Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
2000-06-19
2004-04-20
Hartley, Michael G. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S443000, C424S447000, C424S449000, C424S484000, C424S486000, C424S487000, C516S931000, C516S931000, C516S931000
Reexamination Certificate
active
06723337
ABSTRACT:
BACKGROUND OF THE INVENTION
This application is a 371 of PCT/KR 98/00295, filed Sep. 25, 1998.
1. Field of the Invention
The invention herein relates to a transdermal drug delivery system for anti-inflamnatory analgesic agent comprising diclofenac diethylammonium salt, wherein a backing film, a matrix containing active ingredients, a release liner which is removed before application onto the skin are laminated therein. More particularly, the invention herein relates to a transdermal drug delivery system for anti-inflammatory analgesic agent comprising diclofenac diethylammonium salt, wherein the transdermal penetration and adhesion of the patch to the body are enhanced by means of a matrix layer which comprises a diclofenac diethylamnmoniun salt as active ingredient in addition to non-aqueous acrylic polymer as adhesive constituent, non-ionic surfactant as absorption enhancer, terpene and dissolution assistant, and the volatile and non-volatile constituents of the composition are separately applied therein for significantly reducing the manufacturing time thereof.
2. Description of the Prior Art
Diclofenac salt, one of non-steroid anti-inflammatory drugs (NSAIDs), shows therapeutic efficacy by means of inhibiting a biochemical reaction path which is necessary for the biosynthesis of a pain inducer, prostaglandin. Diclofenac is a drug which has the effects of pain relief, antifebrile and anti-inflammation and is widely applicable in rheumatic arthritis, osteoarthritis, spastic spondylitis, acute gout, and inflammation or gout of lesion after operation. However, if diclofenac is orally administered for a long period of time, a peptic ulcer is induced along with other side effects such as anemia by hemorrhage. In order to reduce such side effects on stomach, which is most problematic for an oral dosage form, a research into the method of formulating the same into a transdermal administration matrix has actively been in progress. In general, the subject matters of the research done thus far can be classified into a topical dosage form and a patch (transdermal drug delivery system).
The prior art relating to the topical dosage form is disclosed in U.S. Pat. Nos. 4,537,776. 5,350,769, 5,422,102, and European Unexamined Patent No. 0,428,352 A1 and International Unexamined Patent No. WO 92/20377. The aforementioned prior art relates mainly to get, emulsion and ointment, which are directly applied onto the skin without a backing film for sealinrg the active ingredients. As such, the topical dosage is inconvenient in that the pharmaceutical composition may smear on clothe, result in variable application dosage, emit odor and necessitate a multiple daily application.
On the other hand, a patch has a constant dosage for application without the inconvenience of smearing on clothe or multiple applications. A patch can generally be classified into reservoir and matrix types. As for the reservoir type, the pharmaceutical composition of gel, emulsion or ointment can be used but cannot be applied to joints and curved body parts. On the other hand, a matrix type is convenient in that it can be applied to anywhere on the body depending on the properties of a backing film and adhesive constituent. Although the matrix can be applied to the skin for a long period of time without irritation, a difficulty arises in the system architecture in that an absorption enhancer must be added in order to maintain a continuous transdermal penetration.
With respect to the patch of a matrix type, for enhancing the transdermal penetration, U.S. Pat. No. 4,738,848 used diclofenac in a free acid form converted from sodium diclofenac salt via such organic acids as citric acid. In Korean Unexamined Patent No. 94-23471, the transdermal penetration of the accumulated diclofenac was increased to 180 &mgr;g/cm
2
·day by using a composition comprising hydroxy ethyl pyrrolidone or hydroxy ethyl piperidine as absorption enhancer.
Further. Korean Unexamined Patent No. 93-1896 disclosed a sodium diclofenac salt plaster comprising an absorption enhancer of menthol and propylene glycol, and a hydrophilic substrate having a water-soluble polymer. In the aforementioned prior art, the examples of water-soluble polymers generally used in the plaster as substrate constituents include polyacrylic acid, sodium polyacrylate, carboxyvinyl polymer, sodium carboxymethyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol and gelatin. The solid part of the plaster, comprising the water-soluble polymer as main substrate, moisturizer, humectant lysosome, inorganic filler, viscosity controller, cross-linking agent, active ingredient, was manufactured by a process of mixing of the combinants, stirring and then surface application. However, if the surface application of all the pharmaceutical compositions is carried out at once with the plaster containing volatile menthol and propylene glycol, the prolong drying process at a low temperature range of 40~50° C. was necessary after application. Further, in the case of such solid plaster, it was too thick to the point that adhesion sensation was unduly excessive with poor adhesion, which in turn resulted in easy detachment.
SUMMARY OF THE INVETION
The invention herein uses diclofenac diethylanimonium salt as active ingredient and non-aqueous acrylic polymer with superior solubility in organic solvents instead of a water-soluble adhesive constituent. In order to increase absorption, the invention includes a non-ionic surfactant and terpene at a certain mixing ratio. For increasing the drug concentration, the invention includes a dissolution assistant in a certain amount so that the transderrnal drug delivery of the active ingredient is more than doubled as compared to Korean Unexamined Patent No. 94-23741. Therefore, the objective of the invention herein is to provide a transdermal drug delivery system comprising diclofenac diethylanunonium salt, wherein the transdermal drug delivery of the active ingredient is more than far more superior than that of the prior art without undue deterioration of adhesion to the body even for a long-term application.
Further, as for the matrix layer of the present invention, unlike other plasters of the prior art, the adhesive layer (
2
a
′) is formed by applying a non-volatile constituent among the total pharmaceutical composition onto one side of the backing film, after which is dried for a short period time at a high temperature. Thereafter, a volatile absorption enhancer layer (
2
b
) is formed by separately applying volatile constituents comprising a dissolution assistant and a compound such as terpene for imparting cool sensation upon initial application to the body. Another adhesive layer (
2
a
″) is formed onto the release liner (
3
) by the aforementioned method, after which is laminated onto the upper portion of the volatile absorption enhancer layer (
2
b
), thereby forming the matrix layer (
2
) herein. Consequently, another objective of the present invention lies in providing a manufacturing method of a transdermal drug delivery system having diclofenac diethylammonium salt, wherein the manufacturing time is significantly reduced.
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patent: 0 428 352 (1990-11-01), None
patent: 0 524 582 (1992-07-01), None
patent: 0 581 587 (1993-07-01), None
patent: 0 600 395 (1993-11-01), None
patent: 0682942 (1995-11-01), None
patent: 2192539 (1988-01-01), None
patent: 4193826 (1992-07-01), None
patent: WO 92/20377 (1992-11-01), None
Choi Young Kwon
Lee Heon Han
Park Chul Min
Shim Yong Ho
Song Jin Deog
Gollamudi Sharmila S
Hartley Michael G.
Samyang Corporation
Thorpe North & Western LLP
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