial parameters of the joint, such as the permeability of the synovial membrane of a joint, the production of synovial fluid by the joint, and the composition of the synovial fluid of the joint. Each of these methods is useful for evaluating the efficacy of chemical agents on joint inflammation. The methods of the present invention employ a joint preparation which comprises: an isolated joint; a perfusate for perfusating the joint; an inflow conduit for introducing perfusate into the isolated joint; an outflow conduit for receiving perfusate from the isolated joint; means for circulating perfusate through the isolated joint; and oxygenator for oxygenating the perfusate. To quantify the release of a chemical agent, from the synovial cavity of the joint into the vascular system, the chemical agent is injected into the synovial cavity of the isolated joint of the joint preparation. Thereafter, an aliquot of perfusate is withdrawn from the outflow conduit and assayed for presence of the anti-inflammatory drug. Preferably, the amount of drug in the aliquot and the rate of flow of the perfusate from the isolated joint are also measured, so that total amount of the drug which leaks from the synovial cavity is determined.
4 Citations
20 Claims
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1. A joint preparation free of the host animal, comprising:
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(a) an isolated joint; (b) a perfusate for perfusing said isolated joint; (c) an oxygenator in fluid communication with the perfusate for oxygenating the perfusate; (d) an inflow conduit having a first end and a second end, the first end in communication with said isolated joint for introducing said perfusate into said isolated joint; (e) an outflow conduit having a first end and a second end, the first end in fluid communication with the isolated joint for receiving perfusate from the joint, the second end in fluid communication with the second end of the inflow conduit; and (f) a pump in communication with the inflow conduit or outflow conduit for pumping the perfusate through said isolated joint. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 17, 18, 19)
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13. A joint preparation in fluid communication with a host animal comprising:
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(a) an isolated joint; (b) a perfusate for perfusing said isolated joint; (c) an inflow conduit having a first end and a second end, the first end in fluid communication with the isolated joint and a second end in fluid communication with the host animal; (d) an outflow conduit for receiving the perfusate from said isolated joint, said outflow conduit having a first end in fluid communication with said isolated joint and a second end, said second ends of each of said inflow and outflow conduits being connected to the host animal to provide fluid flow from said first conduit through said joint and to said second conduit. - View Dependent Claims (14, 15, 20)
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Specification