Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Matrices
Patent
1994-08-11
1998-11-03
Webman, Edward J.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Matrices
424484, 514944, A61K 910, A61K 4742, A61K 4736
Patent
active
058305068
DESCRIPTION:
BRIEF SUMMARY
This invention concerns a method for producing a drug system for delivering a drug or other agent for the treatment of a condition in a controlled release manner.
Most known `controlled-release` drug systems are constant slow-release mechanisms (U.S. Pat. No. 4,145,410). These systems do not react to any inherent substances in the body to release the drug appropriately in response to that substance, ie. there is no feedback mechanism. Feedback mechanisms have been suggested to be of interest in vivo to maintain general homeostasis.
U.S. Pat. No. 4,348,387 discloses a feedback controlled insulin delivery system wherein glucose-insulin conjugates are displaced from glucose binding sites on a binding molecule by free glucose. The conjugated insulin retains its biological activity once released. However, it is not known whether other agents or drugs can be so conjugated or whether such a conjugated form of any drug or other agent would be effective.
The present invention provides a controlled drug delivery system for the controlled release of an unconjugated drug or other agent.
According to the present invention there is provided a method for producing a drug system for delivering a drug for the treatment of a condition, comprising immobilising a drug or other agent in a bio-compatible matrix containing at least one receptor for a physiological substance which will be in the environment of the matrix when administered, said receptor being activated in response to the levels of said physiological substance to effect a conformational change in the matrix allowing mobilisation and release of the drug into the environment.
The agent may comprise a naturally occurring biological agent, for example, a hormone, which may, of course, be insulin, as in U.S. Pat. No. 4,348,387, but now in unconjugated form. Because there is now no need for conjugation, other hormones or drugs which it may not be possible to conjugate or which will not work in the system of U.S. Pat. No. 4,348,387 even if they can be conjugated, or which may be physiologically ineffective or less effective or even harmful when conjugated, may be used according to the invention.
The receptor may be a binding macromolecule, for example, a lectin, which may be concanavalin A, a lectin produced from the jack bean.
The receptor may reversibly bind the physiological substance, which may be a carbohydrate, preferably glucose, or a carbohydate containing glucose moieties, such as dextran.
Insulin, or any other agent or drug, may be immobilised in the matrix when terminal glucose molecules on dextran bind to concanavalin A to form a gel.
The conformational change in the matrix may be brought about by the displacement of terminal dextran-glucose molecules from the receptor by free glucose in the physiological environment which may of course be blood or other tissue fluid.
The conformational change may be an ungelling of the matrix allowing mobilisation and release of the insulin or other agent or drug.
The invention will be further apparent from the following description with reference to the several figures of the accompanying drawings, which show, by way of example only, one form of the system embodying same.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a diagrammatical representation of a concanavalin-A molecule binding glucose;
FIG. 2 shows a diagramatical representation of the delivery system, in an inactive form;
FIG. 3 shows a diagramatical representation of the delivery system, in an active form;
FIG. 4 shows the drug system of FIG. 2 enclosed in a bio-compatible lattice; and
FIGS. 5 to 7 show in vitro experimental results of the drug system.
Referring now to the drawings, it will be seen that the drug delivery system is based on a concanavalin-A molecule 11. Each concanavalin-A molecule 11 has four binding sites 12 specific for sugars, with a high affinity for glucose 13 (FIG. 1). The binding of glucose 13 to the binding site 12 is, however, reversible.
The inactive form of the drug system comprises (FIG. 2) glucose present as terminal glucose moiet
REFERENCES:
Targeted Drug Delivery, Rudolph L. Juliano, Springer-Verlag Berlin Heidelberg, 1991, pp. 149, 151-154.
De Montfort University
Webman Edward J.
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