Electroresponsive hydrogel and physiologically active substance release control system

• US 5,152,758 A
• Filed: 07/23/1990
• Issued: 10/06/1992
• Est. Priority Date: 08/04/1989
• Status: Expired due to Fees

• Current Assignee: Senju Pharmaceutical Company Limited
• Original Assignee: Senju Pharmaceutical Company Limited
• Inventors: Ohtori, Akira, Kaetsu, Isao, Morita, Yasushi
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): Bockelman, Mark
• Application Number:
  US07/556,332
• Time in Patent Office: 806 Days
• Field of Search: 604/20, 604/50, 604/65-67, 604/246, 604/890.1, 604/891.1, 604/892.1, 128/DIG. 12, 128/639, 128/632
• US Class Current: 604/890.1
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

An electroresponsive hydrogel produced by alkali hydrolysis of a copolymer comprising N-isopropylacrylamide, an ionic monomer and a crosslinking agent; and a physiologically active substance release control system comprising a biosensor, an amplifier and an electroresponsive hydrogel containing physiologically active substance are disclosed. The hydrogel of the present invention is capable of releasing a physiologically active substance alone in an amount corresponding to the applied voltage with excellent reproducibility by contracting and reswelling in good response to the loading and unloading of an external stimulation voltage, it can be advantageously used in a physiologically active substance release control system capable of releasing an essential physiologically active substance in a necessary amount according to changes in physiological conditions. Also, the physiologically active substance release control system of the present invention using this hydrogel is useful for the treatment of various diseases including diabetes mellitus.

Claims

1. A physiologically active substance release control system which comprises:

a biosensor for sensing the presence of an indicator chemical substance in vivo and for generating an electrical output voltage dependent upon the concentration of said indicator chemical substance in vivo,

an amplifier for receiving said electrical output voltage and for amplifying said voltage and providing an output signal corresponding thereto, and

an electroresponsive hydrogel containing a physiologically active substance for receiving said output signal from said amplifier and for contracting in response thereto, thereby releasing said physiologically active substance therefrom.

2. A physiologically active substance release control system as claimed in claim 1 wherein the biosensor is an ion sensitive field effect transistor having an enzyme immobilized on its element.

3. A physiologically active substance release control system as claimed in claim 2 wherein the indicator chemical substance is a substance capable of reacting with said enzyme to produce hydrogen ions.

4. A physiologically active substance release control system as claimed in claim 1 wherein the biosensor is produced by coating a photocuring resin mixed with a particular enzyme on said element by dipping and immobilizing it by near ultraviolet irradiation.

5. A physiologically active substance release control system as claimed in claim 1 wherein the amplifier is capable of amplifying the voltage from the biosensor at a constant rate of about 1000 fold.

6. A physiologically active substance release control system as claimed in claim 1 wherein the electroresponsive hydrogel is prepared by the alkali hydrolysis of a copolymer comprising N-isopropylacrylamide, an ionic monomer and a crosslinking agent.

7. A physiologically active substance release control system as claimed in claim 1 wherein the electroresponsive hydrogel is produced by hydrolyzing a copolymer comprising 100 parts by weight of N-isopropylacrylamide, 5 to 50 parts by weight of an ionic monomer and 2 to 15 parts by weight of a crosslinking agent.

8. A physiologically active substance release control system as claimed in claim 1 wherein the electroresponsive hydrogel is produced by hydrolyzing a copolymer comprising 100 parts by weight of N-isopropylacrylamide, 10 to 40 parts by weight of an ionic monomer and 5 to 10 parts by weight of a crosslinking agent.

9. A physiologically active substance release control system as claimed in claim 1 wherein the physiologically active substance is insulin.