Method for measuring permeability coefficient of oral drug by using hollow fiber membrane

Abstract

The invention discloses a method for measuring permeability coefficient of oral drugs by using a hollow fiber membrane. The method comprises the following steps: (1) preparing a receptor solution; (2) preparing a donor solution; (3) immersing a hollow fiber membrane tube with one end sealed in a lecithin solution and taking out the tube; (4) connecting an open end of the hollow fiber membrane tube treated in the step (3) with a connecting pipe; (5) adding the receptor solution into the treated hollow fiber membrane tube through the connecting pipe; and (6) immersing the hollow fiber membrane tube with receptor solution in a container with donor, wherein the receptor solution surface is lower than the donor solution surface; and permeating for 0.55 h, sampling from the receptor solution, determining drug concentration in the receptor solution, and calculating permeability coefficient. The invention has advantages of simple device, easy installation, fast test preparation, rapid analysis and high efficiency; besides, advanced detection equipment is employed to achieve high-throughput determination of drug permeability coefficient, so as to adapt to requirements of high throughput drug screening and realize wide scope of drug application.

Description

technical field [0001] The invention relates to a method for measuring the permeability coefficient of oral medicine. Background technique [0002] Drug screening is a step in the modern drug development process to detect and obtain compounds with specific physiological activity. It is a process of selecting compounds with high activity on a specific target from a large number of compounds or new compounds through standardized experimental methods. With the advent of combinatorial chemistry, the synthesis speed of candidate compounds has been greatly accelerated, and the absorption, distribution, metabolism, excretion and toxicity of candidate compounds in the early stage of research and development can be analyzed in a high-throughput manner. Screening and comprehensive evaluation of compounds as early as possible has become the leading trend of innovative drug research, but this stage also faces the problems of a large variety of test compounds, a variety of experimental p...

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But this method cultures Caco-2 cells for up to 21 days and requires professional skills

In recent years, the PAMPA method has been widely used as a higher-throughput in vitro screening method. The device used is called a "sandwich" device, that is, the test cavity is divided into upper and lower layers by means of an artificial membrane coated with lecithin. , the upper layer is the drug solution (donor fluid) layer, and the lower layer is the acceptor fluid (acceptor fluid) layer. By measuring the concentration of the donor fluid and the concentration of the acceptor fluid after permeation for a certain period of time, the permeability coefficient of the drug is obtained, and then the drug in vivo is predicted. Absorption, but because there is an undisturbed layer close to the membrane, especially on the lower side of the membrane, the undisturbed layer is as high as 1900 μm, and the thickness of the undisturbed layer in which the drug permeates in human blood vessels is only 30-100 μm, so the PAMPA There is a certain difference between the measurement results and the actual results; in addition, the PAMPA method needs to measure the concentration of the donor fluid and the acceptor fluid, the whole equilibrium and analysis time is long, the operation is cumbersome, and the matching consumables are expensive

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