Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1999-04-26
2001-06-19
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S449000, C514S946000
Reexamination Certificate
active
06248348
ABSTRACT:
TECHNICAL FIELD
This invention relates to the transdermal delivery of drugs and other biologically active agents. More particularly, this invention relates to the transdermal delivery of drugs utilizing a novel combination of a permeation enhancer and a poly-N-vinyl amide to enhance flux, wearability, or stability of a transdermal device.
BACKGROUND ART
The transdermal route of parenteral delivery of drugs provides many advantages over other administrative routes, and transdermal systems for delivering a wide variety of drugs or other beneficial agents are described in U.S. Pat. Nos. 3,598,122; 3,598,123; 3,731,683; 3,797,494; 4,031,894; 4,201,21 1; 4,286,592; 4,314,557; 4,379,454; 4,435,180; 4,559,222; 4,573,995; 4,588,580; 4,645,502; 4,704,282; 4,788,062; 4,816,258; 4,849,226; 4,908,027; 4,943,435; and 5,004,610, for example. The disclosures of the above patents are incorporated herein by reference. In many instances, drugs that would appear to be ideal candidates for transdermal delivery are found to have such low permeability through intact skin that they cannot be delivered at therapeutically effective rates from reasonably sized systems.
In an effort to increase skin permeability, it has been proposed to pretreat the skin with various chemicals or to concurrently deliver the drug in the presence of a permeation enhancer. Various materials have been suggested for this purpose, as described in U.S. Pat. Nos. 3,472,931, 3,527,864, 3,896,238, 3,903,256, 3,952,099, 4,046,886, 4,130,643, 4,130,667, 4,299,826, 4,335,115,4,343,798, 4,379,454, 4,405,616 and 4,746,515, all of which are incorporated herein by reference; British Pat. No. 1,001,949; and Idson, Percutaneous Absorption, J. Pharm. Sci., Vol. 64, No. b6, June 1975, pp 901-924 (particularly 919-921).
Many permeation enhancers interact adversely with other components of transdermal devices. One problem is that many permeation enhancers are not compatible with medically acceptable contact adhesives. This can cause, among other problems, cohesive failure of adhesives. Additionally, the permeation enhancers can partition into other components in the system. This can cause devices to delaminate or it can cause instability of the device, thus shortening its shelf life.
Another problem related to adhesives of transdermal systems is the problem of adhesive failure resulting in water induced fall-off of the system. Adhesive failure may be caused by accumulation of the permeation enhancer at the skin-adhesive interface. As water accumulates on the skin, particularly during exercise or bathing, the interaction between the water and the permeation enhancer causes a soapy solution to form at the interface thereby causing the transdermal system to fall off.
This invention utilizes a novel combination of permeation enhancer(s) and a poly-N-vinyl amide. The novel combination produces a significant and surprising improvement in transdermal fluxes, drug utilization, storage stability, and improved adhesion over previous transdermal devices.
SUMMARY OF THE INVENTION
The present invention comprises a device for the transdermal administration, at a therapeutically effective rate, of a drug, which device comprises a reservoir comprising a therapeutically effective amount of drug, a skin permeation-enhancing amount of a permeation enhancer and a poly-N-vinyl amide; a backing on the skin-distal surface of the reservoir; and means for maintaining the reservoir in drug- and permeation enhancer-transmitting relation with the skin.
The present invention further comprises a device for the transdermal administration, at a therapeutically effective rate, of drug, which device comprises a first reservoir comprising a therapeutically effective amount of drug, a skin permeation-enhancing amount of a permeation enhancer and a poly-N-vinyl amide; a second reservoir comprising a permeation enhancer and a poly-N-vinyl amide, and optionally containing drug; a rate-controlling membrane between the first reservoir and the second reservoir; a backing on the skin-distal surface of the second reservoir; and means for maintaining the first and second reservoirs in drug- and permeation enhancer-transmitting relation with the skin.
The present invention also includes a method for the transdermal administration of a drug, the method comprising the step of placing a transdermal drug delivery device as described above onto the skin of a person.
The present invention also includes a method for increasing the transdermal flux of a drug from a transdermal device comprising incorporating into the drug containing reservoir of the transdermal devices described above, an effective amount of a poly-N-vinyl amide, wherein the device is used in the method for transdermal administration of a drug described above.
The present invention also includes a method for improving the adhesion of a transdermal delivery device comprising incorporating into the drug containing reservoir of the transdermal devices described above, an effective amount of a poly-N-vinyl amide, wherein the transdermal delivery device is used in the method for transdermal administration of a drug described above.
The present invention also includes a method for improving the stability of a transdermal delivery device comprising incorporating into the drug containing reservoir of the transdermal devices described above, an effective amount of a poly-N-vinyl amide, wherein the transdermal delivery device is used in the method for transdermal administration of a drug described above.
REFERENCES:
patent: 4291015 (1981-09-01), Keith
patent: 4438139 (1984-03-01), Keith
patent: 4466953 (1984-08-01), Keith et al.
patent: 4470962 (1984-09-01), Keith et al.
patent: 4472372 (1984-09-01), Keith et al.
patent: 4492685 (1985-01-01), Keith et al.
patent: 4579731 (1986-04-01), Fox, Jr. et al.
patent: 4626539 (1986-12-01), Aungst et al.
patent: 4668232 (1987-05-01), Cordes
patent: 4695465 (1987-09-01), Kigasawa
patent: 4781926 (1988-11-01), Hyon
patent: 4863970 (1989-09-01), Patel et al.
patent: 5176916 (1993-01-01), Yamanaka et al.
patent: 5230898 (1993-07-01), Horstmann et al.
patent: 5413776 (1995-05-01), Suzuki et al.
patent: 5556635 (1996-09-01), Istin et al.
patent: 5656286 (1997-08-01), Miranda et al.
patent: 5676968 (1997-10-01), Lipp et al.
patent: 5747065 (1998-05-01), Lee et al.
patent: 0 416 842 (1991-03-01), None
patent: 0 664 119 A2 (1995-07-01), None
patent: 4234314 (1992-08-01), None
patent: 93/07870 (1993-04-01), None
patent: WO 93/08795 (1993-05-01), None
patent: WO 95/18603 (1995-07-01), None
Hearney Linda M.
Landrau Felix A.
Nedberge Diane E.
ALZA Corporation
Bates Owen J.
Ghali Isis
Page Thurman K.
Stone Steven F.
LandOfFree
Incorporating poly-N-vinly amide in a transdermal system does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Incorporating poly-N-vinly amide in a transdermal system, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Incorporating poly-N-vinly amide in a transdermal system will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2513525