Methods for evaluating efficacy of anti-inflammatory on drugs on

Surgery – Miscellaneous – Methods

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604 27, 604 28, 435 12, A61B 0019

Patent

active

057996601

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 Thereafter, an aliquot of perfusate is withdrawn from the outflow conduit and assayed for presence of the anti-inflammatory drug.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.

REFERENCES:
patent: 3914954 (1975-10-01), Doerig
patent: 4192302 (1980-03-01), Boddie
"Physiologic Responses of a Novel Isolated Joint Model" by Bertone, et al., (short poster page) Transactions of the 41st Annual Meeting of Orthopaedic Research Society, Feb. 1995, p. 796.
"Blood Flow, Permeability, and O.sub.2 Metabolism of Innervated or Denervated Isolated Joints in an IL-1 Model" (short poster page) Transactions of the 42nd Annual Meeting of Orthopaedic Research Society Feb. 1996 p. 429.
"Evaluation of Vascular Compliance and Vasoconstrictive Reactions in Amputated Hindlimbs of Rats" by Ono, et al., Journal of Orthopaedic Research, vol. 13, pp. 375-381, May 1995.
"Evaluation of Starling Forces in the Equine Digit", Allen, et al., Journal of Applied Physiology, vol. 64, No. 4, pp. 1580-1583, Apr. 1988.

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