Iontophoresis device

Details Iontophoresis device Iontophoresis device

2001-10-12

2003-11-04

Kennedy, Sharon (Department: 3762)

Surgery

Means for introducing or removing material from body for...

Infrared, visible light, ultraviolet, x-ray or electrical...

Reexamination Certificate

active

06643544

ABSTRACT:

TECHNICAL FIELD
The present invention relates to an iontophoresis device and energization method for transdermally or transmucosally delivering prostaglandins to blood vessels surrounding an affected part using electric driving force. In particular, the present invention relates to an iontophoresis device and an energization method, which exhibit good preservation stability for applying prostaglandin E1, or I2 or its derivatives to a patient with chronic artery obstruction (Berger's disease, obstructive arteriosclerosis), vibration disease, progressive systemic sclerosis or systemic lupus erythematodes and which allow for efficient control of delivery for a long period.
BACKGROUND ART
Iontophoresis is a transdermal-absorption promotion system using electricity as external stimulation. It is based on a mechanism that across an electric field generated between an anode and a cathode by energization, molecules with a positive charge move from the anode to the cathode while those with a negative charge move from the cathode to the anode, to generate force, which promotes penetration through a skin barrier by a drug molecule (See, Journal of Controlled Release, Vol. 18, 1992, pp. 213-220; Advanced Drug Delivery Review, Vol. 9, 1992, p.119; Pharmaceutical Research Vol. 3, 1986, pp. 318-326.).
On the other hands, prostaglandins are autacoids biosynthesized in a variety of biological cells, which have been clinically applied to various diseases such as geriatric diseases, thrombotic diseases, inflammatory immunoallergies and digestive ulcers. Since prostaglandins E1 and I2, among them, exhibit pharmacological actions such as potent vasodilator action and platelet-agglutination inhibiting action, they have been used treatment for ameliorating extremity ulcers in chronic arterial embolism such as Berger's disease and obstructive arteriosclerosis; ameliorating resting pain; ameliorating subjective symptoms associated with peripheral hematogenous disorder in vibration disease; recovering peripheral circulation function, neurological function or motor function in a variety of disorders; and ameliorating cutaneous ulcers in progressive systemic sclerosis and systemic lupus erythematodes.
Natural prostaglandins E1 and I2 have been developed as an injection due to their chemical stability and inactivation in a lung. Recently, a chemically and biologically stable injection has been developed by encapsulating prostaglandin E1 in lipid microspheres. On the other hand, recent investigation results have demonstrated that prostaglandins E1 and I2 may be chemically modified to be improved in their chemical and biological stability. It has lead to discovery of derivatives with more potent biological activities, resulting in development of drugs which may be orally administered.
However, as these prostaglandins have been investigated, it has been demonstrated that they are biologically controlled because they can exhibit various biological activities and provide potent pharmacological effects in a small amount. It has been, therefore, required to provide a system which can allow for strict drug-delivery control for achieving optimal drug efficacy of these prostaglandins in a limited disease while minimizing their side effects. For example, rimaprost, an oral prostaglandin E1 derivative, exhibits vasodilation, vascular-flow increasing, platelet-agglutination inhibiting and erythrocyte-deformability improving effects, so that it may be effective in ameliorating various ischemic symptoms such as ulcer, pain, frigidity and numbness associated with obstructive thromboanguitis, while excessive administration may causes side effects such as facial flush, tachycardia, extremity cyanosis and hemorrhage. These prostaglandins are, however, generally degraded by digestive fluid in a gastrointestinal tract, hydrolyzed by splitting enzymes in a gastrointestinal tract wall and inactivated mainly in a lung by first-pass effect. Furthermore, these prostaglandins have a short in vivo half life, so that drug efficacy cannot be adequately controlled in oral administration. Specifically, in oral administration, compliance may be improved in comparison with injection while a blood level control may be more difficult than injection administered by infusion. It is eminent particularly when the above prostaglandins, specifically prostaglandins E1 and I2 or their derivatives are continuously administered to enhance therapeutic effect. When a patient with a local lesion (in particular, an extremity lesion) such as cutaneous ulcer is treated via blood, for example, by an injection or oral drug, a drug may not be sufficiently delivered to the lesion to achieve satisfactory therapeutic effect.
As pharmaceutically practical dosage forms for these prostaglandins, there have been investigated, besides injections, oral formulations and suppositories for achieving systemic effect, transdermal and transmucous administration using ointments, creams, lotions and patches for achieving local effect. For example, Japanese Patent Application Laid-Open No.7-277985 has disclosed a transdermal absorption formulation to be applied to a cutaneous ulcer lesion. Since prostaglandins exhibit lower transdermal absorbability, a variety of transdermal-absorption promotion methods have been studied for improving absorbability. For example, Japanese Patent Application Laid-Open No. 3-83925 has disclosed the use of a transdermal-absorption promoter. In these existing formulations, local administration systems have been, however, dominant, aiming at direct administration on an ulcer lesion in a cutaneous surface. Furthermore, there have been no studies for a formulation by which long-term absorption may be achieved.
On the other hands, iontophoresis has been intensely investigated, which is a novel drug delivery system in place of an injection as an administration system for a drug requiring strict administration control. If an iontophoresis formulation by which absorption to the same level as that in an injection may be achieved and which allows a patient to administer a drug by him/herself is developed, home treatment may be realized. Precise control of an energization time in iontophoresis may allow any drug-absorption pattern to be achieved. In particular, it may lead to more effective drug treatment in a drug requiring administration control.
In terms of prostaglandin administration using such iontophoresis, Japanese Patent Application Laid-Open No. 9-235230, for example, has disclosed that combining prostaglandin E1 with a cyclodextrin may be improve drug stability and a transdermal absorption rate. International Patent Publications WO 98/29157 and WO 98/29158 have disclosed local administration of a prostaglandin for treating impotence by iontophoresis.
Conventional techniques such as ointments and creams are, however, related to a local-administration formulation mainly for treating diseases in a cutaneous surface without expecting sustained effects so that these techniques are not effective to diseases without ulcer. Iontophoresis for prostaglandins disclosed in Japanese Patent Application Laid-Open No. 9-235230 and International Patent Publications WO 98/29157 and WO 98/29158 is not for long-term delivery, may not allow us to strictly control absorption and thus is not sufficient to realize effective drug delivery.
DISCLOSURE OF THE INVENTION
It is an object of the present invention to provide an iontophoresis device and an energization method whereby prostaglandins can be effectively and continuously delivered via a skin or mucosa.
The inventors have intensely conducted investigation for achieving the above objective and have finally found that stabilizing means is incorporated in an iontophoresis device to improve preservation stability of prostaglandins, that constant-current supplying means is used to effectively and continuously administer via a skin ormucosa even a small amount of prostaglandin, and that constant-current supplying means may be combined with polarity inverting means to maintain electrificability for a long period s

Affiliated with

Also associated with

Rating

Iontophoresis device does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Iontophoresis device, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Iontophoresis device will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3146486