Drug testing system with bio-artificial liver

Abstract

A drug testing system using a liver-slice culture apparatus. The apparatus has a chamber with plasma and gas valves, animal liver slices being positioned securely in the chamber so as to maximize the surface area of liver slices exposed to the culture medium. Plasma is supplied to the chamber so that it rises to contact the liver slices, and is alternately removed from contacting the liver slices. Gas is supplied to the top of the chamber. The system also includes a reservoir for containing media entering and exiting the chamber. Methods are provided for assessing the toxicity of a drug or drug candidate.

Description

BACKROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] The invention relates to a drug testing system with a biological artificial liver and, more particularly, a bioreactor for evaluation, detection and testing of drug candidates, drugs and drug metabolites. [0003] 2. Discussion of Related Art [0004] In 2001, the average cost to develop a new drug exceeded $800 million, according to a study by the Tufts Center for the Study of Drug Development. Of this, approximately $16 million on average per company was used for pre-clinical research. Reduction of testing time and cost in drug development is therefore a critical factor to the survival of most pharmaceutical companies. In addition, since there is usually more than one company competing in the same drug arena, any competitive advantage would be welcome. A major portion of drug development costs is borne during the FDA approval process. However, much of this cost cannot be managed in the same way that pre-clinical costs ...

AI Technical Summary

Benefits of technology

[0010] It is one object of the present invention to provide a system to test the toxicity of a potential drug candidate and its metabolites.

Problems solved by technology

A major portion of drug development costs is borne during the FDA approval process.

However, much of this cost cannot be managed in the same way that pre-clinical costs can.

Since the liver metabolizes most drugs, liver damage is of great concern.

However, these conventional tests have particular disadvantages, such as individual variation, high costs to use large animals, and loss of naturally existing characteristics of liver in situ.

However, with these models cell-to-cell connective interactions cannot be maintained for a desired length of time.

This leads to failure of the testing scheme.

However problems remain with respect to maintaining the functionality of the individual cell lines used in these devices.

It has been found that over time these cells lose specific functions.

Various aspects of these devices represent improvements over pre-existing technology, but they still have particular disadvantages.

The effectiveness of these devices, all of which use individual hepatocytes, is limited due to the lack of cell-to-cell interactions, which characterize the liver in its in vivo state.

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