Claims
- 1. A transdermal device suitable for administration of a pharmaceutically active agent to the systemic circulation through a de-epithelialized skin lesion, said device including a reservoir for the active agent, said reservoir being selected from the group consisting of an inert porous matrix in which the active agent is dispersed and a chamber containing said agent in a form selected from the group consisting of a solid, an unsaturated solution, a saturated solution, a supersaturated solution and a suspension, said device further including a selective membrane positioned intermediate said reservoir and said de-epithelialized skin so as to be in contact with said de-epithelialized skin when the device is in use, said selective membrane having pores sized so as to block passage of proteolytic enzymes that exude from the de-epithelialized skin while permitting passage of active agent to the skin;wherein said selective membrane is cellulose acetate, nitrocellulose, polytetrafluoroethylene, or a swellable hydrogel.
- 2. A device as claimed in claim 1, wherein said reservoir is an inert porous matrix that is an adhesive.
- 3. A device as claimed in claim 1, wherein the pharmaceutically active agent is of smaller molecular weight than any proteolytic enzyme in an exudate from the de-epithelialized lesion.
- 4. A device as claimed in claim 1, wherein said reservoir is an inert porous matrix in which the active agent is dispersed.
- 5. A device as claimed in claim 1, wherein said device prevents passage of pharmaceutically active agents having a molecular weight of greater than 50,000 Daltons.
- 6. A device as claimed in claim 1, wherein said device prevents passage of pharmaceutically active agents having a molecular weight greater than 100,000 Daltons.
- 7. A device as claimed in claim 1, wherein said pore vary in pore size across a depth of said Selective membrane.
- 8. A device as claimed in claim 1, further including a pre-filter positioned in use between one of said selective membrane and said inert porous matrix and the de-epithelialized skin, said pre-filter having larger pore size than the selective membrane or inert porous matrix.
- 9. A device as claimed in claim 8, wherein said pre-filter comprises a material selected from a group consisting of cellulose ester, polypropylene and polyvinylidene difluoride.
- 10. A device as claimed in claim 1, further including means to inhibit activity of proteolytic enzymes.
- 11. A device as claimed in claim 10, wherein said device includes at least one inhibitor of a proteolytic enzyme.
- 12. A device as claimed in claim 11, wherein said at least one inhibitor is present in said reservoir.
- 13. A device as claimed in claim 11, wherein said inhibitor of proteolytic enzyme is dispersed in said selective membrane.
- 14. A device as claimed in claim 11, wherein said at least one inhibitor inhibits at least one enzyme selected from a group consisting of aminopeptidase, carboxylpeptidase, endopeptidase, metalloprotease, dipeptidylpeptidase, elastase, collaginase, plasmin and plasminogen activator.
- 15. A device as claimed in claim 14, wherein said at least one enzyme inhibitor is selected from a group consisting of bestatin, phosphoramydon, a2-macroglobulin, sodium ethylenediaminetetracetatic acid, amastatin anti-plasmin, cholate, and analogs of cholate.
- 16. A device as claimed in claim 1, wherein said pharmaceutically active agent is encapsulated in microspheres of an inert porous polymer material.
- 17. A device as claimed in claim 1, wherein said pharmaceutically active agent in encapsulated in liposomes.
- 18. A device as claimed in claim 1, wherein said pharmaceutically active agent is modified so as to be resistant to attack by proteolytic enzymes.
- 19. A device as claimed in claim 1, wherein said pharmaceutically active agent is selected from a group consisting of vasopressin, human growth hormone, insulin, interferon, erythropoietin and calcitonin.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9409281 |
May 1994 |
GB |
|
RELATIONSHIP TO OTHER APPLICATIONS
Applicant makes cross-reference to his presently pending U.S. patent application Ser. No. 08/350,488 (filed Dec. 6, 1994) entitled TRANSDERMAL PERFUSION OF FLUIDS, and to his re-examined U.S. Pat. No. B1 5,441,490 (re-examination certificate issued Sep. 16, 1997), entitled TRANSDERMAL PERFUSION OF FLUIDS, and to the application for said patent, U.S. patent application Ser. No. 84,267 (filed Jan. 7, 1992, PCT).
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/EP95/01726 |
|
WO |
00 |
11/8/1996 |
11/8/1996 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO95/30410 |
11/16/1995 |
WO |
A |
US Referenced Citations (4)
Foreign Referenced Citations (10)
Number |
Date |
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2097163 |
Dec 1993 |
CA |
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EP |
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EP |
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GB |
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JP |
90-187075 |
Jul 1990 |
JP |
90-204997 |
Aug 1990 |
JP |
90-340794 |
Nov 1990 |
JP |
9103271 |
Aug 1990 |
WO |
9211879 |
Jan 1992 |
WO |
Non-Patent Literature Citations (3)
Entry |
Morimoto, K., et al., “Effects of Proteolytic Enzyme-Inhibitors as an Absorption Enhancer on the Nasal and Transdermal Delivery Systems of Polypeptides,” J. Pharmacobio-Dyn., 14:34 (1991). |
Verhoef, J.C., et al., “Transport of Peptide and Protein Drugs Across Biological Membranes,” European Journal of Drug Metabolism and Pharmacokinetics, 15(2):83-93 (1990). |
Jacobsson, S., et al., “A New Principle for the Cleansing of Infected Wounds,” Scand. J. Plast Reconstr. Surg., 10:65-72 (1976). |