Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
2002-06-25
2004-07-06
Dodson, Shelley A. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S484000, C514S937000, C514S938000
Reexamination Certificate
active
06759056
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the discovery of a transdermal delivery system that can deliver high molecular weight pharmaceuticals and cosmetic agents to skin cells. A novel transdermal delivery system with therapeutic and cosmetic application and methods of use of the foregoing is disclosed.
BACKGROUND OF THE INVENTION
The skin provides a protective barrier against foreign materials and infection. In mammals this is accomplished by forming a highly insoluble protein and lipid structure on the surface of the corneocytes termed the cornified envelope (CE). (Downing et al.,
Dermatology in General Medicine
, Fitzpatrick, et al., eds., pp. 210-221 (1993), Ponec, M.,
The Keratinocyte Handbook
, Leigh, et al., eds., pp. 351-363 (1994)). The CE is composed of polar lipids, such as ceramides, sterols, and fatty acids, and a complicated network of cross-linked proteins; however, the cytoplasm of stratum corneum cells remains polar and aqueous. The CE is extremely thin (10 microns) but provides a substantial barrier. Because of the accessibility and large area of the skin, it has long been considered a promising route for the administration of drugs, whether dermal, regional, or systemic effects are desired.
A topical route of drug administration is sometimes desirable because the risks and inconvenience of parenteral treatment can be avoided; the variable absorption and metabolism associated with oral treatment can be circumvented; drug administration can be continuous, thereby permitting the use of pharmacologically active agents with short biological half-lives; the gastrointestinal irritation associated with many compounds can be avoided; and cutaneous manifestations of diseases can be treated more effectively than by systemic approaches. Most transdermal delivery systems achieve epidermal penetration by using a skin penetration enhancing vehicle. Such compounds or mixtures of compounds are known in the art as “penetration enhancers” or “skin enhancers”. While many of the skin enhancers in the literature enhance transdermal absorption, several possess certain drawbacks in that (i) some are regarded as toxic; (ii) some irritate the skin; (iii) some on prolonged use have a thinning effect on the skin; (iv) some change the intactness of the skin structure, resulting in a change in the diffusability of the drug; and (v) all are incapable of delivering high molecular weight pharmaceuticals and cosmetic agents. Clearly there remains a need for safe and effective transdermal delivery systems that can administer a wide-range of pharmaceuticals and cosmetic agents to skin cells.
BRIEF SUMMARY OF THE INVENTION
In aspects of the invention described below, transdermal delivery systems are provided that can be used to administer pharmaceuticals and cosmetic agents of various molecular weights. In several embodiments, the transdermal delivery system comprises a novel formulation of penetration enhancer and aqueous adjuvant that enables the delivery of a wide range of pharmaceuticals and cosmetic agents having molecular weights of less than 100 daltons to greater than 500,000 daltons. For example, embodiments of the transdermal delivery system described herein can be used to deliver a therapeutically effective amount of a non-steroidal anti-inflammatory drug (NSAID), a capsaicin or Boswellin containing pain-relief solution, or several different collagen preparations. Methods of making and using the transdermal delivery devices of the invention for the treatment and prevention of human disease and cosmetic condition are also provided.
Accordingly, in one embodiment a transdermal delivery system is provided that comprises an ethoxylated lipid, an alcohol mixed with the ethoxylated lipid so as to form a penetration enhancer, an aqueous adjuvant mixed with the penetration enhancer, wherein the aqueous adjuvant is a plant extract from the family of Liliaceae, and a delivery agent mixed with the aqueous adjuvant and the penetration enhancer. In some aspects of this embodiment, the ethoxylated lipid is a vegetable or animal oil having at least 20 ethoxylations per molecule. In other aspects of this embodiment, about 0.1% to 40.0% by weight or volume is ethoxylated lipid. Other embodiments of the invention include the transdermal delivery system described above wherein about 0.1% to 15% by weight or volume is alcohol or wherein about 0.1% to 85% by weight or volume is
Aloe Vera
. Still more embodiments of the invention have a ratio of ethoxylated lipid:alcohol:aqueous adjuvant selected from the group consisting of 1:1:4, 1:1:14, 3:4:3, and 1:10:25.
Desirably, the transdermal delivery systems described above have delivery agents that are molecules having a molecular weight of less than 6,000 daltons. In some embodiments, the transdermal delivery system described above has a delivery agent that is one or more of the compounds selected from the group consisting of capsaicin, Boswellin, non steroidal anti-inflammatory drug, and collagen. Preferably, however, the delivery agent is a molecule having a molecular weight of greater than 6,000 daltons. Additional embodiments include an apparatus comprising a vessel joined to an applicator and the transdermal delivery system described above incorporated in the vessel. Applicators in embodiments of the invention can be a roll-on or a sprayer.
In another aspect, a transdermal delivery system is provided which comprises an ethoxylated oil, an alcohol mixed with the ethoxylated oil so as to form a penetration enhancer, an Aloe extract mixed with the penetration enhancer, and a therapeutically effective amount of capsaicin or NSAID or both mixed with the penetration enhancer and Aloe extract. In some embodiments of this aspect, the therapeutically effective amount of capsaicin is by weight or volume 0.01% to 5.0% capsaicin or 1.0% to 13% oleoresin capsicum. In other embodiments of this aspect, the transdermal delivery system further includes by weight or volume 0.1% to 10% Boswellin. As above, an apparatus having a vessel joined to an applicator that houses the transdermal delivery system is also an embodiment and preferred applicators include a roll-on or a sprayer.
Several methods are also within the scope of aspects of the invention. For example, one approach involves a method of reducing pain or inflammation comprising the step of administering the transdermal delivery system described above to a subject in need and monitoring the reduction in pain or inflammation. Additional methods of the invention include approaches to treat cancer and Alzheimer's disease. For example, a method of treating or preventing cancer and Alzheimer's disease can comprise the step of identifying a subject in need of a COX enzyme inhibitor and administering the transdermal delivery system described above to the subject.
In addition to the delivery of low and medium molecular weight delivery agents, several compositions that have high molecular weight delivery agents (e.g., collagens) and methods of use of such compositions are embodiments of the invention. For example, one embodiment concerns a transdermal delivery system comprising an ethoxylated oil, an alcohol mixed with the ethoxylated oil so as to form a penetration enhancer, an Aloe extract mixed with the penetration enhancer, and a therapeutically effective amount of collagen mixed with the penetration enhancer and Aloe extract.
In different embodiments of this transdermal delivery system, the collagen has a molecular weight less than 6,000 daltons or greater than 6,000 daltons. Thus, in certain embodiments, the collagen can have an approximate molecular weight as low as 2,000 daltons or lower. In a certain embodiment, the molecular weight is from about 300,000 daltons to about 500,000 daltons. Further, these transdermal delivery systems can have a therapeutically effective amount of collagen by weight or volume that is 0.1% to 50.0% and the collagen can be Hydrocoll EN-55 when the therapeutically effective amount by weight or volume is 0.1% to 50.0%; the collagen can be Solu-Coll when the the
Dodson Shelley A.
Knobbe Martens Olson & Bear
Oryxe
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