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Composition and device structure for iontophoresis

Inactive Publication Date: 2004-04-15
HISAMITSU PHARM CO INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, synthesized narcotic analgesics have only narrow therapeutic range because they have not only a potent analgetic action but also cause significant adverse reactions such as respiratory depression.
The excessive dosing, however, cause the adverse reactions such as anorexia while they are needed to be frequently administered repetitively to increase their therapeutic effect.
Most of the drugs are known, however, to be not absorbable since they are decomposed by digestive juices in the gastrointestinal tracts or hydrolized by decomposing enzymes of the gastrointestinal walls.
Therefore, as for administration of these drugs, injection is usually conducted to avoid adverse reactions and because adequate efficacy control cannot be expected by oral administration.
Injections, however, give much pain to patients and become a burden since they can not be self-administered, even more so particularly in the case of the above described Calcitonin which is needed to be frequently administered repetitively.
However, it is known that the materials in the preparation to control the pH include the ion species which have the similar polarity to the drug (competitive ions) causing to reduce the drug delivery ratio substantially.
The organic acids are, however, polar materials similar to prostaglandin E.sub.1, therefore they can not avoid competition with the drugs when used together.
These pH adjusting materials or buffer agents have approximately similar or below the molecular weight of the drugs, therefore they have the problem that they lower the drug delivery rate and reduce the drug absorption when being existed together with drugs.
These operation of pH adjustment is, however, complicated and not practical in terms of quality assurance owing to drug adhesion to the resin, or the like.
Thus, at the cathode side, pH of the electrically conductive layer rapidly increases during energizing resulting in reduction of the drug delivery rate and therefore extreme reduction of drug absorption.
This changes dissociation of the drug and affects the drug absorption particularly with long time energizing with current.
No solution has been found yet for means to control those pH changes occurred during energizing with current.
The function is, however, limited to the drug release control and there is no description about the composition for iontophoresis for effective delivery of the drug.

Method used

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  • Composition and device structure for iontophoresis
  • Composition and device structure for iontophoresis
  • Composition and device structure for iontophoresis

Examples

Experimental program
Comparison scheme
Effect test

experimental example 1

A Preparation Example when Aminoalkylmethacrylate Copolymer E is Used as a pH Adjusting Agent

[0133] Experimental Example 1 shows a preparation example when aminoalkylmethacrylate copolymer E is used as a pH adjusting agent. The pH of a preparation in this Experimental Example was adjusted to around 4.5-6.5. In this step, hydrochloric acid was charged to add chloride ion as a reactant with an active electrode.

example 1

[0134]

5 Component Content (%(w / w)) Fentanyl citrate 1.00 Agar 1.00 Aminoalkylmethacrylate copolymer E 5.60 Hydrochloric acid 0.55 Methyl para-oxybenzoate 0.20 Distilled water for injection Appropriate amount Total 100.00

[0135] Fentanyl citrate, aminoalkylmethacrylate copolymer E and hydrochloric acid were added to distilled water and stirred until these were dissolved. Further, agar and methyl para-oxybenzoate were added with stirring followed by heating at about 90.degree. C. to dissolve. After cooled near to about 60.degree. C., about 0.8 g of this solution was charged into an electrode cup made of polyethylene terephthalate (thereinafter, abbreviated as PET). The pH of the prepared formulation was 4.9.

experimental example 2

Influence of Aminoalkylmethacrylate Copolymer E Affecting Aniontophoresis-Releasing Test of Fentanyl Citrate

[0140] Next, using the above described formulations (Example 1 and Comparative Example 2), a releasing test by iontophoresis was performed. Using a sideways type cell in the releasing test, 3% (w / w) agarose gel (3 mm) was used as a release control layer. The experiment was conducted at a room temperature, and after electrically energizing with current for 1 hr, the drug amount transferred into a receptor layer was measured by high-performance liquid chromatography. The electrically energizing with current was performed at 0.2 mA / cm.sup.2 constant-current for 1 hr of the total energizing time using direct-current energizing for pulse depolarization (50 kHz frequency, 50% duty) by a short-circuit switch. FIG. 2 is a graph showing the results of the releasing test of fentanyl citrate by iontophoresis. As clarified from FIG. 2, the releasing amount of fentanyl by ionyophoresis is ...

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PUM

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Abstract

Device structure 100 for iontophoresis provides electrode 101 and electrically conductive layer 102. Electrically conductive layer 102 contains active ingredient D and basic water swelling methacrylate copolymer P1 and / or acidic water swelling methacrylate copolymer P2. Electrode 101 and electrically conductive layer 102 are placed into a hollow of backing 103 and electrode terminal 104 is connected to electrode 101 through backing 103. Adhesive layer 105 is set around backing 103, and liner 106 to be removed when using the device, is placed so as to cover the hollow of backing 103.

Description

BACKGROUND OF INVENTION[0001] The present invention relates to a composition for iontophoresis and a device structure using it, more specifically, a composition for iontophoresis to deliver an active ingredient to an organism safely and efficiently using electric driving power and a device structure using it.[0002] Iontophoresis is an accelerating system for transdermal absorption using electricity as an outside stimulus. The principal is that it accelerates penetration of the drug's molecules through the skin barrier based on the moving power of positively charged molecules and negatively charged molecules from the anode to the cathode and from the cathode to the anode, respectively, in the electric field generated between the anode and the cathode mainly by energizing with current (see Journal of Controlled Release, vol. 18, 213-220, 1992; Advanced Drug Delivery Review, 119, 1992; Pharmaceutical Research, vol. 3, pp. 318-326, 1986).[0003] Iontophoresis is a method of making the ch...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K47/32A61N1/30
CPCA61K9/0009A61K9/0014A61N1/0448A61N1/0444A61K47/32A61P25/04A61P9/06A61N1/30
Inventor ADACHI, HIROTOSHIKUZUMAKI, NORIYUKIARIMOTO, TETSUYAHIGO, NARUHITO
Owner HISAMITSU PHARM CO INC
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