CA2116123A1 - Pressure-sensitive poly(n-vinyl lactam) adhesive composition and method for producing and using same - Google Patents
Pressure-sensitive poly(n-vinyl lactam) adhesive composition and method for producing and using sameInfo
- Publication number
- CA2116123A1 CA2116123A1 CA002116123A CA2116123A CA2116123A1 CA 2116123 A1 CA2116123 A1 CA 2116123A1 CA 002116123 A CA002116123 A CA 002116123A CA 2116123 A CA2116123 A CA 2116123A CA 2116123 A1 CA2116123 A1 CA 2116123A1
- Authority
- CA
- Canada
- Prior art keywords
- poly
- vinyl lactam
- composition
- radiation
- adhesive
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229920002554 vinyl polymer Polymers 0.000 title claims abstract description 83
- 239000000203 mixture Substances 0.000 title claims abstract description 76
- 230000001070 adhesive effect Effects 0.000 title claims abstract description 47
- 239000000853 adhesive Substances 0.000 title claims abstract description 46
- 238000004519 manufacturing process Methods 0.000 title description 4
- 239000007787 solid Substances 0.000 claims abstract description 27
- 239000004014 plasticizer Substances 0.000 claims abstract description 22
- 230000005865 ionizing radiation Effects 0.000 claims abstract description 19
- 238000002156 mixing Methods 0.000 claims abstract description 11
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims abstract description 8
- 230000001678 irradiating effect Effects 0.000 claims abstract 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 229910001868 water Inorganic materials 0.000 claims description 28
- 239000010410 layer Substances 0.000 claims description 26
- 230000005855 radiation Effects 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 18
- -1 poly(N-vinyl pyrrolidone) Polymers 0.000 claims description 17
- 230000001225 therapeutic effect Effects 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 12
- 239000012790 adhesive layer Substances 0.000 claims description 10
- 238000004891 communication Methods 0.000 claims description 10
- 239000004020 conductor Substances 0.000 claims description 9
- 229920001577 copolymer Polymers 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
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- 239000004599 antimicrobial Substances 0.000 claims description 6
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- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 239000003961 penetration enhancing agent Substances 0.000 claims description 3
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000002131 composite material Substances 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 239000007863 gel particle Substances 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- XHZPRMZZQOIPDS-UHFFFAOYSA-N 2-Methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(C)(C)NC(=O)C=C XHZPRMZZQOIPDS-UHFFFAOYSA-N 0.000 claims 1
- 238000005266 casting Methods 0.000 claims 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 31
- 229920000642 polymer Polymers 0.000 description 27
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 25
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 25
- 239000000463 material Substances 0.000 description 21
- 210000003491 skin Anatomy 0.000 description 16
- 235000011187 glycerol Nutrition 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000011248 coating agent Substances 0.000 description 11
- 238000000576 coating method Methods 0.000 description 11
- 238000004132 cross linking Methods 0.000 description 11
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- 239000003795 chemical substances by application Substances 0.000 description 10
- 239000000499 gel Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 9
- 238000003475 lamination Methods 0.000 description 8
- ZPOLOEWJWXZUSP-WAYWQWQTSA-N bis(prop-2-enyl) (z)-but-2-enedioate Chemical compound C=CCOC(=O)\C=C/C(=O)OCC=C ZPOLOEWJWXZUSP-WAYWQWQTSA-N 0.000 description 7
- 229920001519 homopolymer Polymers 0.000 description 7
- 229920001477 hydrophilic polymer Polymers 0.000 description 7
- 150000002500 ions Chemical class 0.000 description 7
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 150000003951 lactams Chemical class 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
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- 239000006227 byproduct Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 5
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- 239000000843 powder Substances 0.000 description 4
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- 238000012360 testing method Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
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- 239000011149 active material Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 230000002500 effect on skin Effects 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 150000005846 sugar alcohols Polymers 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 2
- GUTLYIVDDKVIGB-OUBTZVSYSA-N Cobalt-60 Chemical compound [60Co] GUTLYIVDDKVIGB-OUBTZVSYSA-N 0.000 description 2
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- 108060003955 Contactin Proteins 0.000 description 2
- 229920002274 Nalgene Polymers 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000012711 adhesive precursor Substances 0.000 description 2
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- 230000008901 benefit Effects 0.000 description 2
- 230000002844 continuous effect Effects 0.000 description 2
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- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
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- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
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- 238000002360 preparation method Methods 0.000 description 2
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- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
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- NKYXPUKJMFIOLB-UHFFFAOYSA-N 1-ethenyl-3-propylaziridin-2-one Chemical compound CCCC1N(C=C)C1=O NKYXPUKJMFIOLB-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
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- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
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- 210000000434 stratum corneum Anatomy 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/58—Adhesives
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09J—ADHESIVES; NON-MECHANICAL ASPECTS OF ADHESIVE PROCESSES IN GENERAL; ADHESIVE PROCESSES NOT PROVIDED FOR ELSEWHERE; USE OF MATERIALS AS ADHESIVES
- C09J139/00—Adhesives based on homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Adhesives based on derivatives of such polymers
- C09J139/04—Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01R—ELECTRICALLY-CONDUCTIVE CONNECTIONS; STRUCTURAL ASSOCIATIONS OF A PLURALITY OF MUTUALLY-INSULATED ELECTRICAL CONNECTING ELEMENTS; COUPLING DEVICES; CURRENT COLLECTORS
- H01R4/00—Electrically-conductive connections between two or more conductive members in direct contact, i.e. touching one another; Means for effecting or maintaining such contact; Electrically-conductive connections having two or more spaced connecting locations for conductors and using contact members penetrating insulation
- H01R4/04—Electrically-conductive connections between two or more conductive members in direct contact, i.e. touching one another; Means for effecting or maintaining such contact; Electrically-conductive connections having two or more spaced connecting locations for conductors and using contact members penetrating insulation using electrically conductive adhesives
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2666/00—Composition of polymers characterized by a further compound in the blend, being organic macromolecular compounds, natural resins, waxes or and bituminous materials, non-macromolecular organic substances, inorganic substances or characterized by their function in the composition
- C08L2666/02—Organic macromolecular compounds, natural resins, waxes or and bituminous materials
- C08L2666/14—Macromolecular compounds according to C08L59/00 - C08L87/00; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2666/00—Composition of polymers characterized by a further compound in the blend, being organic macromolecular compounds, natural resins, waxes or and bituminous materials, non-macromolecular organic substances, inorganic substances or characterized by their function in the composition
- C08L2666/28—Non-macromolecular organic substances
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01R—ELECTRICALLY-CONDUCTIVE CONNECTIONS; STRUCTURAL ASSOCIATIONS OF A PLURALITY OF MUTUALLY-INSULATED ELECTRICAL CONNECTING ELEMENTS; COUPLING DEVICES; CURRENT COLLECTORS
- H01R2201/00—Connectors or connections adapted for particular applications
- H01R2201/12—Connectors or connections adapted for particular applications for medicine and surgery
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S522/00—Synthetic resins or natural rubbers -- part of the class 520 series
- Y10S522/911—Specified treatment involving megarad or less
- Y10S522/912—Polymer derived from ethylenic monomers only
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S526/00—Synthetic resins or natural rubbers -- part of the class 520 series
- Y10S526/931—Pressure sensitive adhesive
Abstract
2116123 9310201 PCTABS00022 A hydrophilic, pressure-sensitive adhesive composition prepared by irradiating solid poly(N-vinyl lactam) with ionizing radiation to crosslink the poly(N-vinyl lactam) and thereafter mixing the radiation-crosslinked poly(N-vinyl lactam) with essentially unirradiated plasticizer in an amount sufficient to form a cohesive, pressure-sensitive adhesive composition. The composition is useful as a biomedical adhesive for transmitting or receiving electrical signals as a component (14) of a biomedical electrode (10).
Description
W~?~3t~ CT/US~2~09~7 21161~
PRESSURE-SENSITIVE POLY~N-VINYL LACTAM) ADHESIVE
COMPOSITIC)N AND METHOD FOR PRODUCING AND U~;ING SAME
Field of th~ Inv~ntion `
Thi~ invention relat~s to a hydrophilic prescure-sensitive adheQive composition formed from the mixture of a solid, :
radiation-cro~linked poly~N-vinyl lactam) and an e~sentially unLrradLated plasticizer. This invention also relate~ to a method ~or producing the compoQition by radiation-crosslin~ing solid poly~N-vinyl lactam) and mixing the radiation-cro~slinked poly(N-vinyl lactam) with a pla~ticizer to render a cohesi~e, swellable, and pre~ure-sensitive adhe~ive composition. ;--Backqround~Of t~L-lr~lELQ~
Many medical adhe~ives are known. Often, the~e adhe~ive~ are copolymers of hydrophobic water-in~oluble monomers such as i~ooctyl acrylate and a 3mall ~ount of a water-soluble monomer such as a ~hort chain a,~-un~at:urated carboxyllc acid or an N-~inyl lact~m. While these copolymer~ make excellent m~dical adhesive~, the pre~ence o~ substant$al amount~ of ionic or highly polax ~olvent~ re3ults in pha~e separat:ion.
Conductive adhe~ive~ have been known for many years.
One clas~ of conductive adhesives has employed homopolymers or copolymer~ of N-~inyl lactams such as N-vinyl~-pyrrolidone. U.S. ;~
Pat. Nos. 4,273,135 and 4,352,359 ~both Larimore et al.) di~clo~e -~
non-ionic water-sol~ble polymers prepared from N vinyl lactams.
However, no cro4slinking of such polymers i~ di~closed.
Crosslinking allows for higher amounts of a plasticizer for the ~-compo~ition without reducing cohe~ivene~ of the composition below -~
acceptable level~.
U.S. Pat. No~. 4,527,087~and 4,539,996 (both Engel) disclo~e the polym2rization of an un~aturated free-radically -~ ;
polymerizable m~terial which is ~oluble in a polyhydric alcohol, where the unsaturated material iB cro slinked with a multifunctional i -~0 unsaturated free-radically polymerizable~material. ~U~S. Pat~ No.
4,554,924 (E~gel) discloses a ~onductive adhesive formed by n e~entially ~olventle~s free~radical polymerization of an adhesive precursor having a polyhydric alcohol, at least one non-ionic ~-monomer, an initiator, a crosRlinker, and an ionizable salt present in amounts suf~icient to render the composition eIectrically conductive. One of the non-ionic free-radically polymerizable monomers can be N-vinyl pyrrolidone. The es3~ntially solventless ~; -precursor can be coated onto the electrode plate or transfer sheet ,-.~
'''.,;' ~-, o~ PCr/US~/()9397 and ~xpo~ed to ~ither heat or actinic radiation which form~ the ~l~ctrically cond~ctive preseure-s~nsitive adhe~ive. The precur~or may alao be ~xpo~ed to electron beam radiation to facilitat~ the cros~linking.
U.S. Pat. No. 4,848,353 (Engel~ disclo~e~ an slectrically-conductive, pre~sure-~ensitive adhesive composition of a homogeneous mi~ture of a copolymer matrix and a plasticizing, electrically conductive solution. The composition need not be covalently crosslinXed but a cros31inker may be used. The copolymer matrix i8 form~d from a free-radical polymeri~able adhesive precursor having at lea~t one water-soluble hydrogen bond donating monomer, at least one water~soluble hydrogen bond accepting monomer, and either a photo or thermal free radical initiator. N~vinyl -~
lactams may be ussd as the hydrogen bond accepting monomer with ~-lS vinyl pyrrolidone being preferred.
European Pat. Publication 0322098 (Duan) discloses a cro~linked hydrophilic polymer composition which i8 u~eful as a pre~sure-sen~itive adhesive. The composition comprise3 a cro~slinked, cohesive, ewellable polymeric matrix and a plasticizing solution. The croYslinked, cohe~ive, ~wellable polymeric matrix i~
formed from the free-radical polymerization of a precur~or having a monomeric ~pecies of N-vinyl lactam~ and a cro~slinker of a multi-ethylenlcally unsaturated compound whe~.ein the ethyle~ic groups are ~inyl, allyl, or methallyl groups bonded to nitrogen or oxygen atom~. The cros~linker and plasticizer are pre~ent in controlled amounts sufficient to render a pres~ure-sensiti~e adhesive swellable matrix.
A continuing concern for the preparation of hydrophilic polymers used as medical adhe~ive3 iB biocompatibility. Not only mus~ the pre sure-sensitive adhesive compo0ition adhere to mammalian ~kin, but also the adherence to mammalian skin must not cau~e ~kin irritation~ toxicity reaction, or other d~letPriou~ effects of contacting a pol~eric ~omposition to livin~ tissue. Composition~
which are prepared by the polymerization of monomers must proceed through exacting procedure3 to minimize the residual preBence of unreacted monomer~. When cro~linking agents are employed to chemically crosslink a pol~mer, ~uch cro~slinking agents can also leave re~idual~ and produce und~ired byproducts.
I Another ap~roach to preparing conductiYe adhe~ives involves irradiation cro~linking of uncro~slinked polymers in the pre~ence of plas~icizers. U.S. Pat. No~. 4,699,146 and 4,750,482 ~Sieverding) disclo~e a water-in~oluble, hydrophilic ela3tomeric, ; ;~
pres~ure ~snsitive adhe3iv~ that includ~s at lea~t on~ irradiation oros~linked synth~tic organic pol~m~r and ~n adhe~ive pla~ticizer. ~;~
The cro~slinked polymer iq formed by di~per~ing or ~olubilizing at `
lea~t on~ suitable gel-forming, uncroR~linked ~ynthe~ic organic
PRESSURE-SENSITIVE POLY~N-VINYL LACTAM) ADHESIVE
COMPOSITIC)N AND METHOD FOR PRODUCING AND U~;ING SAME
Field of th~ Inv~ntion `
Thi~ invention relat~s to a hydrophilic prescure-sensitive adheQive composition formed from the mixture of a solid, :
radiation-cro~linked poly~N-vinyl lactam) and an e~sentially unLrradLated plasticizer. This invention also relate~ to a method ~or producing the compoQition by radiation-crosslin~ing solid poly~N-vinyl lactam) and mixing the radiation-cro~slinked poly(N-vinyl lactam) with a pla~ticizer to render a cohesi~e, swellable, and pre~ure-sensitive adhe~ive composition. ;--Backqround~Of t~L-lr~lELQ~
Many medical adhe~ives are known. Often, the~e adhe~ive~ are copolymers of hydrophobic water-in~oluble monomers such as i~ooctyl acrylate and a 3mall ~ount of a water-soluble monomer such as a ~hort chain a,~-un~at:urated carboxyllc acid or an N-~inyl lact~m. While these copolymer~ make excellent m~dical adhesive~, the pre~ence o~ substant$al amount~ of ionic or highly polax ~olvent~ re3ults in pha~e separat:ion.
Conductive adhe~ive~ have been known for many years.
One clas~ of conductive adhesives has employed homopolymers or copolymer~ of N-~inyl lactams such as N-vinyl~-pyrrolidone. U.S. ;~
Pat. Nos. 4,273,135 and 4,352,359 ~both Larimore et al.) di~clo~e -~
non-ionic water-sol~ble polymers prepared from N vinyl lactams.
However, no cro4slinking of such polymers i~ di~closed.
Crosslinking allows for higher amounts of a plasticizer for the ~-compo~ition without reducing cohe~ivene~ of the composition below -~
acceptable level~.
U.S. Pat. No~. 4,527,087~and 4,539,996 (both Engel) disclo~e the polym2rization of an un~aturated free-radically -~ ;
polymerizable m~terial which is ~oluble in a polyhydric alcohol, where the unsaturated material iB cro slinked with a multifunctional i -~0 unsaturated free-radically polymerizable~material. ~U~S. Pat~ No.
4,554,924 (E~gel) discloses a ~onductive adhesive formed by n e~entially ~olventle~s free~radical polymerization of an adhesive precursor having a polyhydric alcohol, at least one non-ionic ~-monomer, an initiator, a crosRlinker, and an ionizable salt present in amounts suf~icient to render the composition eIectrically conductive. One of the non-ionic free-radically polymerizable monomers can be N-vinyl pyrrolidone. The es3~ntially solventless ~; -precursor can be coated onto the electrode plate or transfer sheet ,-.~
'''.,;' ~-, o~ PCr/US~/()9397 and ~xpo~ed to ~ither heat or actinic radiation which form~ the ~l~ctrically cond~ctive preseure-s~nsitive adhe~ive. The precur~or may alao be ~xpo~ed to electron beam radiation to facilitat~ the cros~linking.
U.S. Pat. No. 4,848,353 (Engel~ disclo~e~ an slectrically-conductive, pre~sure-~ensitive adhesive composition of a homogeneous mi~ture of a copolymer matrix and a plasticizing, electrically conductive solution. The composition need not be covalently crosslinXed but a cros31inker may be used. The copolymer matrix i8 form~d from a free-radical polymeri~able adhesive precursor having at lea~t one water-soluble hydrogen bond donating monomer, at least one water~soluble hydrogen bond accepting monomer, and either a photo or thermal free radical initiator. N~vinyl -~
lactams may be ussd as the hydrogen bond accepting monomer with ~-lS vinyl pyrrolidone being preferred.
European Pat. Publication 0322098 (Duan) discloses a cro~linked hydrophilic polymer composition which i8 u~eful as a pre~sure-sen~itive adhesive. The composition comprise3 a cro~slinked, cohesive, ewellable polymeric matrix and a plasticizing solution. The croYslinked, cohe~ive, ~wellable polymeric matrix i~
formed from the free-radical polymerization of a precur~or having a monomeric ~pecies of N-vinyl lactam~ and a cro~slinker of a multi-ethylenlcally unsaturated compound whe~.ein the ethyle~ic groups are ~inyl, allyl, or methallyl groups bonded to nitrogen or oxygen atom~. The cros~linker and plasticizer are pre~ent in controlled amounts sufficient to render a pres~ure-sensiti~e adhesive swellable matrix.
A continuing concern for the preparation of hydrophilic polymers used as medical adhe~ive3 iB biocompatibility. Not only mus~ the pre sure-sensitive adhesive compo0ition adhere to mammalian ~kin, but also the adherence to mammalian skin must not cau~e ~kin irritation~ toxicity reaction, or other d~letPriou~ effects of contacting a pol~eric ~omposition to livin~ tissue. Composition~
which are prepared by the polymerization of monomers must proceed through exacting procedure3 to minimize the residual preBence of unreacted monomer~. When cro~linking agents are employed to chemically crosslink a pol~mer, ~uch cro~slinking agents can also leave re~idual~ and produce und~ired byproducts.
I Another ap~roach to preparing conductiYe adhe~ives involves irradiation cro~linking of uncro~slinked polymers in the pre~ence of plas~icizers. U.S. Pat. No~. 4,699,146 and 4,750,482 ~Sieverding) disclo~e a water-in~oluble, hydrophilic ela3tomeric, ; ;~
pres~ure ~snsitive adhe3iv~ that includ~s at lea~t on~ irradiation oros~linked synth~tic organic pol~m~r and ~n adhe~ive pla~ticizer. ~;~
The cro~slinked polymer iq formed by di~per~ing or ~olubilizing at `
lea~t on~ suitable gel-forming, uncroR~linked ~ynthe~ic organic
-2~
,,','-':
w~ o~ 2 1 1 6 ~ 2 ~ P~T/US92/0~3~97 polym~r in a pl~ticl~er that ha~ a compo~ition the same a~ or di~fQr~nt than the adhesi~e pla~ticizer, and then ubje~ting the re~ulting solution or dispersion to an appropriate dosage of irradiation. One example of an uncr~sslinked ~ynthetic organic polymer includes repeating units derived from an N-vinyl lactam monomer which i~ preferred amon~ monomeric candidate~. The aolubilizing plasticizer include~ at least one substantially non~
volatile elasticizer and conveniently includes a volatile solvent which can be aqueou~, nonaqueou~, or a mixture. Preferably the 1~ volatile solvent i~ water. The ~ub~tantially non-volatile ela~ticizer can be a polyhydric alcohol, a lactam, a glycol, among o~her~ listed. But it is neces~ary that the elasticizer prQsent during the irradiation treatment ~tep be irradiation cros~linkin~
compatible. Glycerin tend~ to reduce effectivenes3 of irradiation crosslinking and should not be pre~ent prior to irradiation treatment in an amount greater than about 5% of the total formula weight. Glycerin can be added once cro~slinking has been completed.
~owever, ionizing radiation o~ a pla~ticizing liquid can produce small molecule contaminants and other byproducts when ionizing cro~linking iq performed on polymer~ in the presence of other ~aterials. Further, adhe~ive gel~ containing level~ of pLa~ticizing glycerin greater khan about 5~ of the total formula w~i~ht cannot be directly prepared Eince glycerin cuntaining pr~cursor solution~ do not cro~slink upon expo~ure to ionizing radiation. Thus, these Sieverding patent~ teach a cumber~ome proce3q of plasticizing an ionizing radiation ~ro~linked polymer. ~ -Other U.S. patents ha~e alno di~clo~ed the irradiation -of poly(N-~inyl lactam) in the presence of other material~. U.S.
Pat. No. 4,089,832 ~Yamauchi et al.) disclo~es th~ crosslinking of -~
polyvinyl pyrrolidone while in aqueou~ solution followed by pul~erizing the cro~linked product and mixing with a plastic ~ub~tance selected from thermoplastic or thermohardenable pla~tic~
U.S. Pat. No. 3,900,378 (Yen et al.3 di~clo~es a particulate polymer u3eful a~ a 80il a~endment prepared by blending a mixture of a hydrophilic polymer, a pulverulent inert filler, and water prior ~o expo~ing the mixture to ionizing radiation for a period of time to cro~slink the polymer.
U.S. Pat. No. 4,646,730 (Schonfeld et al.) di~closes an aqueou~ di~per~ion of pol~vinyl pyrrolidone, silYer ~ulfadiazine, magneQium tri~ilicate and water, followed by expo~ure tQ E-Beam ;-radia~ion to provide a hydrogel product having a uniform deep yellow color retained over a long shelf life.
U.S. Pat~ No. 4,9~9,6U7 (~usch et al.) disclo~e3 hydrophilic gels which are non tringy and highly conduct~ve~
prepared from an aqueou~ mixture of poly(vinylpyxrolidone) a
,,','-':
w~ o~ 2 1 1 6 ~ 2 ~ P~T/US92/0~3~97 polym~r in a pl~ticl~er that ha~ a compo~ition the same a~ or di~fQr~nt than the adhesi~e pla~ticizer, and then ubje~ting the re~ulting solution or dispersion to an appropriate dosage of irradiation. One example of an uncr~sslinked ~ynthetic organic polymer includes repeating units derived from an N-vinyl lactam monomer which i~ preferred amon~ monomeric candidate~. The aolubilizing plasticizer include~ at least one substantially non~
volatile elasticizer and conveniently includes a volatile solvent which can be aqueou~, nonaqueou~, or a mixture. Preferably the 1~ volatile solvent i~ water. The ~ub~tantially non-volatile ela~ticizer can be a polyhydric alcohol, a lactam, a glycol, among o~her~ listed. But it is neces~ary that the elasticizer prQsent during the irradiation treatment ~tep be irradiation cros~linkin~
compatible. Glycerin tend~ to reduce effectivenes3 of irradiation crosslinking and should not be pre~ent prior to irradiation treatment in an amount greater than about 5% of the total formula weight. Glycerin can be added once cro~slinking has been completed.
~owever, ionizing radiation o~ a pla~ticizing liquid can produce small molecule contaminants and other byproducts when ionizing cro~linking iq performed on polymer~ in the presence of other ~aterials. Further, adhe~ive gel~ containing level~ of pLa~ticizing glycerin greater khan about 5~ of the total formula w~i~ht cannot be directly prepared Eince glycerin cuntaining pr~cursor solution~ do not cro~slink upon expo~ure to ionizing radiation. Thus, these Sieverding patent~ teach a cumber~ome proce3q of plasticizing an ionizing radiation ~ro~linked polymer. ~ -Other U.S. patents ha~e alno di~clo~ed the irradiation -of poly(N-~inyl lactam) in the presence of other material~. U.S.
Pat. No. 4,089,832 ~Yamauchi et al.) disclo~es th~ crosslinking of -~
polyvinyl pyrrolidone while in aqueou~ solution followed by pul~erizing the cro~linked product and mixing with a plastic ~ub~tance selected from thermoplastic or thermohardenable pla~tic~
U.S. Pat. No. 3,900,378 (Yen et al.3 di~clo~es a particulate polymer u3eful a~ a 80il a~endment prepared by blending a mixture of a hydrophilic polymer, a pulverulent inert filler, and water prior ~o expo~ing the mixture to ionizing radiation for a period of time to cro~slink the polymer.
U.S. Pat. No. 4,646,730 (Schonfeld et al.) di~closes an aqueou~ di~per~ion of pol~vinyl pyrrolidone, silYer ~ulfadiazine, magneQium tri~ilicate and water, followed by expo~ure tQ E-Beam ;-radia~ion to provide a hydrogel product having a uniform deep yellow color retained over a long shelf life.
U.S. Pat~ No. 4,9~9,6U7 (~usch et al.) disclo~e3 hydrophilic gels which are non tringy and highly conduct~ve~
prepared from an aqueou~ mixture of poly(vinylpyxrolidone) a
-3~
WC~ ln~01 PCI`/US92/0~397 2~ ;123 vi~co~ity-enhancing hydrophilic polymer, and an electrolyte to provide a uniform cohesive aqueou~ mi~ture ~ubstantially free of unbound water. The aqueou~ mixture i~ applied or ca~t to a de~ired thickness and subjected to cro~lin~ing high energy irradiation to initiate or precipitate the crosslinking polymer chain~.
European Pat. Publication 0 107 376 ~Thomp~on et al.) disclo~es a gel dres~ing made from poly~vinylpyrrolidone) having a high molecular weight by dis~olving the polymer in water and crosslinking the polymer with ionizing radiation for tLme ~ufficient to change the viaco~ity of the solution.
U.S. Pat. No. 4,792,400 (Dougherty et al.) disclo~ea preparation of a particulate, normally solid, water-insol~ble vinyl lactam polymer containing between about 0.5 and about 10% of non-cro~slinked and/or unaaturated ~ite~ on the high molecular weight polymer chains. These polymers have an average particle size sufficient to be retained on a filtering means. The water-insoluble polymer i8 ~ubje~ted to irradiation with radiant ensrgy at a do~age level of between about 0.001 and about 20 megarads. The polymeric materiala can be irr~diated in a dry ~tate or as a liquid ~lurry.
U~S. Pat. No. 4,904,247 (Therriault et al.) di~clo~ea a ~
pre~aure-s2nsitive hydrophilic laminate compo~ite comprising layer~ -of a tacky pressure-a2nsitive adhe~ive hydrophilic polymer blend and a non~tacky hydrophilic polymer blend. The blend~ are prefe~ably comprised of homopol~mers or aopolymerEI of N-vinyl lactam, a ralatively hydrophobic water-insoluble acrylate polymer and wat~r soluble plasti~i~er. The blends have a micropha~ ~eparated morphology. Pr~s~ure-~ensitive adhesivene~s i8 determined by the amount of N-vinyl lactam polymer and the amount of pla~tici~er in the blend~
summary of the Invention Unexpectedly, ~uperior hydrophilic, medically u~eful, pre~ure-sen~itive adheaive com~o~ition are prepared by a proce~
~ which both a~oid~ re~idual monom~r~ and by-product~ of chemical cros~linking and al~o avoids by-product~ of irradiated plasticizer and other additive~.
A hydrophilic, pressure-~es itive adhe~ive composition of the pre~ent invention compri~es a ~olid, radi~tion-cro~linked ! poly(N-vinyl lactam) and an e~entially unirradia~ed pla~tiicizer~
pre~ent in an amount sufficient to form a cohesi~e, pres~ure-~an~itive adhe3ive compo0ition.
A hydrophilic, pre~ure-ten itive adhesive composition ~`~
of the pre~ent invention can b8 prepared by a meth~d compri~ ng (a~ -irradiating solid ~on-cro~linked poly~N-vinyl lactam) wi~h ionizing .,:,-.",!.", radiation to cros~link the p~ly(N-vinyl lactam) and (b~ mixing the radiation-crosslinked poly(N-vinyl lactam) with an e~3e~tially '~-"`'; '~'`' ,~; ~ ..
2 1 1 ~ 1 2 3 PCr/US9~/09397 unirradlated plaaticiz~r in an amoumt suf~icient for the compo~ition to be a cohe~ive, pressure-sensitive adhesive.
"Solid" mean~ that poly~vinyl lactam3 iB not required to be mixed wi~h any other material prior to irradiation to cro~slink such poly~vinyl lactam). No mixing with solvents, plasticizers or chemical cros~linking agents is required to prepare radiation-crosslinked poly(vinyl lactam) u~eful for the pre~ent invention. Commercially available non-cro~slinked poly(vinyl lactam) can be ~mployed in particulate form for irradiation to -cros~link such poly~vinyl }actam).
~Ess~ntially unirradiated" mean~ that plasticizer u~eful with solid, radiation-cro~slin~ed poly~N-vinyl lactam) i8 neither subjected to any irradiation during the crosslinking of ~uch solid poly~N-vinyl lactam~ nor i~ subjected to any irradiation at any other time at a do~age which would d~grade the pl~sticizer.
A hydrophilic, pres~ure-Yensitive adhesive c4mposition of the pre~3nt: invention can be used as a conductive adhesi~re component of a biomedical electrode, a~ a mammalian ~kin-contacting adhesive layer in a medical tape, or as an adhesi~re in a mammalian skin pharmaceutical delivery device.
It i~ a feature of the invention that it i8 pos~ible to prepare hydrophilic pre~sure-~ensiti~re adhesive compo~itions by ~ubjecting poly~N-vinyl lactam~ exist:ing in a solid form to cro~linking with ionizing radiation It i~ another feature of the invention that any plasticizer needed to render radiation-cros~linked poly(N-vinyl lactam) a coheRive, pre~ure-~ensitive adh~sive can b~ added after the poly(N-vinyl lactam) ha~ been radiation-cro~slinked.
It i~ another feature of th~ invention that biocompatible and/or therapeutic and/or ionically-conductive materials can be added to the es~entially unirradiated plasticiz~r `~
or to the plasticized compo~ition, eliminating the po~ibility of expoBure of the biocompatible an~/or therapeutic and/or ionically- ~
conductive material~ to deleteriou~ effect~ of ionizin~ radiation ~ ~-otherwise admini~t~red in do~ages suficient to cro~slink the hydrophilic polymer. ~;
It i3 another feature of the pre~ent invention thaS `~
biocompatible andjor therapeut:Lc and/or ionically-conductive material~ added tQ the pre~sure~sensitive adhesive compQ~ition facilitate u~e a~ biomedical electrode~, pharmaceutic~l delivery ;~
device~, or mammalian ~kin coverin~
It i~ an advantage of the invention that the pres~ure~
~en~itive adheQive compo~ition~ prepared by proce~ss of the pre~ent invention minimi~e the pre~ence of radiation-degraded pla~ticiz~r, ~ .
radiation-de~rad~d biocompatible and~or therapeutic and/or ;~
ionically~conductiYe material~, residual monomer~ or cro~slinking -5- ` . ~
~,,``,.~.:
'~.''.'~ ' ~ 1n201 PC~/US~2/0~397 agent~, or other byproducts of reaction or crosslinking of a polymt in the pre~ence of other mate~ial~.
It i~ another advantage of the in~ention that plasticizing of radiation-crosslinked poly(N-vinyl lactam) can include glycerin added after radiation-cros~linking ha~ been completed.
Di~cussion of embodiments of the invention follows.
Brief De~criDtion of the ~rawinq FIG. 1 is a top plan vi~w of a biomedical electrode containing hydrophili~ pr~s3ure-sensitive adhesive of the present invention.
FIG. 2 is an exploded sectional view of the biomedical electrode of FIG. 1.
FIG. 3 is a ectional view of a medical mammalian ~kin covering conta~ming hydrophilic, pre~ure-sensitive adhe~ive of the pre~ent invention.
FIG. 4 ~ a sectional vi~w of a pharmaceutical delivery device containing hydrophilic, presaure-sensitive adhesive o~ the ::
pre~nt invention.
FIG. 5 i~ a graph comparing swelling capacity to the mole fraction o~ chemical crosslinker for comparative examples 34- .40 .
~5 . mbodiment~ of the Invention Hvdrophilic, Pre~ure-Sen3itive Adhesive Composition A hydrophilic, pressure-sensitive adhe~ive compo~ition - :
of the present invention compri~e~ a swellable, polylN-vinyl lactam~
radiation-crosslink~d while in a solid form and an e~entially unirradiated plasticizer pre~ent in an amount ~ufficient to form a , cohe~ive, pre~ure-~en~itivs adhe~ composition. The amount of pla~ticizer to be mixed with the radiation~crosslinked swellable ;:
poly~N-vinyl lactam) can range from about~50 to about 90 weight ~;
percent of th~ composition~ Con~equently, ~xclu~ive of any bio~ompatible andlor therapeutic and/or ionically-conducti~s ~ materials to be added to the compo~ition, the weight p~rcent o~ thé ~.
solid, radiatLon-cro~li.nked, ~wellable poly~N-vinyl lactam) can be from about 10 to about 50 weight perc~nt. When the poly(N-vinyl lactam) i8 poly(N-vinyl pyrrolidone~, the weight percent of poly~N- ~:
vinyl pyxrolidone~ can range from about 15 to about 45 percent and preferably from about 20 percent to about 40 percent. ~ :~
--6 ~
'""' ' W~ )t~)l 2 1 1 ~ 1 2 ~ PC~IVS~2/(~3~7 Pol~lN-~v1n~1 1 ctam) in a~Solid Po~m Poly~N-vinyl lactam) u~e~ul in the pr~ent invention can be in any form of solid ~u~ceptible to being radiation-cro~slinked.
Nonlimiting sxample~ of ~olid forme include particle~, pellet~, ~heet~, flakes, and ~ulk objects of various ~hape~, and coated obj~cts of variou~ ~hapes. Pr~ferably, poly(N-vinyl lactam) ~8 in the form of particles of a size le~s than about 1 cm, de~irably from about 0.1 ym to 250 ~m and preferably from about 10 ~m to about 75 ~m.
Poly(N-vinyl lactam) in a solid form can be a noncro~linked homopolymer or a noncro~lin~ed copolymer containing N-vinyl lactam monomeric unitB, which after irradiation i~ Rwellable in a plasticizer biocompatible wi~h mammalian ~kin. Preferably, noncros~linked homopolymer or noncros~linked copolymer i~ soluble in pla~ticiz~r biocompatible with mæmmalian ~kin in the ab~enc~ of radiation cro~31inking. N-vinyl lactam monomeric unit~ compri~e a majority of total monomeric unit~ o~ th~ polymer.
Nonlimiting examples of N-~nyl lactam monomers ar~ N-vinyl-2-pyrrolidone; N-vinyl-2-valerolactam; N-vinyl-2-caprolactam;
and mixtureR of any of the foregoing. Pre~erably, the N-vinyl lactam is N-vinyl-2-pyrrolidone. Preferably, the poly(N-vinyl actam) i~ a homopolymer of N-vinyl-2-pyrrolidone.
Nonlimiting example~ of non-N-vinyl lactam comonomer~
u~eful with N-vinyl lactam monomeric unit~ include N,N-dimethylacrylamide, acrylic acid, methiacrylic acid, hydroxy~thylmethacrylate, acrylamide, 2-acrylamido-2-methyi-1-propane sulfonic acid or its ~alt, and vinyl ~;~
acetat~.
The N-vinyl lactam monom~ric units comprise no le~ than about 50 weight percent of the monomeric unit~ pre3ent in th~
poly~N-~inyl lactam) in solid state form. ~ore preferably, the N-vinyl lactam monomeric units comprise 70 to 100 percent by weight of the poly~N-vinyl lactam) and mo~t preferably 90 to 100 percent by , weight of the poly(N~vinyl lact ~).
Noncro~slinked N-vinyl la~tam homopolymer and N-vinyl pyrrolidone/vinyl aceta e copolymers are commercially available. ~;
Nonlimlting sources of co~mercially available poly(N-Yin pyrrolidone) uYeful for the pr~a~nt inve~tion includ~ ~ldrich ~ Chemical Co. of Milwaukee, WI, 8ASF of Pa~sippany, NJ, ISP (G~F) of ~ ~Wayne, NJ, Dan River Corporation of Danville, VA~ and Spectrum ~;
Chemical ~anufactuxins~Corporation of Gardena, CA.
Poly(N~vinyl lactam) can have a Fikentscher R-value o at lea~t K-15 and preferably at lea~t ~-60~ and mo8t preferably at least K-90. ~ikent~cher K-value~ are de~cribed in ~lyneaux, ~ ;
~ater-Solubl~ Polymer~: Propertie~ and Behavior, Vol~ 1, CRC Pre~
lg83, pp. 151-152.
~ ,. . .
WO '93J I n~o I PCT/US92/(~931~7 ~ etQ~ 0xp~ur~ to ionizin~a radiation, poly~N-vinyl lactam) can hav~ a Swelling Capacity of at lsa~t abou~ 15 in water, preferably at least about 30 in water, and mo~t prefarably at least about 40 in water. ~wslling Capacity, S, i~ a mea~urement of the milliliters of water sorbed per gram of solid, radiation-cro~slinked poly~N-vinyl lactam), approximated by eguation I:
[ (PYP WT + H O WT ) X GEL ~3IGHT ~ _ p~p ~ ~ I .
PYP WT. '' ' where PVP wt. is polymer compo~ition weight, H20 wt. i9 water weight, Gel Height i~ height of ~wollen P~P in a vial, and Total Height i~ total height of material in the vial.
Swelling capacity correlates to a measurement of polym~r ~welling as a function of chemical cros~linking units in poly~N-vinyl lactam), acccrding to the equation II-S = C(~1/3 _ ~ 1/3) II
wher~ S i~ a measurement oE water ~orbed per gram of polymer, C i~ a constant characteri~tic of the polymer, i.e., the volume of water ~orbed per gram o~ polymer~ ~ is the averase number of backbone carbon atom~ in the pol~ner s~gment3 between crosslinke~ ;
junction~, and ~0 i~ the average number of backbone carbon atoms betw~en cro~linXed ~unctions when S $~3 zero. Swelling capacity and this equa~ion are di~cusaed in Errede, ~Molecular Interpretations of Sorption in Polymers Part I", Advan~e!3 in_Polymer Science Vol. 99, Springer-Verlag, Berlin Heidelberg Ge~nany ~pp. 21-36, 1991).
~:
Pla~t cizer ~ -Hydrophilic, pres~ure-~en~itiYe adhesive compositions of the pre~ent invention contain a plasticizer for the ~olid, radia~ion-cro~linked polylN-vinyl lactam). The pla~ticizer can be any plaBticiz~r which can ~well solid, radiation-cro~glinked poly~M-vinyl lactam) and which is bincompatible with mammalian skin.
Nonlimitin~ exampleo of pla~ticizer~ useful to swell the poly~N-vinyl lactam) in lude monohydric alcohols ~e.g~, ethanol and i~opropanol~, p~lyhydric alcohols, ~e.~., ethylene glycol, propylene glycol, polyethyl~ne glycol tMolecul~r W~ight between 200 and 600) and glycerin~, ether alcohol~ (0.g.~ glycol ether~)r other polyol ~- -plasticizer~ which do not cau~e mammalian ~kin irritation or toxic ;~
reaction, and water~
Dep~nding on the ultimate u~e desired for the ydrophillc preB~Ure-~e~itiVe adhe~ive composition, a mixture of a essentially non-v~latile plast~oizer and a volatile pla~ticiæer can be used, such as a mixture of non~volatile pla~icizer, (e.g., ~ --8~
~: . . ~, . ..
W~ 21 16123 ~ 9~ 397 ~lycq~ln or poly~thyl~ne glycol~ with water. Alternatively, only a non-volatile pla~ticizer ~uch as glycQrin or polyethylsne glycol, or only a volatile plasticizer such a~ water, can be u~ed to render a cohe~ive, pre~ure-~en~itiv~ adhe~ive composition.
For this in~rention, "e~sentially non-volatile" mean~
that a pla~ticizer a~ u~ed in the preaent invention will render ~olid, radiation-croAslinked poly(~-vinyl lactam) sufficiently cohesive and pressure-sen3itive adhesive, such that less than ten percent ~10~) of a given volume of plasticiz~r evaporates after ~xpo~ure to proc~sing condition~ or to storage condition~.
The pla~ticizer can be added in an ~mount ran~ing from about 50 to about 90 weight percent o~ the adhesive composition and pre~erably from about 60 to about 80 ~eight ~arcent. Of es~entially non-volatile pla~ticizers, glycerin and poly2thyl~ane glycol are preferred, with polyethylene glycol most preferred. Glycerin can compri~e up to 100 weig~t percent of the plasticizer. Polyethylene ~lycol can compri~e up to 100 weight p~arcent of the pla~ticizer.
Polyethylene glycol of either 300 molecular weight or 400 molecular weight is preferred with 300 molecular weight more preferred.
When the adhesive composition~ are used a~ an electrically conductive component of biomedical electrode~, the pla~ticizer can al~o opticnally includ~a water to improve ionic conductivity in the compo~ition and can include either glycerin or polyethylene glycol. In thi~ in~tance, water i3 u~ed as a pla~ticizer comprising from about 20 ~3rce~t to about 100 percent and preferably at least about 30 per~el~t by weight of the plaQticizer used.
Bioco~patible and/or Therapeutic and/or~Ionically- C nductive ~dditives Depending upon the u~e of the hydrophilic, pre~ure-~ensitive adhesive compo~ition of the present inv2ntion, variou~
biocompatible and~or therapeutic and/or ionically conductive ~-material~ can ~e included in the compo~ition~
For example, composition3 of the present invention can be u0ed as conductive adhesive in a ~iomedical electrode with the addition of an ionically conductive elçctrolyte to the compo~ition -~
after radiation-cro~slinking of the ~olid poly(N vinyl lactam) with ionizing radiation without deleteriously affecting the el~ctrolyte or the resulting compo~itionO Nonlimiting examples of electrolyte include ionic salts dissolved in the composition to provide ionic conductivity and can include lithi~m chloride, lithium perchlorate, ~odium citrate, and preferably pot~aium chloride. Alternatively, a redox couple such as a mixture of ferric and ferrou~ salt3 such a~
sulfate~ and giuconate3 can be added.
_g~
WO ~5J1()201 PCT/USg~/lJ~3g7 ~ IL 161~ 3 ~he ~mount~ of the~e ionic ~altB pre~ent in compo~itior, of the pre~ent invention ~re relatively ~mall, from about 0.5 to 5 percent ~y wei~h~ of the composition, and preferably about 2 to 3 weight percent. When a redox couple i~ used in compo~itions of th~
pre~ent invention, the biomedical electrode can recover from an overload potential. U.S. Pat. No. 4,846,185 ~Carim) di~close3 a redox couple totalling not more than about 20 percent by weight of the adhesive compo~ition.
Hydrophilic, pres~ure-~en~itive adhesive compositions of the pre~ent lnvention can also be used in the delivery of pharmaceuticals to or through mammalian ~kin, ~uch as topical or tran~dermal drug delivery ~ystem~. The pharmaceutical or other active ingredient can be compounded with the adhesive compo~ition after poly(N-vinyl lactam~ has been radiation-crosslinked, minimizing any po~ible deleterious interaction of the pharmaceutical or active ingredient with ionizing radiation in do0age~ ~ufficient to crosslink poly~N-vinyl lactam~.
A type of therapeutic proc~dure both involving application of electrical current to skin of a patient and a pharmaceutical is iontophoresis, which deliver~ an iontophoretically active pharmaceutical to or through mammalian skin with aid o~ an electrical current.
The hydrophil~c, pre~sure-sen~itive adhesive composikion can al~o be u~ed in therapeutic mammalian skin coverings, ~uch as drassings, wound clo3ur~ materials, tapea, and the like.
Preferably, for mammalian ~kin covering u~es, other biologically active materials ~an be added to the compo~ition of the pre~ent invention after irradiation of polylN-vinyl lactam~ without deleteriously ~ffecting the biologically a~tive material. .
Nonlimiting example~ of ~uoh other biologically active materials include hroad spectrum antimicrobial agents where it is de~ired to -reduce bacteria lev~ls to minimize infection risk or treat the ePfects of infPction~ at the ~kin or 3kin opening~ of a mammalian , patient. Broad Bpectrum antimicrobial agent~ re di3clo~ed in ~.S.
pat. No. 4,310,5090 Nonlimiting example~ of other antimicrobial agent~ include parachloromQtaxylenol; triclo~an; chlorhexidine and it~ ~alts ~uch a~ chlorhexi~ine acetate a~d chlorhexidin~ gluoonate;
iodine; iodophor~; poly-N-vinyl pyrrolidone-iodophors; ~ilver oxide, ~ilver and its 8alt8~ antibiotic8 (e~g., neomycin, bacitxacin, and polymyxin B). Antimicrobial a~ents can be included in the compo3ition af~er radiation of poly~N-vinyl lactam~ in a weight from -about 0.01 percent to about 10 peroent by wei~ht of the total ~ ;
eompo~ition O~her biocompatible and/or therapeutic material~ can be added to the composition such as compounda to buffer ~he pH of the composition to provide a non-irritating pH for use with eenBitive -10~
W~ 2 ~1612 3 P~r/uss2/o~3~7 mammalian ~kin tin~ue or to otherwi~e maximize antimicrobial activity. Also, penetration enhancing agents or excipient~ can be added to the composition when the pharmaceutical or other active agent for topical or tran~dermal deli~ery ~o requires.
Irradiation Cros~llnkin~ of_Poly(N-Viny~_~s~8m~
Poly~N-vinyl lactam) in any ~olid form i~ ~ubjected to ionizing radiation from a high-energy source. Nonlimiting exiample~
of ionizing radiation include alpha, beta, gamma, electron-beiam, and x-ray radiation. 0~ the~e ~ources of ionizing radiation, electron-beam irradiation and gi~mma irradiation are pre~erred. Sources of electron-beiam radiation are commerc~ally available, includtng an Energy Sciences Inc. ~odel CB-150 Electrocurtain Electron Beam Proces~or. SOurCeB of qi~mm~ irradiation are commercially available from Akomic Energy of Canada, Inc. u~ing a cobalt-60 high-ener~y cource.
lonizing radiation dn~ages are mea~uxed in megarad~
(mRad) or kilogxay~ (kGy). Dose~ o~ ionizing radiiation can be administered in a ~ingle do~e of the d~sired level of ionizing radiation or in multiple do~e~ which accumulate to the desired level of ionizing radiation. The do~age o ionizing radiation ~umulatively can range rsm about 25 kGys to about 400 kGy~ and pxeerably from about 25 ~Gy~ to about 200 kGy~. Pref~rably, ionizing radlation can achieve the de~ired level of crosslinking of poly(~-vinyl lactam) when the cumulative do~age of ionizing radiation ~xceeds 100 kGys (10 mRad~.
Poly~N-vinyl lactam~ can be irr di~ted in a 801id form wlth ioni~ing radiation in a package or container where the temperature, atmosphere, and other reaotion parameter~ can be controlled.
Temperature can range from about -80C to about lQODC `~;~
and preferably from about 10C to ab~ut 35C.
The atmo~pher~ can be air or preferably an inert a~mo~phere ~uch a~ nitrogen.
3~ The line ~peed for electron-beam irradiation can be about 15 meters/minu~e.
The pressure in the container can be atmo~pheri~, ele~ated or depre~ed. Preferably it i9 atmospheric.
Depending upon the control of the irradiation i ~onditions, poly(N~vinyl l~ctam) can be irradiated in a batch ~r con~inuou~ proce~
:
ethod o~ P~reParl~q-~y~r~hL~llc~ Pre~ure=~ Sly~_~
ComPo~ition3 A m~thod of preparing a hydrophilic, pres~ure-sen~ikive ~ ;
adhe~ive composition of the present invention can employ a minimum ,.
--11-- ~ . ;
` ;~' wo ~ 2~1 PC~/lJS~/0~3~7 number of ~co10gica11y comp~tibl~ manufacturing step~. The solid, radlatlon-cro~lLnked poly~N-vinyl lactam) i~ mixed wi~h ~entially unirradiated pla~ticiz~ and any oth~r optional additive~ into a ~olvent which iB es~entially volatile at or above ambient temperature~, ~uch as water~ athanol, methanol, and i30propanol. A
quantity of the ~u~penQion of radiation-cros~linked poly(N-vinyl lactam)~ eseentially unirradiated plasticizer, and any optional additive~ in the volatile solvent is then cast onto a ~urface of a substrate, which can be an inert sub~trate such a~ a liner for ~torage before further proce~sing or a ~urface d~signed for ultimate use, auch ~ a mean~ for electrical communication havLng an electrically conductive surface for u~e a~ a biomedical electrode.
Then the volatile ~olvent i~ essentially evaporated by the applLcation of heat, microwave energy, infrared energy, convective air flow or the like, in order to form a cohesive, pressure-sensitive adhe~ive compo~ition on the ~ub~trate.
Typically, a drying oven heated to about 65C can be employed. A
product liner can optionally be larninated over the field of pr~nsure-~ensit:L~e adhesive composition to protect that field from contamination.
~ coating of cohesive, prel3sure-sen~itive adhe~ive compo~ition can be applied to a Qub3trate surface. Coating thickna~o~ can range from about 0.125 mm to about 1.25 mm and preferably ~rom about ~.75 mm to about 1 mm, to yield a~ter evaporation of Qolvent a coating thich~Q~s ranging from about 0.05 mm to about 0.38 r~n and preferably from about 0.18 mm to bout 0.25 mm. With thi~ extremely thin coati~g of a conductive and preferably adhesive composition, a low profile and conformable biomedical electrode can be made.
3n The method can be prepared in a batch proce~s or in a continuous line process. If prepared by a continuouQ proce~, the ~ ;
laminate of a liner, field of cohe~ive, pre~3ur~-sensitive adhe~ive ~ :
compo~ition~ and 3ubstrate can be wound on a roll for bulk packaging , and further pr*ce~ing or can be cut u~ing dies known to thoee ~kill~d in the art into individual unit~r ~uch a~ biomedical electrode~ or biomedical electrode ~ubassemblie~, for furth~r proce~sing. U.S. Pat. No. 4,795,516 (Strand) and U.S. Pat. No.
WC~ ln~01 PCI`/US92/0~397 2~ ;123 vi~co~ity-enhancing hydrophilic polymer, and an electrolyte to provide a uniform cohesive aqueou~ mi~ture ~ubstantially free of unbound water. The aqueou~ mixture i~ applied or ca~t to a de~ired thickness and subjected to cro~lin~ing high energy irradiation to initiate or precipitate the crosslinking polymer chain~.
European Pat. Publication 0 107 376 ~Thomp~on et al.) disclo~es a gel dres~ing made from poly~vinylpyrrolidone) having a high molecular weight by dis~olving the polymer in water and crosslinking the polymer with ionizing radiation for tLme ~ufficient to change the viaco~ity of the solution.
U.S. Pat. No. 4,792,400 (Dougherty et al.) disclo~ea preparation of a particulate, normally solid, water-insol~ble vinyl lactam polymer containing between about 0.5 and about 10% of non-cro~slinked and/or unaaturated ~ite~ on the high molecular weight polymer chains. These polymers have an average particle size sufficient to be retained on a filtering means. The water-insoluble polymer i8 ~ubje~ted to irradiation with radiant ensrgy at a do~age level of between about 0.001 and about 20 megarads. The polymeric materiala can be irr~diated in a dry ~tate or as a liquid ~lurry.
U~S. Pat. No. 4,904,247 (Therriault et al.) di~clo~ea a ~
pre~aure-s2nsitive hydrophilic laminate compo~ite comprising layer~ -of a tacky pressure-a2nsitive adhe~ive hydrophilic polymer blend and a non~tacky hydrophilic polymer blend. The blend~ are prefe~ably comprised of homopol~mers or aopolymerEI of N-vinyl lactam, a ralatively hydrophobic water-insoluble acrylate polymer and wat~r soluble plasti~i~er. The blends have a micropha~ ~eparated morphology. Pr~s~ure-~ensitive adhesivene~s i8 determined by the amount of N-vinyl lactam polymer and the amount of pla~tici~er in the blend~
summary of the Invention Unexpectedly, ~uperior hydrophilic, medically u~eful, pre~ure-sen~itive adheaive com~o~ition are prepared by a proce~
~ which both a~oid~ re~idual monom~r~ and by-product~ of chemical cros~linking and al~o avoids by-product~ of irradiated plasticizer and other additive~.
A hydrophilic, pressure-~es itive adhe~ive composition of the pre~ent invention compri~es a ~olid, radi~tion-cro~linked ! poly(N-vinyl lactam) and an e~entially unirradia~ed pla~tiicizer~
pre~ent in an amount sufficient to form a cohesi~e, pres~ure-~an~itive adhe3ive compo0ition.
A hydrophilic, pre~ure-ten itive adhesive composition ~`~
of the pre~ent invention can b8 prepared by a meth~d compri~ ng (a~ -irradiating solid ~on-cro~linked poly~N-vinyl lactam) wi~h ionizing .,:,-.",!.", radiation to cros~link the p~ly(N-vinyl lactam) and (b~ mixing the radiation-crosslinked poly(N-vinyl lactam) with an e~3e~tially '~-"`'; '~'`' ,~; ~ ..
2 1 1 ~ 1 2 3 PCr/US9~/09397 unirradlated plaaticiz~r in an amoumt suf~icient for the compo~ition to be a cohe~ive, pressure-sensitive adhesive.
"Solid" mean~ that poly~vinyl lactam3 iB not required to be mixed wi~h any other material prior to irradiation to cro~slink such poly~vinyl lactam). No mixing with solvents, plasticizers or chemical cros~linking agents is required to prepare radiation-crosslinked poly(vinyl lactam) u~eful for the pre~ent invention. Commercially available non-cro~slinked poly(vinyl lactam) can be ~mployed in particulate form for irradiation to -cros~link such poly~vinyl }actam).
~Ess~ntially unirradiated" mean~ that plasticizer u~eful with solid, radiation-cro~slin~ed poly~N-vinyl lactam) i8 neither subjected to any irradiation during the crosslinking of ~uch solid poly~N-vinyl lactam~ nor i~ subjected to any irradiation at any other time at a do~age which would d~grade the pl~sticizer.
A hydrophilic, pres~ure-Yensitive adhesive c4mposition of the pre~3nt: invention can be used as a conductive adhesi~re component of a biomedical electrode, a~ a mammalian ~kin-contacting adhesive layer in a medical tape, or as an adhesi~re in a mammalian skin pharmaceutical delivery device.
It i~ a feature of the invention that it i8 pos~ible to prepare hydrophilic pre~sure-~ensiti~re adhesive compo~itions by ~ubjecting poly~N-vinyl lactam~ exist:ing in a solid form to cro~linking with ionizing radiation It i~ another feature of the invention that any plasticizer needed to render radiation-cros~linked poly(N-vinyl lactam) a coheRive, pre~ure-~ensitive adh~sive can b~ added after the poly(N-vinyl lactam) ha~ been radiation-cro~slinked.
It i~ another feature of th~ invention that biocompatible and/or therapeutic and/or ionically-conductive materials can be added to the es~entially unirradiated plasticiz~r `~
or to the plasticized compo~ition, eliminating the po~ibility of expoBure of the biocompatible an~/or therapeutic and/or ionically- ~
conductive material~ to deleteriou~ effect~ of ionizin~ radiation ~ ~-otherwise admini~t~red in do~ages suficient to cro~slink the hydrophilic polymer. ~;
It i3 another feature of the pre~ent invention thaS `~
biocompatible andjor therapeut:Lc and/or ionically-conductive material~ added tQ the pre~sure~sensitive adhesive compQ~ition facilitate u~e a~ biomedical electrode~, pharmaceutic~l delivery ;~
device~, or mammalian ~kin coverin~
It i~ an advantage of the invention that the pres~ure~
~en~itive adheQive compo~ition~ prepared by proce~ss of the pre~ent invention minimi~e the pre~ence of radiation-degraded pla~ticiz~r, ~ .
radiation-de~rad~d biocompatible and~or therapeutic and/or ;~
ionically~conductiYe material~, residual monomer~ or cro~slinking -5- ` . ~
~,,``,.~.:
'~.''.'~ ' ~ 1n201 PC~/US~2/0~397 agent~, or other byproducts of reaction or crosslinking of a polymt in the pre~ence of other mate~ial~.
It i~ another advantage of the in~ention that plasticizing of radiation-crosslinked poly(N-vinyl lactam) can include glycerin added after radiation-cros~linking ha~ been completed.
Di~cussion of embodiments of the invention follows.
Brief De~criDtion of the ~rawinq FIG. 1 is a top plan vi~w of a biomedical electrode containing hydrophili~ pr~s3ure-sensitive adhesive of the present invention.
FIG. 2 is an exploded sectional view of the biomedical electrode of FIG. 1.
FIG. 3 is a ectional view of a medical mammalian ~kin covering conta~ming hydrophilic, pre~ure-sensitive adhe~ive of the pre~ent invention.
FIG. 4 ~ a sectional vi~w of a pharmaceutical delivery device containing hydrophilic, presaure-sensitive adhesive o~ the ::
pre~nt invention.
FIG. 5 i~ a graph comparing swelling capacity to the mole fraction o~ chemical crosslinker for comparative examples 34- .40 .
~5 . mbodiment~ of the Invention Hvdrophilic, Pre~ure-Sen3itive Adhesive Composition A hydrophilic, pressure-sensitive adhe~ive compo~ition - :
of the present invention compri~e~ a swellable, polylN-vinyl lactam~
radiation-crosslink~d while in a solid form and an e~entially unirradiated plasticizer pre~ent in an amount ~ufficient to form a , cohe~ive, pre~ure-~en~itivs adhe~ composition. The amount of pla~ticizer to be mixed with the radiation~crosslinked swellable ;:
poly~N-vinyl lactam) can range from about~50 to about 90 weight ~;
percent of th~ composition~ Con~equently, ~xclu~ive of any bio~ompatible andlor therapeutic and/or ionically-conducti~s ~ materials to be added to the compo~ition, the weight p~rcent o~ thé ~.
solid, radiatLon-cro~li.nked, ~wellable poly~N-vinyl lactam) can be from about 10 to about 50 weight perc~nt. When the poly(N-vinyl lactam) i8 poly(N-vinyl pyrrolidone~, the weight percent of poly~N- ~:
vinyl pyxrolidone~ can range from about 15 to about 45 percent and preferably from about 20 percent to about 40 percent. ~ :~
--6 ~
'""' ' W~ )t~)l 2 1 1 ~ 1 2 ~ PC~IVS~2/(~3~7 Pol~lN-~v1n~1 1 ctam) in a~Solid Po~m Poly~N-vinyl lactam) u~e~ul in the pr~ent invention can be in any form of solid ~u~ceptible to being radiation-cro~slinked.
Nonlimiting sxample~ of ~olid forme include particle~, pellet~, ~heet~, flakes, and ~ulk objects of various ~hape~, and coated obj~cts of variou~ ~hapes. Pr~ferably, poly(N-vinyl lactam) ~8 in the form of particles of a size le~s than about 1 cm, de~irably from about 0.1 ym to 250 ~m and preferably from about 10 ~m to about 75 ~m.
Poly(N-vinyl lactam) in a solid form can be a noncro~linked homopolymer or a noncro~lin~ed copolymer containing N-vinyl lactam monomeric unitB, which after irradiation i~ Rwellable in a plasticizer biocompatible wi~h mammalian ~kin. Preferably, noncros~linked homopolymer or noncros~linked copolymer i~ soluble in pla~ticiz~r biocompatible with mæmmalian ~kin in the ab~enc~ of radiation cro~31inking. N-vinyl lactam monomeric unit~ compri~e a majority of total monomeric unit~ o~ th~ polymer.
Nonlimiting examples of N-~nyl lactam monomers ar~ N-vinyl-2-pyrrolidone; N-vinyl-2-valerolactam; N-vinyl-2-caprolactam;
and mixtureR of any of the foregoing. Pre~erably, the N-vinyl lactam is N-vinyl-2-pyrrolidone. Preferably, the poly(N-vinyl actam) i~ a homopolymer of N-vinyl-2-pyrrolidone.
Nonlimiting example~ of non-N-vinyl lactam comonomer~
u~eful with N-vinyl lactam monomeric unit~ include N,N-dimethylacrylamide, acrylic acid, methiacrylic acid, hydroxy~thylmethacrylate, acrylamide, 2-acrylamido-2-methyi-1-propane sulfonic acid or its ~alt, and vinyl ~;~
acetat~.
The N-vinyl lactam monom~ric units comprise no le~ than about 50 weight percent of the monomeric unit~ pre3ent in th~
poly~N-~inyl lactam) in solid state form. ~ore preferably, the N-vinyl lactam monomeric units comprise 70 to 100 percent by weight of the poly~N-vinyl lactam) and mo~t preferably 90 to 100 percent by , weight of the poly(N~vinyl lact ~).
Noncro~slinked N-vinyl la~tam homopolymer and N-vinyl pyrrolidone/vinyl aceta e copolymers are commercially available. ~;
Nonlimlting sources of co~mercially available poly(N-Yin pyrrolidone) uYeful for the pr~a~nt inve~tion includ~ ~ldrich ~ Chemical Co. of Milwaukee, WI, 8ASF of Pa~sippany, NJ, ISP (G~F) of ~ ~Wayne, NJ, Dan River Corporation of Danville, VA~ and Spectrum ~;
Chemical ~anufactuxins~Corporation of Gardena, CA.
Poly(N~vinyl lactam) can have a Fikentscher R-value o at lea~t K-15 and preferably at lea~t ~-60~ and mo8t preferably at least K-90. ~ikent~cher K-value~ are de~cribed in ~lyneaux, ~ ;
~ater-Solubl~ Polymer~: Propertie~ and Behavior, Vol~ 1, CRC Pre~
lg83, pp. 151-152.
~ ,. . .
WO '93J I n~o I PCT/US92/(~931~7 ~ etQ~ 0xp~ur~ to ionizin~a radiation, poly~N-vinyl lactam) can hav~ a Swelling Capacity of at lsa~t abou~ 15 in water, preferably at least about 30 in water, and mo~t prefarably at least about 40 in water. ~wslling Capacity, S, i~ a mea~urement of the milliliters of water sorbed per gram of solid, radiation-cro~slinked poly~N-vinyl lactam), approximated by eguation I:
[ (PYP WT + H O WT ) X GEL ~3IGHT ~ _ p~p ~ ~ I .
PYP WT. '' ' where PVP wt. is polymer compo~ition weight, H20 wt. i9 water weight, Gel Height i~ height of ~wollen P~P in a vial, and Total Height i~ total height of material in the vial.
Swelling capacity correlates to a measurement of polym~r ~welling as a function of chemical cros~linking units in poly~N-vinyl lactam), acccrding to the equation II-S = C(~1/3 _ ~ 1/3) II
wher~ S i~ a measurement oE water ~orbed per gram of polymer, C i~ a constant characteri~tic of the polymer, i.e., the volume of water ~orbed per gram o~ polymer~ ~ is the averase number of backbone carbon atom~ in the pol~ner s~gment3 between crosslinke~ ;
junction~, and ~0 i~ the average number of backbone carbon atoms betw~en cro~linXed ~unctions when S $~3 zero. Swelling capacity and this equa~ion are di~cusaed in Errede, ~Molecular Interpretations of Sorption in Polymers Part I", Advan~e!3 in_Polymer Science Vol. 99, Springer-Verlag, Berlin Heidelberg Ge~nany ~pp. 21-36, 1991).
~:
Pla~t cizer ~ -Hydrophilic, pres~ure-~en~itiYe adhesive compositions of the pre~ent invention contain a plasticizer for the ~olid, radia~ion-cro~linked polylN-vinyl lactam). The pla~ticizer can be any plaBticiz~r which can ~well solid, radiation-cro~glinked poly~M-vinyl lactam) and which is bincompatible with mammalian skin.
Nonlimitin~ exampleo of pla~ticizer~ useful to swell the poly~N-vinyl lactam) in lude monohydric alcohols ~e.g~, ethanol and i~opropanol~, p~lyhydric alcohols, ~e.~., ethylene glycol, propylene glycol, polyethyl~ne glycol tMolecul~r W~ight between 200 and 600) and glycerin~, ether alcohol~ (0.g.~ glycol ether~)r other polyol ~- -plasticizer~ which do not cau~e mammalian ~kin irritation or toxic ;~
reaction, and water~
Dep~nding on the ultimate u~e desired for the ydrophillc preB~Ure-~e~itiVe adhe~ive composition, a mixture of a essentially non-v~latile plast~oizer and a volatile pla~ticiæer can be used, such as a mixture of non~volatile pla~icizer, (e.g., ~ --8~
~: . . ~, . ..
W~ 21 16123 ~ 9~ 397 ~lycq~ln or poly~thyl~ne glycol~ with water. Alternatively, only a non-volatile pla~ticizer ~uch as glycQrin or polyethylsne glycol, or only a volatile plasticizer such a~ water, can be u~ed to render a cohe~ive, pre~ure-~en~itiv~ adhe~ive composition.
For this in~rention, "e~sentially non-volatile" mean~
that a pla~ticizer a~ u~ed in the preaent invention will render ~olid, radiation-croAslinked poly(~-vinyl lactam) sufficiently cohesive and pressure-sen3itive adhesive, such that less than ten percent ~10~) of a given volume of plasticiz~r evaporates after ~xpo~ure to proc~sing condition~ or to storage condition~.
The pla~ticizer can be added in an ~mount ran~ing from about 50 to about 90 weight percent o~ the adhesive composition and pre~erably from about 60 to about 80 ~eight ~arcent. Of es~entially non-volatile pla~ticizers, glycerin and poly2thyl~ane glycol are preferred, with polyethylene glycol most preferred. Glycerin can compri~e up to 100 weig~t percent of the plasticizer. Polyethylene ~lycol can compri~e up to 100 weight p~arcent of the pla~ticizer.
Polyethylene glycol of either 300 molecular weight or 400 molecular weight is preferred with 300 molecular weight more preferred.
When the adhesive composition~ are used a~ an electrically conductive component of biomedical electrode~, the pla~ticizer can al~o opticnally includ~a water to improve ionic conductivity in the compo~ition and can include either glycerin or polyethylene glycol. In thi~ in~tance, water i3 u~ed as a pla~ticizer comprising from about 20 ~3rce~t to about 100 percent and preferably at least about 30 per~el~t by weight of the plaQticizer used.
Bioco~patible and/or Therapeutic and/or~Ionically- C nductive ~dditives Depending upon the u~e of the hydrophilic, pre~ure-~ensitive adhesive compo~ition of the present inv2ntion, variou~
biocompatible and~or therapeutic and/or ionically conductive ~-material~ can ~e included in the compo~ition~
For example, composition3 of the present invention can be u0ed as conductive adhesive in a ~iomedical electrode with the addition of an ionically conductive elçctrolyte to the compo~ition -~
after radiation-cro~slinking of the ~olid poly(N vinyl lactam) with ionizing radiation without deleteriously affecting the el~ctrolyte or the resulting compo~itionO Nonlimiting examples of electrolyte include ionic salts dissolved in the composition to provide ionic conductivity and can include lithi~m chloride, lithium perchlorate, ~odium citrate, and preferably pot~aium chloride. Alternatively, a redox couple such as a mixture of ferric and ferrou~ salt3 such a~
sulfate~ and giuconate3 can be added.
_g~
WO ~5J1()201 PCT/USg~/lJ~3g7 ~ IL 161~ 3 ~he ~mount~ of the~e ionic ~altB pre~ent in compo~itior, of the pre~ent invention ~re relatively ~mall, from about 0.5 to 5 percent ~y wei~h~ of the composition, and preferably about 2 to 3 weight percent. When a redox couple i~ used in compo~itions of th~
pre~ent invention, the biomedical electrode can recover from an overload potential. U.S. Pat. No. 4,846,185 ~Carim) di~close3 a redox couple totalling not more than about 20 percent by weight of the adhesive compo~ition.
Hydrophilic, pres~ure-~en~itive adhesive compositions of the pre~ent lnvention can also be used in the delivery of pharmaceuticals to or through mammalian ~kin, ~uch as topical or tran~dermal drug delivery ~ystem~. The pharmaceutical or other active ingredient can be compounded with the adhesive compo~ition after poly(N-vinyl lactam~ has been radiation-crosslinked, minimizing any po~ible deleterious interaction of the pharmaceutical or active ingredient with ionizing radiation in do0age~ ~ufficient to crosslink poly~N-vinyl lactam~.
A type of therapeutic proc~dure both involving application of electrical current to skin of a patient and a pharmaceutical is iontophoresis, which deliver~ an iontophoretically active pharmaceutical to or through mammalian skin with aid o~ an electrical current.
The hydrophil~c, pre~sure-sen~itive adhesive composikion can al~o be u~ed in therapeutic mammalian skin coverings, ~uch as drassings, wound clo3ur~ materials, tapea, and the like.
Preferably, for mammalian ~kin covering u~es, other biologically active materials ~an be added to the compo~ition of the pre~ent invention after irradiation of polylN-vinyl lactam~ without deleteriously ~ffecting the biologically a~tive material. .
Nonlimiting example~ of ~uoh other biologically active materials include hroad spectrum antimicrobial agents where it is de~ired to -reduce bacteria lev~ls to minimize infection risk or treat the ePfects of infPction~ at the ~kin or 3kin opening~ of a mammalian , patient. Broad Bpectrum antimicrobial agent~ re di3clo~ed in ~.S.
pat. No. 4,310,5090 Nonlimiting example~ of other antimicrobial agent~ include parachloromQtaxylenol; triclo~an; chlorhexidine and it~ ~alts ~uch a~ chlorhexi~ine acetate a~d chlorhexidin~ gluoonate;
iodine; iodophor~; poly-N-vinyl pyrrolidone-iodophors; ~ilver oxide, ~ilver and its 8alt8~ antibiotic8 (e~g., neomycin, bacitxacin, and polymyxin B). Antimicrobial a~ents can be included in the compo3ition af~er radiation of poly~N-vinyl lactam~ in a weight from -about 0.01 percent to about 10 peroent by wei~ht of the total ~ ;
eompo~ition O~her biocompatible and/or therapeutic material~ can be added to the composition such as compounda to buffer ~he pH of the composition to provide a non-irritating pH for use with eenBitive -10~
W~ 2 ~1612 3 P~r/uss2/o~3~7 mammalian ~kin tin~ue or to otherwi~e maximize antimicrobial activity. Also, penetration enhancing agents or excipient~ can be added to the composition when the pharmaceutical or other active agent for topical or tran~dermal deli~ery ~o requires.
Irradiation Cros~llnkin~ of_Poly(N-Viny~_~s~8m~
Poly~N-vinyl lactam) in any ~olid form i~ ~ubjected to ionizing radiation from a high-energy source. Nonlimiting exiample~
of ionizing radiation include alpha, beta, gamma, electron-beiam, and x-ray radiation. 0~ the~e ~ources of ionizing radiation, electron-beam irradiation and gi~mma irradiation are pre~erred. Sources of electron-beiam radiation are commerc~ally available, includtng an Energy Sciences Inc. ~odel CB-150 Electrocurtain Electron Beam Proces~or. SOurCeB of qi~mm~ irradiation are commercially available from Akomic Energy of Canada, Inc. u~ing a cobalt-60 high-ener~y cource.
lonizing radiation dn~ages are mea~uxed in megarad~
(mRad) or kilogxay~ (kGy). Dose~ o~ ionizing radiiation can be administered in a ~ingle do~e of the d~sired level of ionizing radiation or in multiple do~e~ which accumulate to the desired level of ionizing radiation. The do~age o ionizing radiation ~umulatively can range rsm about 25 kGys to about 400 kGy~ and pxeerably from about 25 ~Gy~ to about 200 kGy~. Pref~rably, ionizing radlation can achieve the de~ired level of crosslinking of poly(~-vinyl lactam) when the cumulative do~age of ionizing radiation ~xceeds 100 kGys (10 mRad~.
Poly~N-vinyl lactam~ can be irr di~ted in a 801id form wlth ioni~ing radiation in a package or container where the temperature, atmosphere, and other reaotion parameter~ can be controlled.
Temperature can range from about -80C to about lQODC `~;~
and preferably from about 10C to ab~ut 35C.
The atmo~pher~ can be air or preferably an inert a~mo~phere ~uch a~ nitrogen.
3~ The line ~peed for electron-beam irradiation can be about 15 meters/minu~e.
The pressure in the container can be atmo~pheri~, ele~ated or depre~ed. Preferably it i9 atmospheric.
Depending upon the control of the irradiation i ~onditions, poly(N~vinyl l~ctam) can be irradiated in a batch ~r con~inuou~ proce~
:
ethod o~ P~reParl~q-~y~r~hL~llc~ Pre~ure=~ Sly~_~
ComPo~ition3 A m~thod of preparing a hydrophilic, pres~ure-sen~ikive ~ ;
adhe~ive composition of the present invention can employ a minimum ,.
--11-- ~ . ;
` ;~' wo ~ 2~1 PC~/lJS~/0~3~7 number of ~co10gica11y comp~tibl~ manufacturing step~. The solid, radlatlon-cro~lLnked poly~N-vinyl lactam) i~ mixed wi~h ~entially unirradiated pla~ticiz~ and any oth~r optional additive~ into a ~olvent which iB es~entially volatile at or above ambient temperature~, ~uch as water~ athanol, methanol, and i30propanol. A
quantity of the ~u~penQion of radiation-cros~linked poly(N-vinyl lactam)~ eseentially unirradiated plasticizer, and any optional additive~ in the volatile solvent is then cast onto a ~urface of a substrate, which can be an inert sub~trate such a~ a liner for ~torage before further proce~sing or a ~urface d~signed for ultimate use, auch ~ a mean~ for electrical communication havLng an electrically conductive surface for u~e a~ a biomedical electrode.
Then the volatile ~olvent i~ essentially evaporated by the applLcation of heat, microwave energy, infrared energy, convective air flow or the like, in order to form a cohesive, pressure-sensitive adhe~ive compo~ition on the ~ub~trate.
Typically, a drying oven heated to about 65C can be employed. A
product liner can optionally be larninated over the field of pr~nsure-~ensit:L~e adhesive composition to protect that field from contamination.
~ coating of cohesive, prel3sure-sen~itive adhe~ive compo~ition can be applied to a Qub3trate surface. Coating thickna~o~ can range from about 0.125 mm to about 1.25 mm and preferably ~rom about ~.75 mm to about 1 mm, to yield a~ter evaporation of Qolvent a coating thich~Q~s ranging from about 0.05 mm to about 0.38 r~n and preferably from about 0.18 mm to bout 0.25 mm. With thi~ extremely thin coati~g of a conductive and preferably adhesive composition, a low profile and conformable biomedical electrode can be made.
3n The method can be prepared in a batch proce~s or in a continuous line process. If prepared by a continuouQ proce~, the ~ ;
laminate of a liner, field of cohe~ive, pre~3ur~-sensitive adhe~ive ~ :
compo~ition~ and 3ubstrate can be wound on a roll for bulk packaging , and further pr*ce~ing or can be cut u~ing dies known to thoee ~kill~d in the art into individual unit~r ~uch a~ biomedical electrode~ or biomedical electrode ~ubassemblie~, for furth~r proce~sing. U.S. Pat. No. 4,795,516 (Strand) and U.S. Pat. No.
4,798,642 (craighead et al.) di9cloBe pXOCeBBe8 and equipment useful for a continuou~ m~nufacture of biomedical electrod2~ involving the dispen~ing of strips of material from roll9 a~d overlaying such 8trip9 in a regi~tered ContinuouB manner in oxder to pr~pare a ~trip of electrodes.
For ~xample, one me~hod of continuous strip as~embly can be the coating of an aqueous mixture o radiation-cro~slinked poly(N vinyl pyrrolidone), polyethylene glycol, and pota~sium chloride on an electrically conductive ~urface about 809 cm wide, ;~
-1~- ,.'~ . ' ,~-"'''' , - .
W ~ fll 2 1 1 6 1 ~ 3 PCT/US9~/~9397 wlth thQ coatl~g appliad to about the center 5.1 cm ~ection of ~uch ~idth. After evsporation of sol~ant, the coated electrically conductive surface can be bisected along the strip a~d also cut orthogonally at about 2.54 cm intervals, yielding a number of electrodes 10 seen in Fig. 1 having dimension~ of about 2.54 cm x ~.4 cm with a conductive interface portion 18 of 2~54 cm x 2.54 cm and a tab portion 20 of 2.54 cm x 1.9 cm.
U~efulne~ of the Invention Hydrophilic, pra~ure-~ensitive adhesi~e composition~ of the present invention can have many uses as biocompatible medical adhe~ive~ ~uch a~ for rece~pt or delivery of electrical signal~ at or throuqh mammalian ski~, delivery of pharmaceuticals or acti~e agents to or through mammalian skin, or treatment of mammalian skin or mammalian skin openings again~t the pos~ibilitie~ of infection.
Biomedical Elec rode~
Biomedical electrode~ employing hydrophilic, pressure-~ensitive adhesive compo~itions of the present invention having electrolyte contained therein are usaful for diagno~tic and therapeutic purpo~e~. In its most basic form, a biomedical electrode compri~e~ a co~ductive medium contacting mammalian skin and a mean~ for electrical communication interacting batween the conductive medium and electrical diagno~ticr therapeutic, or electrosurgical equipment.
FIGS. 1 and 2 ~how either a dispo~able diagno tic electrocardiogram (ECG) or a tran~cutaneou~ electrical nerve ~timulation (TENS) electxode 10 on a relea~e liner 12. Electrode 10 include~ a field 14 of a biocompatible and adhesive c~nductive medium for contactin~ mamm~lian skin of a patient upon removal of protective relea~e liner 12. Electrode 10 include~ means for electrical com~unication 16 comprising a conductor memb~r having a conductive inter~ace portion 18 contactin~ field 14 of conductive medium and a tab portion 20 extending beyond field 14 of conductive ~5 madium for mechanical and electrical contact with electrical in3trumentation (not ~hown)~ ~ean~ 16 for electrical communication include~ a conductive layer 26 coat~d on at lea~t the ~ide 22 contacting field 14 of conductive medium.
~ It is fore~een that a typical ~CG conductor me~ber 1~
will comprise a strip o ma~erial having a thickne~ of about 0.05-0.2 millimeter~, ~uch a~ polye8ter film and have a coating 26 on side 22 o ~ilver/~ilver chloride of about 2.5-12 micrometer , and preferably about 5 micrometer8 thick thereon. Pre~ently preferred i~ a polyester film commercially available as "~elIinex~ 505-300, 329, or 339 film from ICI ~mericas ~ Hopewell, ~A coated with a ~Llver/~llver chloride i=L ~o~merc-ally available a~ "R-300~' ink WC~ i PCr/US~/0~3~7 2 11~123 from Ercon, Inc. of Waltham, MA. A TENS conductor member 16 can b~
made of a nonwoven web, ~uch a~ a web of polye~ter/cellulose fibers commercially available as "Manniweb" web from Lydall, Inc. of Troy, NY and have a carbon ink layer 26 commercially ~vailable a~
"SS24363" ink from Acheson Colloida Company of Port Huron, MI on side 22 thereof. To enhance mechanical contact between an electrode clip ~not shown~ and conductor member 16, an adhesively-backed polyethylene tape can be applied to tab portion 20 on side 24 opposite side 22 having the conductive coating 26. A surgical tape -~
commercially available from 3M Company a~ nBlenderm" tape can be emp7Oyed for thi~ purpoae.
Mon-limiting examples of biomedical electrodes which can use hydrophilic, pressure-~ensitive adhe~ive compo~itions of the present invention, either a4 conductive or non-concluctive adhesive fields include electrodes disclosed in U.S. Pat. ~o~. 4,527,087;
4,539,996, 4~554,924; 4,848,353 (all Engel~; 4,846,185 (Carim);
4,771,713 ~Robert~); 4,715,382 (Strand); 5,012,810 (Strand et al.);
and 5,133,355 (~ryan et al.)~
In ~om~ inRtances, the means for el~ctrical communication can be an electri~ally conductive tab extending from the periphery of the biomedical ~lectrodes such a~ that ~e~n in U.S.
P~t. No. 4,848,353 or can be a conductor member extending throu~h a slit or seam in an in~ulating backing rnember, such as that ~eerl in U.S. Pat. No. 5,012,810. Otherwise, the mean~ for electrical communication can be an eyelet or other snap-type connector ~uch aB
that disclo3ed in U.S. Pat. No. 4,846,185. Further, the m~ans for electrical communication ca~ be a lead wire ~ch a~ that ~een in ~-U.S. Pat. No. 4,771,783. Regardless of the type of meanR ~or electrical communication employed, a hydrophilic, pres~ure-sensitive ~
adhesive composition of the pre~ent invention, containing an ~ -electrolyte, can reside as a ~ield of con~uctive adhesiv~ on a biom~dical electrode for diagno~tic, therapeutic, or elec~ro~urgical purpo3es. -~
edical Skin Coverin~
Medical ~kin covering~ employing hydrophilic, pres~ure-sen~itive adhesive compo~ition~ of the present inventiQn, optionally havlng antimicrobial and other biologically active agent~ contained therein, are useful for treatment of mammalian ~kin or mammalian ~kin openingsJ preferably against the po~ibility of infection.
FIG. 3 shows a ~ectional view of a medical ~kin covering 30 having a backing ~aterial 32, a layer 34 of pres9ure-~ensitive adhe~i~e compo9ition of the pre~ent inventio~ coated on ba~kiny ma~erial 32, and protected until u~e by a relea6e liner 36.
Preferably, antimicrobial 38 i8 contained in layer 34 by adding agent 38 to e~sentially unirradiated pla3ticizer or co~po~ition -14~
','"'"'' . . - ~
2 1 1 S 1 2 3 PCl/US~2/09397 prior to coating on bac~ing material 32. Alternativ~ly, layer 34 can be u~ed a~ a caulkable ~ealant ~ccording to u.s. Pat. No.
4,931,282 (A~mu~ et al~).
For u~, the release liner 36 i~ removed and the layer 34 of pressure-~ensitive adhe~ive compo~ition can be applied to the ~kin of the patient a~ a part of a medical tape, a wound dre~sing, a bandage of general medicinal utility, or other madical device having water moi~ture ab~orbing propertie~.
The adhesive layer 34 may be coated on a layer of backing material 32 selected from any of se~eral backing materials having a high moi~tur~ vapor transmission rate for u~e a~ medical tapea, dres~ings, bandage~, and the like. Suitable backing material~ include those di~clo~ed in U.S. Patent3 3,645 t 835 and 4,595,001. Othar example~ of a variety of film~ commercially a~ailable aq extrudable polymer~ include ~HytrelR 4056" and "Hytrol~ 3548" branded polyester elastomers available from E. I .
DuPont de Nemours and Company of ~ilmington, Delaware, "Estane"
branded polyurethanes available from B~F. Goodrich of Cleveland, Ohio or "Q-thane~ branded polyurethanes available from K.J. Quinn Co. of Maldenr Ma~achusetts.
The layer 34 of adhesive combined with a layer 32 of 0uitable backing material can be u~ed a~ a dre~sing.
Hydrophilic, pre~sure-sensitive adhe~ive composition~ of the present invention can be used a~ discrete gel particles disper~ed in a continuou~ pressure-sen~iti~e adhe~ive matrix to form a two pha~e compo~ite u~eful in medical applications, a~ deacribed in co-pending, co-a~signed International Application Serial No 4 7 0 7 5PCTlA .
The adhe~ive layer 34 can be coated on the backing layer 32 by a variety of proce~3e~, including, direct coating, lamination, and hot lamination. The relea~e liner 36 can ~hereafter be applie~
using direct coating, lamination, and hot laminationO -~
The methods of lamination and hot lamination involve the ' application of pre~sure, or heat and pre~sure, re~pectively, on the layer of adhesive layer 34 to the backin~ material layer 32. Th~
temperature for hot lamination ranges from about 50C ~o about ;~
250CJ and the pressures applied to both lamination and hot f lamination range from 0.1 Rg/cm2 to about 50 Rg/cm2.
Pharm~aceutical Deliverv Device~
Pharmaceutical deliv~ry device~ employing hydrophilic, pre~sure-3ensitive adhesive compo~ition~ o the pr~ent inve~tion, optionally having a topical, tran~dermal, or iontophoretic therapeutic agent and ~xCipie~t~, 801vent8, or p~netration enhancin~
4S agent~ contained therein, are useful for delivery of pharmaceutical~
~ . ~
W ~ r/U~9~/01~3~7 or other activc ayent~ to ~r through mammalian skin.
FIG. 4 showe a E~ectional vi~3~ of a transdermal or topical drug deli~ery device 40 having a backing layer 42, a layer 4~ containing hydrophilic, pre~sure-~ensitive adhs~ive compo0ition of the present invention coated thereon and protected by a relea~e liner 46. Other layers can be present b~tween layer 42 and layer 44 to house pharmaceutical~ or other therapeutic agent~. Otherwise, as shown in FIG. 4, pharmaceutical and other agent~ 48 ar~ di~persed in adhesive layer 44.
The backiny layer 42 can be any backing material known to tho~e ~killad in the art and u~e~ul for drug delivery device~. :
Non-limiting examples of ~uch backing material~ are polyethylene, ethylene-vinyl acetate copolymer, polyethylene-aluminum-polyethylene composite~, and ~ScotchPak1~" brand backin~ commercially available from Minne~ota Mining and Manufacturing Company of St. Paul, Minnesota (3M).
The release liner 46 can be any relea3e liner material known to tho~e ekilled in the art. Non-limiting example3 of such release liners commercially available include siliconized polyethylene terephthalate ~ilm~ commercially available from H.P.
Smith Co. and fluoropol~mer coated polye~ter film~ commercially available from 3~ und~r the brand "ScotchPak ~ n relea~e liners. ~:
The therapeutic agent 48 can be any therapeutically active material known to tho~e skilled in the art and approved for delivery topically to or transdermally or iontophoretically through the ~kin of a patient. Non-limiting example~ of therapeutic agents u~eful in transdenmal d~livery devic~ are any active drug or sal~s ~:
of tho~e drug~, used in topical or tran~dermal application~, or ; ~
growth factor~ for use in enhancing wound healing. Other : :-therapeutic a~ent~ identified as drugs or pharmacolo~ically active a~ent~ are di~closed in U.S. Patent No~. 4,849,224 and 4,855,294, :~
and PCT Patent Publication WO 8~/07951.
Excipients or penetration enhancing agents are also :
known to tho~e ~killed in the art. Nsn-limiting examples of penetration enha~cing ag2nts include ethanol, methyl laurate, oleic acid, i~opropyl myristate, and glycerol monola~rateO Other penetration enhancing ag2nts known to tho~e ~killed in the art ar~
disclo~ed in U.S. Patent Nos. 4,849,224; an~ 4,855,294 and PCT
Patent Publication ~0 89J07951.
The method of manufacturin~ a transdermal delivery :~
device depends on it~ con~truction~
The drug delivery device 40 shown in FIG. 4 ~an be :~
prepared using the following gen~ral method. A 301ution i3 prepared by di~olvlng the therapeutlc ag~nt 48 ~nd ~uch optional excipient~
as are desired in a ~uitable ~olvent and mixed in~o either es~entially unirradàated pla~ticizer prior to forming the ~
~ , :
-'.''~"' w~g~lo~ 2~16123 PCr/VS~2/O~Q7 compo~ltion, durLnc3 the formation of the compo~itio~, or directly into the already formed compoAition. The resulting loaded adhasive composition i~ coated on the backing layer 42. A relea~e liner 46 L~ applied to cover loaded adhe~ive layer 44.
A further d~cription of the inv~ntion may be found in the following exampl~s.
Examples A number of example~ of adhe~ive compo~itions of the present invention were prepared according to a process of the pre~ent invention. Approximately 100 grams of noncrosslinked poly~N-vinyl pyrrolidone) in a ~olid form of particles having a ~ize of about 10 ~m were placed in a re~alable plastic bag and, except for ~omparative Example 8, were irradiated with ionizin~ xadiation according ~o the irradiation type and dosage ~hown in Table I, followed by mixing of the re~ulting ~olid, radiation-cro~alinked polylN-vinyl pyrrolldone) homopolymer with a pla~ticizer of glycerin, water, or a mixture thereof~ For irradiation by E-beam, an ~nergy Sciences Inc. Model CB-150 Electrocurta.in Electron Beam Proce~sor operating at a line speed of about 15 meters/minute and at 250 kV ~except for ~xample 1 operating at 200 ~v) wa3 us~d at c~mbient temperature and preasure. For radiation for Example~ 9-12 u~ing gamma radiation, an Atomic Energy of Canada, Inc. Model ~S-7500 machine u~ing a cobalt-60 hig]h-energy ~urce at ambient temperature and pre~ure.
Table I show~ the re~ulting adhesive compo~i~ion~ and observations about the re~ulting adhel3ive compo~ition.
~17 W~ I Pf/US~2t~3~ 7 21 16123 ;
~ 11~
I ~ .~ ~ ~ v= ,~ ~,v ~ ~ 1 ;~
For ~xample, one me~hod of continuous strip as~embly can be the coating of an aqueous mixture o radiation-cro~slinked poly(N vinyl pyrrolidone), polyethylene glycol, and pota~sium chloride on an electrically conductive ~urface about 809 cm wide, ;~
-1~- ,.'~ . ' ,~-"'''' , - .
W ~ fll 2 1 1 6 1 ~ 3 PCT/US9~/~9397 wlth thQ coatl~g appliad to about the center 5.1 cm ~ection of ~uch ~idth. After evsporation of sol~ant, the coated electrically conductive surface can be bisected along the strip a~d also cut orthogonally at about 2.54 cm intervals, yielding a number of electrodes 10 seen in Fig. 1 having dimension~ of about 2.54 cm x ~.4 cm with a conductive interface portion 18 of 2~54 cm x 2.54 cm and a tab portion 20 of 2.54 cm x 1.9 cm.
U~efulne~ of the Invention Hydrophilic, pra~ure-~ensitive adhesi~e composition~ of the present invention can have many uses as biocompatible medical adhe~ive~ ~uch a~ for rece~pt or delivery of electrical signal~ at or throuqh mammalian ski~, delivery of pharmaceuticals or acti~e agents to or through mammalian skin, or treatment of mammalian skin or mammalian skin openings again~t the pos~ibilitie~ of infection.
Biomedical Elec rode~
Biomedical electrode~ employing hydrophilic, pressure-~ensitive adhesive compo~itions of the present invention having electrolyte contained therein are usaful for diagno~tic and therapeutic purpo~e~. In its most basic form, a biomedical electrode compri~e~ a co~ductive medium contacting mammalian skin and a mean~ for electrical communication interacting batween the conductive medium and electrical diagno~ticr therapeutic, or electrosurgical equipment.
FIGS. 1 and 2 ~how either a dispo~able diagno tic electrocardiogram (ECG) or a tran~cutaneou~ electrical nerve ~timulation (TENS) electxode 10 on a relea~e liner 12. Electrode 10 include~ a field 14 of a biocompatible and adhesive c~nductive medium for contactin~ mamm~lian skin of a patient upon removal of protective relea~e liner 12. Electrode 10 include~ means for electrical com~unication 16 comprising a conductor memb~r having a conductive inter~ace portion 18 contactin~ field 14 of conductive medium and a tab portion 20 extending beyond field 14 of conductive ~5 madium for mechanical and electrical contact with electrical in3trumentation (not ~hown)~ ~ean~ 16 for electrical communication include~ a conductive layer 26 coat~d on at lea~t the ~ide 22 contacting field 14 of conductive medium.
~ It is fore~een that a typical ~CG conductor me~ber 1~
will comprise a strip o ma~erial having a thickne~ of about 0.05-0.2 millimeter~, ~uch a~ polye8ter film and have a coating 26 on side 22 o ~ilver/~ilver chloride of about 2.5-12 micrometer , and preferably about 5 micrometer8 thick thereon. Pre~ently preferred i~ a polyester film commercially available as "~elIinex~ 505-300, 329, or 339 film from ICI ~mericas ~ Hopewell, ~A coated with a ~Llver/~llver chloride i=L ~o~merc-ally available a~ "R-300~' ink WC~ i PCr/US~/0~3~7 2 11~123 from Ercon, Inc. of Waltham, MA. A TENS conductor member 16 can b~
made of a nonwoven web, ~uch a~ a web of polye~ter/cellulose fibers commercially available as "Manniweb" web from Lydall, Inc. of Troy, NY and have a carbon ink layer 26 commercially ~vailable a~
"SS24363" ink from Acheson Colloida Company of Port Huron, MI on side 22 thereof. To enhance mechanical contact between an electrode clip ~not shown~ and conductor member 16, an adhesively-backed polyethylene tape can be applied to tab portion 20 on side 24 opposite side 22 having the conductive coating 26. A surgical tape -~
commercially available from 3M Company a~ nBlenderm" tape can be emp7Oyed for thi~ purpoae.
Mon-limiting examples of biomedical electrodes which can use hydrophilic, pressure-~ensitive adhe~ive compo~itions of the present invention, either a4 conductive or non-concluctive adhesive fields include electrodes disclosed in U.S. Pat. ~o~. 4,527,087;
4,539,996, 4~554,924; 4,848,353 (all Engel~; 4,846,185 (Carim);
4,771,713 ~Robert~); 4,715,382 (Strand); 5,012,810 (Strand et al.);
and 5,133,355 (~ryan et al.)~
In ~om~ inRtances, the means for el~ctrical communication can be an electri~ally conductive tab extending from the periphery of the biomedical ~lectrodes such a~ that ~e~n in U.S.
P~t. No. 4,848,353 or can be a conductor member extending throu~h a slit or seam in an in~ulating backing rnember, such as that ~eerl in U.S. Pat. No. 5,012,810. Otherwise, the mean~ for electrical communication can be an eyelet or other snap-type connector ~uch aB
that disclo3ed in U.S. Pat. No. 4,846,185. Further, the m~ans for electrical communication ca~ be a lead wire ~ch a~ that ~een in ~-U.S. Pat. No. 4,771,783. Regardless of the type of meanR ~or electrical communication employed, a hydrophilic, pres~ure-sensitive ~
adhesive composition of the pre~ent invention, containing an ~ -electrolyte, can reside as a ~ield of con~uctive adhesiv~ on a biom~dical electrode for diagno~tic, therapeutic, or elec~ro~urgical purpo3es. -~
edical Skin Coverin~
Medical ~kin covering~ employing hydrophilic, pres~ure-sen~itive adhesive compo~ition~ of the present inventiQn, optionally havlng antimicrobial and other biologically active agent~ contained therein, are useful for treatment of mammalian ~kin or mammalian ~kin openingsJ preferably against the po~ibility of infection.
FIG. 3 shows a ~ectional view of a medical ~kin covering 30 having a backing ~aterial 32, a layer 34 of pres9ure-~ensitive adhe~i~e compo9ition of the pre~ent inventio~ coated on ba~kiny ma~erial 32, and protected until u~e by a relea6e liner 36.
Preferably, antimicrobial 38 i8 contained in layer 34 by adding agent 38 to e~sentially unirradiated pla3ticizer or co~po~ition -14~
','"'"'' . . - ~
2 1 1 S 1 2 3 PCl/US~2/09397 prior to coating on bac~ing material 32. Alternativ~ly, layer 34 can be u~ed a~ a caulkable ~ealant ~ccording to u.s. Pat. No.
4,931,282 (A~mu~ et al~).
For u~, the release liner 36 i~ removed and the layer 34 of pressure-~ensitive adhe~ive compo~ition can be applied to the ~kin of the patient a~ a part of a medical tape, a wound dre~sing, a bandage of general medicinal utility, or other madical device having water moi~ture ab~orbing propertie~.
The adhesive layer 34 may be coated on a layer of backing material 32 selected from any of se~eral backing materials having a high moi~tur~ vapor transmission rate for u~e a~ medical tapea, dres~ings, bandage~, and the like. Suitable backing material~ include those di~clo~ed in U.S. Patent3 3,645 t 835 and 4,595,001. Othar example~ of a variety of film~ commercially a~ailable aq extrudable polymer~ include ~HytrelR 4056" and "Hytrol~ 3548" branded polyester elastomers available from E. I .
DuPont de Nemours and Company of ~ilmington, Delaware, "Estane"
branded polyurethanes available from B~F. Goodrich of Cleveland, Ohio or "Q-thane~ branded polyurethanes available from K.J. Quinn Co. of Maldenr Ma~achusetts.
The layer 34 of adhesive combined with a layer 32 of 0uitable backing material can be u~ed a~ a dre~sing.
Hydrophilic, pre~sure-sensitive adhe~ive composition~ of the present invention can be used a~ discrete gel particles disper~ed in a continuou~ pressure-sen~iti~e adhe~ive matrix to form a two pha~e compo~ite u~eful in medical applications, a~ deacribed in co-pending, co-a~signed International Application Serial No 4 7 0 7 5PCTlA .
The adhe~ive layer 34 can be coated on the backing layer 32 by a variety of proce~3e~, including, direct coating, lamination, and hot lamination. The relea~e liner 36 can ~hereafter be applie~
using direct coating, lamination, and hot laminationO -~
The methods of lamination and hot lamination involve the ' application of pre~sure, or heat and pre~sure, re~pectively, on the layer of adhesive layer 34 to the backin~ material layer 32. Th~
temperature for hot lamination ranges from about 50C ~o about ;~
250CJ and the pressures applied to both lamination and hot f lamination range from 0.1 Rg/cm2 to about 50 Rg/cm2.
Pharm~aceutical Deliverv Device~
Pharmaceutical deliv~ry device~ employing hydrophilic, pre~sure-3ensitive adhesive compo~ition~ o the pr~ent inve~tion, optionally having a topical, tran~dermal, or iontophoretic therapeutic agent and ~xCipie~t~, 801vent8, or p~netration enhancin~
4S agent~ contained therein, are useful for delivery of pharmaceutical~
~ . ~
W ~ r/U~9~/01~3~7 or other activc ayent~ to ~r through mammalian skin.
FIG. 4 showe a E~ectional vi~3~ of a transdermal or topical drug deli~ery device 40 having a backing layer 42, a layer 4~ containing hydrophilic, pre~sure-~ensitive adhs~ive compo0ition of the present invention coated thereon and protected by a relea~e liner 46. Other layers can be present b~tween layer 42 and layer 44 to house pharmaceutical~ or other therapeutic agent~. Otherwise, as shown in FIG. 4, pharmaceutical and other agent~ 48 ar~ di~persed in adhesive layer 44.
The backiny layer 42 can be any backing material known to tho~e ~killad in the art and u~e~ul for drug delivery device~. :
Non-limiting examples of ~uch backing material~ are polyethylene, ethylene-vinyl acetate copolymer, polyethylene-aluminum-polyethylene composite~, and ~ScotchPak1~" brand backin~ commercially available from Minne~ota Mining and Manufacturing Company of St. Paul, Minnesota (3M).
The release liner 46 can be any relea3e liner material known to tho~e ekilled in the art. Non-limiting example3 of such release liners commercially available include siliconized polyethylene terephthalate ~ilm~ commercially available from H.P.
Smith Co. and fluoropol~mer coated polye~ter film~ commercially available from 3~ und~r the brand "ScotchPak ~ n relea~e liners. ~:
The therapeutic agent 48 can be any therapeutically active material known to tho~e skilled in the art and approved for delivery topically to or transdermally or iontophoretically through the ~kin of a patient. Non-limiting example~ of therapeutic agents u~eful in transdenmal d~livery devic~ are any active drug or sal~s ~:
of tho~e drug~, used in topical or tran~dermal application~, or ; ~
growth factor~ for use in enhancing wound healing. Other : :-therapeutic a~ent~ identified as drugs or pharmacolo~ically active a~ent~ are di~closed in U.S. Patent No~. 4,849,224 and 4,855,294, :~
and PCT Patent Publication WO 8~/07951.
Excipients or penetration enhancing agents are also :
known to tho~e ~killed in the art. Nsn-limiting examples of penetration enha~cing ag2nts include ethanol, methyl laurate, oleic acid, i~opropyl myristate, and glycerol monola~rateO Other penetration enhancing ag2nts known to tho~e ~killed in the art ar~
disclo~ed in U.S. Patent Nos. 4,849,224; an~ 4,855,294 and PCT
Patent Publication ~0 89J07951.
The method of manufacturin~ a transdermal delivery :~
device depends on it~ con~truction~
The drug delivery device 40 shown in FIG. 4 ~an be :~
prepared using the following gen~ral method. A 301ution i3 prepared by di~olvlng the therapeutlc ag~nt 48 ~nd ~uch optional excipient~
as are desired in a ~uitable ~olvent and mixed in~o either es~entially unirradàated pla~ticizer prior to forming the ~
~ , :
-'.''~"' w~g~lo~ 2~16123 PCr/VS~2/O~Q7 compo~ltion, durLnc3 the formation of the compo~itio~, or directly into the already formed compoAition. The resulting loaded adhasive composition i~ coated on the backing layer 42. A relea~e liner 46 L~ applied to cover loaded adhe~ive layer 44.
A further d~cription of the inv~ntion may be found in the following exampl~s.
Examples A number of example~ of adhe~ive compo~itions of the present invention were prepared according to a process of the pre~ent invention. Approximately 100 grams of noncrosslinked poly~N-vinyl pyrrolidone) in a ~olid form of particles having a ~ize of about 10 ~m were placed in a re~alable plastic bag and, except for ~omparative Example 8, were irradiated with ionizin~ xadiation according ~o the irradiation type and dosage ~hown in Table I, followed by mixing of the re~ulting ~olid, radiation-cro~alinked polylN-vinyl pyrrolldone) homopolymer with a pla~ticizer of glycerin, water, or a mixture thereof~ For irradiation by E-beam, an ~nergy Sciences Inc. Model CB-150 Electrocurta.in Electron Beam Proce~sor operating at a line speed of about 15 meters/minute and at 250 kV ~except for ~xample 1 operating at 200 ~v) wa3 us~d at c~mbient temperature and preasure. For radiation for Example~ 9-12 u~ing gamma radiation, an Atomic Energy of Canada, Inc. Model ~S-7500 machine u~ing a cobalt-60 hig]h-energy ~urce at ambient temperature and pre~ure.
Table I show~ the re~ulting adhesive compo~i~ion~ and observations about the re~ulting adhel3ive compo~ition.
~17 W~ I Pf/US~2t~3~ 7 21 16123 ;
~ 11~
I ~ .~ ~ ~ v= ,~ ~,v ~ ~ 1 ;~
5~ e" ¦
S U O O h m ~:: :- e ~ E~-l ' .rl ~rl tO ~J m ~ ~ ~ ~ ~ ~ ~ _ .C ::~ ~ ~ ~1 ~> ~ ., ~ h 11~ ., ., ¦ E
I ~ r _ ~ E
I O O O O O ~
¦ ~ o O~ O~ ~: _I O o o , ~ ~ ~ ¦ E ^ C
~ El ~ dP oP ~P dP U~ d~ dQ dP cP ~o ~P oP I 01~
~C K X X X X X X X X XX ¦ E
dP oP d~ d~ dQ dP dP dP ~P dP d? d~ I I :~
O o o ~ ~ ~ ~ ~ O O oO ~ ,-1 ~ Z - ' ' ' t~ ~ ~ ~ ~ r~ t~ r~ ~ ~~ I
l 8 ~ o ~ o o O N C) ul O O N I N
r ~
1 ` C PE~ o~
~ 1 ¦_ _ _ _ _ _ _ _ _ _~. _ ~ O ~
a ~ ~ ~ ~ ~ a~ e ~ a ~ ~ oJ r7 7 ~
O I_ _ __ _ _ _ __ _ _ _ ~ ~ O ~ O ~ t t4 l ~C O r~ ~ ~0 i I I .'~
= ~a~ L N __ __ __ _C _ __ V~
X U ' ' ','' ' ''~
W ~{~t~2~11 2 ~ PCT/U~92/0~3~7 Example~ 1-3 demon~trate the ef~ect of irradiation do~age and it~ effect on the cro~linking of PVP. Increasing irradiation do~aye increa~es the vi3c08ity ~nd cohe~ivene~s of the adhe~ive composition, all other compositional parameters remaining S const~nt.
~xamples 4-6 demon~trate the difference~ in adhesive composition properties based on variation of the mixture of plasticizer~ A~ the weight percentage of water increa~es, the visco~ity and cohesiveness of the adhesive decrea~e~, balan~ed by a decrease in adhe~iveness.
Example 7 and Compari~on Example 8 compare th~ effect of irradiation a~cording to the prOcQss of th~ pre~ent invention. All other parameters being constant, the ab~ence of irradiation of linear PVP fail to achieve adhesive properties required for the lS pre~ent invention. ~urther, a comparison of Example 7 with Example
S U O O h m ~:: :- e ~ E~-l ' .rl ~rl tO ~J m ~ ~ ~ ~ ~ ~ ~ _ .C ::~ ~ ~ ~1 ~> ~ ., ~ h 11~ ., ., ¦ E
I ~ r _ ~ E
I O O O O O ~
¦ ~ o O~ O~ ~: _I O o o , ~ ~ ~ ¦ E ^ C
~ El ~ dP oP ~P dP U~ d~ dQ dP cP ~o ~P oP I 01~
~C K X X X X X X X X XX ¦ E
dP oP d~ d~ dQ dP dP dP ~P dP d? d~ I I :~
O o o ~ ~ ~ ~ ~ O O oO ~ ,-1 ~ Z - ' ' ' t~ ~ ~ ~ ~ r~ t~ r~ ~ ~~ I
l 8 ~ o ~ o o O N C) ul O O N I N
r ~
1 ` C PE~ o~
~ 1 ¦_ _ _ _ _ _ _ _ _ _~. _ ~ O ~
a ~ ~ ~ ~ ~ a~ e ~ a ~ ~ oJ r7 7 ~
O I_ _ __ _ _ _ __ _ _ _ ~ ~ O ~ O ~ t t4 l ~C O r~ ~ ~0 i I I .'~
= ~a~ L N __ __ __ _C _ __ V~
X U ' ' ','' ' ''~
W ~{~t~2~11 2 ~ PCT/U~92/0~3~7 Example~ 1-3 demon~trate the ef~ect of irradiation do~age and it~ effect on the cro~linking of PVP. Increasing irradiation do~aye increa~es the vi3c08ity ~nd cohe~ivene~s of the adhe~ive composition, all other compositional parameters remaining S const~nt.
~xamples 4-6 demon~trate the difference~ in adhesive composition properties based on variation of the mixture of plasticizer~ A~ the weight percentage of water increa~es, the visco~ity and cohesiveness of the adhesive decrea~e~, balan~ed by a decrease in adhe~iveness.
Example 7 and Compari~on Example 8 compare th~ effect of irradiation a~cording to the prOcQss of th~ pre~ent invention. All other parameters being constant, the ab~ence of irradiation of linear PVP fail to achieve adhesive properties required for the lS pre~ent invention. ~urther, a comparison of Example 7 with Example
6 shows acceptable adhe~ive properties within an irradiation dosage betw~en lO0 and 200 kGys (10-20 mrads).
Examples 9-12 differ from Examples 1-7 in that irradiation i9 provided by gamma hlgh enexgy sources and the plasticizer is limited to glycerin. A compari~on o~ Examples 9-12 shows decreasing presence of residue with increa~ing irradiation dosage balanced by a lo~ o~ some adhlesivene~s.
~xample 13 lO0 grams of ~olid PVP (~-90 from BASF and of 10 ~m particle size) were placed under nitrogen according to the following method. Samples, lO0 qrams each of ~olid PV~, were placed in 250 ml high density polyethy}ene bottle a~ailable from Nalgene and then plaoe in a vacuum oven at a~bient temperature. The vacuum o~en was e~acuated with a mechanical pump then filled with nitrogen until atmospheric pres~ure was obtained and thi~ ~roce~ was repeated S
times ~or each sample at which time the bottle containing the ~ample~ wa~ capped. While ~aled in the nitrogen atmosphere, each ~ample waB subjected to gamma irradiation of 150 kGy~ a~cording to the procedures of Example l.
Example 14 A co~tainer was charged with 75 gram~ of water, 16.25 i gram~ of polyethylene glycol (MM 300) and G.5 gram~ of XCl~and mixed until di~solution~ Then 8.5 ~r~m9 of 801id~ crosslinked PYP prepared according to the method o~ Example 13 ~-90 from BA5F, cro~linked with 150 kGy~ of gamma~radLation) waB added and the re~ultant compo~ition wa~ mixed in a blendar until it was homoyeneou~ The adhe~ive composit~on was coat~d at ~ive different thickne~se~ onto a 5.1 cm cent~r ~trip of an 8.9 cm polyeater ~ackin~, Llver coated with El700 ~ilver ink from Ercon, Inc. of WaLtham, M~. The coated -19- , w~ f l~znl P~r/U~i~2/~3~7 2 1 161 2 3 ~tripn w~re ~rl~ in an oven at 65C for 15 minutes. One 8et of ~ample~ of five differing caliper~ 2.54 cm x 4.44 cm having an adhesiv~ ar~a of 2.54 cm x 2.54 cm, was placed on each of six human paneli3ts and adhe~ion to ~kin was mea0ured a~ follows. Each ~ample wa~ applied to th~ back of a human ~ubject and rolled with a 2 kg roller to in~ure uniform application. Each sample was removed using a mechanical pulling device, con~isting of a motor driven ~crew drive which pu118 a 11.4 kg test line to which iB attached a 2.54 cm wide metal clip. The metal clip i~ attached to each electrode sample at its 2~54 cm width during pulling te~ting. Electrode~ were pulled in a plane parallel (180) to the back at a rate of 13-14 cm/min. The adhe~ion data are reported in grams/2.54 cm and r~nged ~rom 24 gr~m~/2.54 cm to 117 grams/2.54 cm. The caliper thickne~ses varl~d from 0.25 mm to 1.27 mm wet and from 0.05 mm to 0.36 dry.
The average~ of results are shown in Table II.
Table II
Example Wet Caliper Dry Caliper Skin Adhesion mm mm g/2.54cm 14a 0.25 0.050 24 14b 0.51 0.127 47 14c 0.76 0.178 62 14d 1.02 0.254 87 14e 1.27 0.~56 117 ~5 Example 15 A non-relea~e polyethylene terephthalate backing coated with silver ink (from Ercon, Inc., Waltham, ~) wa3 coated at 0.76 -~
mm with an adheQive compo~ition of the preaent inventioa havin~ 65 wt. percent water, 2 wt. per~ent potassium chloride and 35 wt.
percent solid PVP (X-90 from BAS~, crosslinked with 160 kGy~ gamma radiation). Electrodes were prepar~d to the dimensio~s of 2.54 cm x 2.54 cm and then placed back to back. The following electrical da~a ~-~
was mea3ured for the~e electrode on an Xtratek ET-65A ECG electrode te3ter from Xtratek of L~nexat Ran~as u~ing A3sociation for the Advancement of ~edical Instrumentation (AAMI) approved procedure3 for mea~uring direct current offset and adhe~ive-adhesive impedance. ~ ;~
.C. off~et wa~ 2.2 mV and A.C. impedance was 26 ohm~
(3~ 01 211 S 12 3 Pcr/US92~û~397 ,E~,~E~
To 50.0 grams of water was added 16.5 grams of pla~ticizer (PEG 300 from BASF) and 8.5 grams of ~olid PVP
~cros~linked with 160 kGys of gamma radiation under a nitrogen atmosphere a~ described in Example 13). The mixture was stirred on a mixsr for 10 minutes and then equilibrated for 24 hourq. Then 13.29 grams of this mixture wa~ loaded with 40 microliters of an ethanol ~olution containing 1 mci E~tradiol per milliliter of ethanol ~E~tradiol, tritium labeled, being obtained from NEN
Re~earch Products of BostGn MA). The r~ulting ~uspension wa~ then hand ~pread onto a polyethylena terephthalate ~ubstrate and then set in the hood open face to air dry for 1 we~k. One week later, 4 ~amples were prepared incorporating the air dried adheRive. Each sample was adhered to the stratum corneum ~ide of a piece of excised mou~e skin. Each of these sampl2s were then placed into a Valia Chien glass d.i~fu~ion cell (a3 de~cribed in "Drug Dev~lopment and Industrial Pharmacy lg85 No. 11, p. 1195 ~, ~uch that the receiver cell was in contact with the ~ubcutaneou0 ti~ue of the mou~e ~kln.
The area of expo~ed mous~ skin was 0.67 cm2. The t~mp*rature of the cell was 32C and the receiver cell ~olution was stirred at 600 rpm.
The counts per minute ~cpm) were mea~ured at 17, 19, 22 and 24 hours u~ing a Packard TRI-carb 460 CD Liquid Scintillation Counter. Four control ~amples were pr~pared to det~rmine the cpm/mL of sample.
~mploying a den~ity of 1.0 gram/mL ~or the dried adhe~ive, an avQrag~ loading was determined to be 2.3 x 166 cpm/mL. The average permeability of Estradiol was then determined to be 4.6 + 0.6 x lO-5 cm/hour with ~ lag time of lO hour~.
Example 17 and~Compa~rative Example 18 Two samples of solid PVP ~R-30 from BASF), one non-cro~ilinked and the other gamma irradiated at 150 kGy~ were extracted with acetone for 24 hours. Th~ acetone-soluble extract of each ~ample was analyzed u3ing a ~P 5B90 ga~ chromatograph from Hewlett Packard with an autosampler and a HP 3396 inte~rator from Hawlett Packard incorpor~ting a 15m DB~5 fused ~ilica capillary, 0.~5 mm ID, 0.25 micron fllm column. In both sample~ no detectable ~mount o N~vinyl-2-pyrrolidone wa~ ob~erY~d. Thu~, irradiation of ~olid PVP did not produce detectable amounts of monomexic unitR.
Cro~slinking of 301id PVP doe~ not yield detectable amsunt of fragment~ from commercially available PVP homopolymer.
xamples 19-32 and Comparative ~xamples 33-40 The follow~ng example~ were u~ed to di~cern the effe~t of variou~ pre-conditiQn~ on solid PVP powders administered prior to yamma irradiation. Physical properties mea8ured included Swellin~
.~
~2 1 - `
, . ~..':`
. . .
,:;
f1()~ PC~ $~0~397 2~1 6123 Capac1ty S ~ml~ of wa~er ab~orbed/gm of PVP).
100 g samples of solid PvP ~K-90 from BASF in a 10 ~m ~lze) were placed in 250 ml high den~ity polyethylene bottle~
available from Nalgene. The ~ample~ were divided into 4 set~ of pre-condition~.
No conditioning: u~ed as received;
Pre-dry: samples dried overnight at 50CC and 28 inches of Hg (711 Torr);
Purged: 8ample~ were placed in a vacuum ovan at ambient temp~rature and the vacuum oven wa~ evacuated with a mechanical pump, then filled with nitrogen until atmospheric pre~sure was obtained. This proce~0 was repeated three times prior to capping;
Pre-dry and Nitrogen Gas Purged: Bampl~B pre-dried a~
described in the ~econd condition and nitrogen gas purged as ~.
described in the third condition.
Twel~e sample~ covered the four pre-conditions and three g~mma dose ranges: 125 kGys; 150 kGys; and 200 kGys were ~tudied a8 Examples 19-30.
Example 31 di~fered from Example 25 in that K-9Q flakes le~s than about 250 micrometers in ~ize were used. Example 32 differed fxom Ex~mple 27 in that ~-90 flakes less than about 250 -~
micxometers in ~i~e were uAed. Comparative ~xample 33 wa~ prepared u~ing a chemical cro~linking agent diallyl maleate (DAM) according to the method discloeQd in ~xample 2 of U.S. Pat. No. 4,931,282 (Asmu~ et al.), exc~pt that 0.08 parts DAM substituted for 0.16 parts of 3,3'-ethylene-bi~-N-vinyl-2-pyrrolidone (EBYP). The ~-particle size waB le8~ than about 300 mi~rometer~ in 8ize.
The PVP ~ample~ of Example~ 19-32 and Comparative Example 33 were weighed into 20 ml gla~ vial~. Distilled wa~er was added to bring the mixture to 1% polymer ~olid~. The sample~ were ~ -~
allowsd 1 day to ~well and were mixed with a ~patula. Following ~ ^
another day, ~he ~amples were a~ain mixed with a ~patula and allowed t~ equilibrate for 2 weeks. The total height and~gel height in the vial wa~ mea~ured in cm. Equatlon I above was u~ed to ealculate ;~
Swelling Capacity. Table III report~ the re~ults.
: ~. ;., ' ,,~.
~'.'.' ~.
~,-" :--22- :;
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, : ~
. .
WC) ~ 020~ PCr/USg~/093g7 = ~. ,~ = = = == = rl l ~ U ,~ C, I ~n r N OD ~D O ~ ~ ~D r~) ~D ~D
11 =~ I~ Iulul ..,1 l ~ I t~l t~ C~l N ~1 ~:t N N d' r1 ~ r~ rl ~r r~ ¦
l _ ___ _ _ _ _ __ _ _ _ _ l 1~ I ~q ~I ~ . . ~ ~I tr~ . C~ . ~ N ~1 .
s~ N ~7 ~r~ ~r) ~ ~t~ 1~ ~) t~) l .,.---- -- - - .-- -- .--. - ---l l 1~1 3 3¦ ~ ~r N r1 r1 r1 ~ r1 10 rt -1 It) r1 N r1 ¦
l 1~1 ~ __ _ _ _ _ __ _ _ _I
3 ¦ r ¦ ~ ¦ 1~ ¦ N ul ~ U~ N ¦ 1`7 ¦ ¦ N ~
_ N ---- N ------ N ----1 .:
Il ~ 11 ol a' I ~1 4 C¦ ol d ~ cl ~ o I Z ~ s ~ ~; ~ ~ ~ ;5 ~ Z ,,~ Z Z ~ ~ ~
I j ~ ~ I ~ ~ ~ ~ o o ~ o o g o o o o ~ ~1 ¦ ~ 8 ~ 1 ~ --~ ~ --~ --~ ~1 ~ ~ N ~ ~I ~1 ~ U ~> ¦ :;
I _ _ _ _ _ ~LL I'' -23~
~V~ 3~11 rcr/v~2~ 97 211 S 12 3 In the Errede paper described above, the relation~hip between polymer swelling S in a given liquid i~ descxibed a~ a function of the average number of backbone car~on atoms in polymer ~egments between crosslinked junction~, A, according to Equation II
above.
European Patent Publication 0 322 098 ~Duan) and U.S.
Pat. No. 4,931,282 (A~mu~ et al.) identi~ied u~eful chemical cro~linkers for cro~slinking N-vinyl~2-pyrrolidone, in order ~o provide u~eful adhesive properties. One useful chemical cro~linking agent was EBVP. By plotting Al/3 v~ S for the E8VP
crosslinked syatsm polymerized using method according to examples from U.S. Pat. No. 4,931,282, relative crosslinking of radiation processing according to the present invention to a conventional chemical approach can be compared.
This comparison doe~ not provide an absolute de~cription of the cxo~slinked nature of the gamma irradiated polymer but rather provides an under~tanding that solid radiation-cro~slinked PVP
powders o~ the present invention act as though they are "very lightly" crosslinked. Table IV provides comparativs EBVP data, mea~uring 1/~, which i8 cro~slink dan~ity, and Al/3 to compute ~welling Capacity, S. Fig. 5 plot~ Al/3 and Swelling Capacity to provide additional analy~is.
~24-W~ ~3~ 12 i 1612 3 PC~r/US~/0~3~7 r ~ = = ~ = = I
I ~1 ~ # I
l 3~D~1 'I ~ ~r r~ r-~ ~_1 I
l . .~ _ , , _ _ :.
I 5~ ¦ r~ r o 0 0 u, o ¦ . ..
l 'C N ~` ~r _I 0 1~ ~
I __ _ _-- - - I
l ~ ~ ~ lo 9`~ ~ ~o ~ol : ~
l ~ It ~ le X * lt ~ l '~' I o~ ~ a~) ~D d' ~D u~l , ...
l ~ OD ~i r~ 1` -~ ~ U~ I
~ r r~ Tl 1~ l 3 ~ ~ ~ o, o o I o ~ o~
1~ __ __ --1 ' ~ ~ ~ ~ ~ a p ~ ~ : ~; : :~
I C _ _ _ _ _ _ ~ :~ ~ ~ ~ ~ t~ ~ ~ ~ ~ O ; ~
_--= === == _ ~-c ~ #
-25~
..
W Q ~?~JI~ pCT/US9~/09397 ~1 l 612 3 By compari~on the S values oP the swollen radiation-cro~linked PVP in Example~ 19-32 rang~d from 44-82 which according to correlation with data from Table :rv and Fig. 5, c~mpare~ to an Esvp crosslinked PVP gels having a 1/~ from about 5.7 ~ 10-3 to about 9 * 10-5. In fact EBVP cro~slinked PVP gel~ under the~e bulk pol~mer~zation conditions do not form in~oluble gels at the lower concentrations. See Comparative ~xamples 34 and 35. Thus, radiation crosslinking of solid PVP i~ a preferred method to provide a ~wellable PVP pre~sure-sensitive adhesive compo0ition. ~ ~
Examples 41-52~ e~ e~ 3 Radiation-cro~slinked PVP powders prepared according to Example~ 19-30 were formulated into the following adhesive -~
compo~ition of 4.0 gram3 of solid, radiation-cro~31inked PVP; 0.25 ~rams of ethyl acetate used to reduce agglomeration of the powder during mixing with water; 9.3 grams of glycerol; and 66.45 grams of deionized water. The compo~ition wa~ coated on aluminum foil at a wet coating thicknes~ of 0.38 mm, dried in an oven at 79C for 15 minute~ and laminated to another ~trip of aluminum foil. T-peel adhosion tests according to ASTM method D1876 were determined on 2.54 cm wide aample~ drawn apart on an Instron te~ter with a Jaw Speed o~ 25.4 cm/min.
For compari~on, DAM chemically cros~linked PVP was prepared according to the method of Example 2 of U.5. Pat. No.
4,931,282, except that 0.08 p~rt~ D~M sub3tituted for 0.16 parts EBVP. A compo~ition was prepared o 4.0 gr2ms DAM crosalinked PVP;
0.25 gram3 of ethyl acetate; 9.3 grams of glycerol; and 66.4S grams o~ deionized water. The compo~ition was test~d by the ~ame procedure for Examples 41-52, except that it had a wet coating thickne~ of D.30 mm on aluminum foil.
The results axe reported in Table V. ;~
''','';
-~6~
YV~ ~i0~0I PC~/VS~2/0~7 r ~v I I a~a I I T-Poel Alu~lnw-t Foil ¦ ;~xaDI~leDo~ Pre-Conditil~n~v~r~ge of 5 Test~) (gra~3/2 . 54 c~) I .: . ~ _ _ ~ .................. . __ 1 41 125 None 109 ¦
I . . .------------I
42 125 Pre-~ry 82 __ .. . 1 ¦ 43 125 N2 Purge 95 . -1l ¦ 44 125 Purge 77 ¦ .
I ._ _ . _ , ,... ___ ¦ _ 45 150 None 86 -:;
1 46 150 Pre-Dr 91 . _ ~ . _ - ~
47 150 N2 Purge 97 . _ 48 150 Pre-Dry & N2 86 Purae _, _ _ _ , _ __ ..
49 200 None 77 . . __, ,... ...___ 200 Pre-Dry 73 __-. __ ~ ..
51 200 N2 Purge 77 _ _ _ ~_ ,~_ ~"~_ . . ~
52 200 Pre Dry & N2 54 Purae _ ,_ _~ ._ _. .
53 X-linked None 54 with _ ._ 0.08% DAM _ _ = ~ .
:
The results indicate that increased radiation dose reduces the sels' adhe~ive performance. The data also ~ugge~t that the combination of pre-drying and nitrogen gas purging increa~es the efficiency of crosslinking a8 i8 indicated by the lower adheqive per~ormance at equivalent gamma dosage. A11 samples compare very :~
favora~ly to Comparative Example 53 of DAM cro~linked PVP by .m providing higher adhesion while maintaining cohe~iveness.
Without being lîmited to the foregoing, the invention is hereby claimed.
~"
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';,~,''"' ... .
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Examples 9-12 differ from Examples 1-7 in that irradiation i9 provided by gamma hlgh enexgy sources and the plasticizer is limited to glycerin. A compari~on o~ Examples 9-12 shows decreasing presence of residue with increa~ing irradiation dosage balanced by a lo~ o~ some adhlesivene~s.
~xample 13 lO0 grams of ~olid PVP (~-90 from BASF and of 10 ~m particle size) were placed under nitrogen according to the following method. Samples, lO0 qrams each of ~olid PV~, were placed in 250 ml high density polyethy}ene bottle a~ailable from Nalgene and then plaoe in a vacuum oven at a~bient temperature. The vacuum o~en was e~acuated with a mechanical pump then filled with nitrogen until atmospheric pres~ure was obtained and thi~ ~roce~ was repeated S
times ~or each sample at which time the bottle containing the ~ample~ wa~ capped. While ~aled in the nitrogen atmosphere, each ~ample waB subjected to gamma irradiation of 150 kGy~ a~cording to the procedures of Example l.
Example 14 A co~tainer was charged with 75 gram~ of water, 16.25 i gram~ of polyethylene glycol (MM 300) and G.5 gram~ of XCl~and mixed until di~solution~ Then 8.5 ~r~m9 of 801id~ crosslinked PYP prepared according to the method o~ Example 13 ~-90 from BA5F, cro~linked with 150 kGy~ of gamma~radLation) waB added and the re~ultant compo~ition wa~ mixed in a blendar until it was homoyeneou~ The adhe~ive composit~on was coat~d at ~ive different thickne~se~ onto a 5.1 cm cent~r ~trip of an 8.9 cm polyeater ~ackin~, Llver coated with El700 ~ilver ink from Ercon, Inc. of WaLtham, M~. The coated -19- , w~ f l~znl P~r/U~i~2/~3~7 2 1 161 2 3 ~tripn w~re ~rl~ in an oven at 65C for 15 minutes. One 8et of ~ample~ of five differing caliper~ 2.54 cm x 4.44 cm having an adhesiv~ ar~a of 2.54 cm x 2.54 cm, was placed on each of six human paneli3ts and adhe~ion to ~kin was mea0ured a~ follows. Each ~ample wa~ applied to th~ back of a human ~ubject and rolled with a 2 kg roller to in~ure uniform application. Each sample was removed using a mechanical pulling device, con~isting of a motor driven ~crew drive which pu118 a 11.4 kg test line to which iB attached a 2.54 cm wide metal clip. The metal clip i~ attached to each electrode sample at its 2~54 cm width during pulling te~ting. Electrode~ were pulled in a plane parallel (180) to the back at a rate of 13-14 cm/min. The adhe~ion data are reported in grams/2.54 cm and r~nged ~rom 24 gr~m~/2.54 cm to 117 grams/2.54 cm. The caliper thickne~ses varl~d from 0.25 mm to 1.27 mm wet and from 0.05 mm to 0.36 dry.
The average~ of results are shown in Table II.
Table II
Example Wet Caliper Dry Caliper Skin Adhesion mm mm g/2.54cm 14a 0.25 0.050 24 14b 0.51 0.127 47 14c 0.76 0.178 62 14d 1.02 0.254 87 14e 1.27 0.~56 117 ~5 Example 15 A non-relea~e polyethylene terephthalate backing coated with silver ink (from Ercon, Inc., Waltham, ~) wa3 coated at 0.76 -~
mm with an adheQive compo~ition of the preaent inventioa havin~ 65 wt. percent water, 2 wt. per~ent potassium chloride and 35 wt.
percent solid PVP (X-90 from BAS~, crosslinked with 160 kGy~ gamma radiation). Electrodes were prepar~d to the dimensio~s of 2.54 cm x 2.54 cm and then placed back to back. The following electrical da~a ~-~
was mea3ured for the~e electrode on an Xtratek ET-65A ECG electrode te3ter from Xtratek of L~nexat Ran~as u~ing A3sociation for the Advancement of ~edical Instrumentation (AAMI) approved procedure3 for mea~uring direct current offset and adhe~ive-adhesive impedance. ~ ;~
.C. off~et wa~ 2.2 mV and A.C. impedance was 26 ohm~
(3~ 01 211 S 12 3 Pcr/US92~û~397 ,E~,~E~
To 50.0 grams of water was added 16.5 grams of pla~ticizer (PEG 300 from BASF) and 8.5 grams of ~olid PVP
~cros~linked with 160 kGys of gamma radiation under a nitrogen atmosphere a~ described in Example 13). The mixture was stirred on a mixsr for 10 minutes and then equilibrated for 24 hourq. Then 13.29 grams of this mixture wa~ loaded with 40 microliters of an ethanol ~olution containing 1 mci E~tradiol per milliliter of ethanol ~E~tradiol, tritium labeled, being obtained from NEN
Re~earch Products of BostGn MA). The r~ulting ~uspension wa~ then hand ~pread onto a polyethylena terephthalate ~ubstrate and then set in the hood open face to air dry for 1 we~k. One week later, 4 ~amples were prepared incorporating the air dried adheRive. Each sample was adhered to the stratum corneum ~ide of a piece of excised mou~e skin. Each of these sampl2s were then placed into a Valia Chien glass d.i~fu~ion cell (a3 de~cribed in "Drug Dev~lopment and Industrial Pharmacy lg85 No. 11, p. 1195 ~, ~uch that the receiver cell was in contact with the ~ubcutaneou0 ti~ue of the mou~e ~kln.
The area of expo~ed mous~ skin was 0.67 cm2. The t~mp*rature of the cell was 32C and the receiver cell ~olution was stirred at 600 rpm.
The counts per minute ~cpm) were mea~ured at 17, 19, 22 and 24 hours u~ing a Packard TRI-carb 460 CD Liquid Scintillation Counter. Four control ~amples were pr~pared to det~rmine the cpm/mL of sample.
~mploying a den~ity of 1.0 gram/mL ~or the dried adhe~ive, an avQrag~ loading was determined to be 2.3 x 166 cpm/mL. The average permeability of Estradiol was then determined to be 4.6 + 0.6 x lO-5 cm/hour with ~ lag time of lO hour~.
Example 17 and~Compa~rative Example 18 Two samples of solid PVP ~R-30 from BASF), one non-cro~ilinked and the other gamma irradiated at 150 kGy~ were extracted with acetone for 24 hours. Th~ acetone-soluble extract of each ~ample was analyzed u3ing a ~P 5B90 ga~ chromatograph from Hewlett Packard with an autosampler and a HP 3396 inte~rator from Hawlett Packard incorpor~ting a 15m DB~5 fused ~ilica capillary, 0.~5 mm ID, 0.25 micron fllm column. In both sample~ no detectable ~mount o N~vinyl-2-pyrrolidone wa~ ob~erY~d. Thu~, irradiation of ~olid PVP did not produce detectable amounts of monomexic unitR.
Cro~slinking of 301id PVP doe~ not yield detectable amsunt of fragment~ from commercially available PVP homopolymer.
xamples 19-32 and Comparative ~xamples 33-40 The follow~ng example~ were u~ed to di~cern the effe~t of variou~ pre-conditiQn~ on solid PVP powders administered prior to yamma irradiation. Physical properties mea8ured included Swellin~
.~
~2 1 - `
, . ~..':`
. . .
,:;
f1()~ PC~ $~0~397 2~1 6123 Capac1ty S ~ml~ of wa~er ab~orbed/gm of PVP).
100 g samples of solid PvP ~K-90 from BASF in a 10 ~m ~lze) were placed in 250 ml high den~ity polyethylene bottle~
available from Nalgene. The ~ample~ were divided into 4 set~ of pre-condition~.
No conditioning: u~ed as received;
Pre-dry: samples dried overnight at 50CC and 28 inches of Hg (711 Torr);
Purged: 8ample~ were placed in a vacuum ovan at ambient temp~rature and the vacuum oven wa~ evacuated with a mechanical pump, then filled with nitrogen until atmospheric pre~sure was obtained. This proce~0 was repeated three times prior to capping;
Pre-dry and Nitrogen Gas Purged: Bampl~B pre-dried a~
described in the ~econd condition and nitrogen gas purged as ~.
described in the third condition.
Twel~e sample~ covered the four pre-conditions and three g~mma dose ranges: 125 kGys; 150 kGys; and 200 kGys were ~tudied a8 Examples 19-30.
Example 31 di~fered from Example 25 in that K-9Q flakes le~s than about 250 micrometers in ~ize were used. Example 32 differed fxom Ex~mple 27 in that ~-90 flakes less than about 250 -~
micxometers in ~i~e were uAed. Comparative ~xample 33 wa~ prepared u~ing a chemical cro~linking agent diallyl maleate (DAM) according to the method discloeQd in ~xample 2 of U.S. Pat. No. 4,931,282 (Asmu~ et al.), exc~pt that 0.08 parts DAM substituted for 0.16 parts of 3,3'-ethylene-bi~-N-vinyl-2-pyrrolidone (EBYP). The ~-particle size waB le8~ than about 300 mi~rometer~ in 8ize.
The PVP ~ample~ of Example~ 19-32 and Comparative Example 33 were weighed into 20 ml gla~ vial~. Distilled wa~er was added to bring the mixture to 1% polymer ~olid~. The sample~ were ~ -~
allowsd 1 day to ~well and were mixed with a ~patula. Following ~ ^
another day, ~he ~amples were a~ain mixed with a ~patula and allowed t~ equilibrate for 2 weeks. The total height and~gel height in the vial wa~ mea~ured in cm. Equatlon I above was u~ed to ealculate ;~
Swelling Capacity. Table III report~ the re~ults.
: ~. ;., ' ,,~.
~'.'.' ~.
~,-" :--22- :;
~,`.
.`, ~
, : ~
. .
WC) ~ 020~ PCr/USg~/093g7 = ~. ,~ = = = == = rl l ~ U ,~ C, I ~n r N OD ~D O ~ ~ ~D r~) ~D ~D
11 =~ I~ Iulul ..,1 l ~ I t~l t~ C~l N ~1 ~:t N N d' r1 ~ r~ rl ~r r~ ¦
l _ ___ _ _ _ _ __ _ _ _ _ l 1~ I ~q ~I ~ . . ~ ~I tr~ . C~ . ~ N ~1 .
s~ N ~7 ~r~ ~r) ~ ~t~ 1~ ~) t~) l .,.---- -- - - .-- -- .--. - ---l l 1~1 3 3¦ ~ ~r N r1 r1 r1 ~ r1 10 rt -1 It) r1 N r1 ¦
l 1~1 ~ __ _ _ _ _ __ _ _ _I
3 ¦ r ¦ ~ ¦ 1~ ¦ N ul ~ U~ N ¦ 1`7 ¦ ¦ N ~
_ N ---- N ------ N ----1 .:
Il ~ 11 ol a' I ~1 4 C¦ ol d ~ cl ~ o I Z ~ s ~ ~; ~ ~ ~ ;5 ~ Z ,,~ Z Z ~ ~ ~
I j ~ ~ I ~ ~ ~ ~ o o ~ o o g o o o o ~ ~1 ¦ ~ 8 ~ 1 ~ --~ ~ --~ --~ ~1 ~ ~ N ~ ~I ~1 ~ U ~> ¦ :;
I _ _ _ _ _ ~LL I'' -23~
~V~ 3~11 rcr/v~2~ 97 211 S 12 3 In the Errede paper described above, the relation~hip between polymer swelling S in a given liquid i~ descxibed a~ a function of the average number of backbone car~on atoms in polymer ~egments between crosslinked junction~, A, according to Equation II
above.
European Patent Publication 0 322 098 ~Duan) and U.S.
Pat. No. 4,931,282 (A~mu~ et al.) identi~ied u~eful chemical cro~linkers for cro~slinking N-vinyl~2-pyrrolidone, in order ~o provide u~eful adhesive properties. One useful chemical cro~linking agent was EBVP. By plotting Al/3 v~ S for the E8VP
crosslinked syatsm polymerized using method according to examples from U.S. Pat. No. 4,931,282, relative crosslinking of radiation processing according to the present invention to a conventional chemical approach can be compared.
This comparison doe~ not provide an absolute de~cription of the cxo~slinked nature of the gamma irradiated polymer but rather provides an under~tanding that solid radiation-cro~slinked PVP
powders o~ the present invention act as though they are "very lightly" crosslinked. Table IV provides comparativs EBVP data, mea~uring 1/~, which i8 cro~slink dan~ity, and Al/3 to compute ~welling Capacity, S. Fig. 5 plot~ Al/3 and Swelling Capacity to provide additional analy~is.
~24-W~ ~3~ 12 i 1612 3 PC~r/US~/0~3~7 r ~ = = ~ = = I
I ~1 ~ # I
l 3~D~1 'I ~ ~r r~ r-~ ~_1 I
l . .~ _ , , _ _ :.
I 5~ ¦ r~ r o 0 0 u, o ¦ . ..
l 'C N ~` ~r _I 0 1~ ~
I __ _ _-- - - I
l ~ ~ ~ lo 9`~ ~ ~o ~ol : ~
l ~ It ~ le X * lt ~ l '~' I o~ ~ a~) ~D d' ~D u~l , ...
l ~ OD ~i r~ 1` -~ ~ U~ I
~ r r~ Tl 1~ l 3 ~ ~ ~ o, o o I o ~ o~
1~ __ __ --1 ' ~ ~ ~ ~ ~ a p ~ ~ : ~; : :~
I C _ _ _ _ _ _ ~ :~ ~ ~ ~ ~ t~ ~ ~ ~ ~ O ; ~
_--= === == _ ~-c ~ #
-25~
..
W Q ~?~JI~ pCT/US9~/09397 ~1 l 612 3 By compari~on the S values oP the swollen radiation-cro~linked PVP in Example~ 19-32 rang~d from 44-82 which according to correlation with data from Table :rv and Fig. 5, c~mpare~ to an Esvp crosslinked PVP gels having a 1/~ from about 5.7 ~ 10-3 to about 9 * 10-5. In fact EBVP cro~slinked PVP gel~ under the~e bulk pol~mer~zation conditions do not form in~oluble gels at the lower concentrations. See Comparative ~xamples 34 and 35. Thus, radiation crosslinking of solid PVP i~ a preferred method to provide a ~wellable PVP pre~sure-sensitive adhesive compo0ition. ~ ~
Examples 41-52~ e~ e~ 3 Radiation-cro~slinked PVP powders prepared according to Example~ 19-30 were formulated into the following adhesive -~
compo~ition of 4.0 gram3 of solid, radiation-cro~31inked PVP; 0.25 ~rams of ethyl acetate used to reduce agglomeration of the powder during mixing with water; 9.3 grams of glycerol; and 66.45 grams of deionized water. The compo~ition wa~ coated on aluminum foil at a wet coating thicknes~ of 0.38 mm, dried in an oven at 79C for 15 minute~ and laminated to another ~trip of aluminum foil. T-peel adhosion tests according to ASTM method D1876 were determined on 2.54 cm wide aample~ drawn apart on an Instron te~ter with a Jaw Speed o~ 25.4 cm/min.
For compari~on, DAM chemically cros~linked PVP was prepared according to the method of Example 2 of U.5. Pat. No.
4,931,282, except that 0.08 p~rt~ D~M sub3tituted for 0.16 parts EBVP. A compo~ition was prepared o 4.0 gr2ms DAM crosalinked PVP;
0.25 gram3 of ethyl acetate; 9.3 grams of glycerol; and 66.4S grams o~ deionized water. The compo~ition was test~d by the ~ame procedure for Examples 41-52, except that it had a wet coating thickne~ of D.30 mm on aluminum foil.
The results axe reported in Table V. ;~
''','';
-~6~
YV~ ~i0~0I PC~/VS~2/0~7 r ~v I I a~a I I T-Poel Alu~lnw-t Foil ¦ ;~xaDI~leDo~ Pre-Conditil~n~v~r~ge of 5 Test~) (gra~3/2 . 54 c~) I .: . ~ _ _ ~ .................. . __ 1 41 125 None 109 ¦
I . . .------------I
42 125 Pre-~ry 82 __ .. . 1 ¦ 43 125 N2 Purge 95 . -1l ¦ 44 125 Purge 77 ¦ .
I ._ _ . _ , ,... ___ ¦ _ 45 150 None 86 -:;
1 46 150 Pre-Dr 91 . _ ~ . _ - ~
47 150 N2 Purge 97 . _ 48 150 Pre-Dry & N2 86 Purae _, _ _ _ , _ __ ..
49 200 None 77 . . __, ,... ...___ 200 Pre-Dry 73 __-. __ ~ ..
51 200 N2 Purge 77 _ _ _ ~_ ,~_ ~"~_ . . ~
52 200 Pre Dry & N2 54 Purae _ ,_ _~ ._ _. .
53 X-linked None 54 with _ ._ 0.08% DAM _ _ = ~ .
:
The results indicate that increased radiation dose reduces the sels' adhe~ive performance. The data also ~ugge~t that the combination of pre-drying and nitrogen gas purging increa~es the efficiency of crosslinking a8 i8 indicated by the lower adheqive per~ormance at equivalent gamma dosage. A11 samples compare very :~
favora~ly to Comparative Example 53 of DAM cro~linked PVP by .m providing higher adhesion while maintaining cohe~iveness.
Without being lîmited to the foregoing, the invention is hereby claimed.
~"
,' '': ' ' ':, ,~, ~, .',:,~',~' -27~~
';,~,''"' ... .
'"'. '~'-
Claims (12)
1. A hydrophilic, pressure-sensitive adhesive composition comprising: poly(N-vinyl lactam) radiation-crosslinked while in a solid form and an essentially unirradiated plasticizer present in an amount sufficient to form a cohesive pressure-sensitive adhesive composition.
2. A biomedical electrode (10) comprising; a field (14) of adhesive conductive medium of a composition according to Claim 1 for contacting mammalian skin and a means for electrical communication (16) for interfacing with the adhesive conductive medium and electrical diagnostic, therapeutic, or electrosurgical instrumentation, the adhesive conductive medium adhered to the means for electrical communication.
3. A mammalian skin covering (30) comprising: an adhesive layer (34) of composition according to Claim 1 for contacting mammalian skin and a backing layer (32), the adhesive layer adhered to the backing layer.
4. A pharmaceutical delivery device (40) comprising: an adhesive layer (44) of a composition according to Claim 1 for contacting mammalian skin and a backing layer (42), the adhesive layer adhered to the backing layer.
5. The composition according to Claim 1 or as used in the articles of Claims 2-4, wherein the amount of the essentially unirradiated plasticiear ranges from about 50 to about 90 weight percent of the composition.
6. The composition according to Claim 1 or as used in the articles of Claims 2-4, wherein the amount of essentially unirradiated plasticizer ranges from about 60 to about 80 weight percent of the composition, wherein the poly(N-vinyl lactam) is poly(N-vinyl pyrrolidone), and wherein the radiation-crosslinked poly(N-vinyl lactam) has a Swelling Capacity of at lest 15 milliliters of water per gram of the radiation-crosslinked poly (n-vinyl lactam.)
WO 93/10201 PCT/US92/09397 acetate, and 2-acrylamido-2-methyl-1-propane sulfonic acid or it8s salt; the copolymer comprising N-vinyl-2-pyrrolidone monomeric units in an amount no less than about 50 weight percent of the polyl N-vinyl lactam).
8. The composition according to Claim 1 or as used in the article of Claim 2, further comprising an electrolyte present in an amount of from about 0.5 to about 5 weight percent of the adhesive conductive medium, and wherein the means for electrical communication comprises a conductor member having an interface portion available for mechanical and electrical contact with the electrical diagnostic, therapeutic, or electrosurgical instrumentation.
9. The composition according to Claim 1 or as used in the article of Claim 3, wherein the composition in the adhesive layer comprises discrete swollen gel particles dispersed in a continuous pressure-sensitive adhesive matrix to form a two phase composite adhesive layer; and wherein the composition optionally comprises an antimicrobial agent.
10. The composition according to Claim 1 or as used in the article of Claim 4, further comprising a a topical, transdermal, or iontophoretic therapeutic agent or pharmaceutical and optionally further comprises an excipient, a solvent, or a penetration enhancing agent.
11. A method of preparing a hydrophilic, pressure-sensitive adhesive composition comprising steps of:
(a) irradiating non-crosslinked, solid poly(N-vinyl lactam) with ionizing radiation to crosslink the poly(N-vinyl lactam), (b) mixing the radiation-crosslinked poly(N-vinyl lactam) with an essentially unirradiated plasticizer in an amount sufficient to form a cohesive and pressure-sensitive adhesive composition, and optionally, (c) mixing an electrolyte, an antimicrobial agent, or a pharmaceutical into the composition, and optionally, (d) mixing the radiation-crosslinked poly(N-vinyl lactam), the essentially unirradiated plasticizer, and optional electrolyte, antimicrobial agent, or pharmaceutical into a solvent, and optionally, (e) casting the composition in solvent onto a substrate, and optionally, (f) evaporating solvent.
(a) irradiating non-crosslinked, solid poly(N-vinyl lactam) with ionizing radiation to crosslink the poly(N-vinyl lactam), (b) mixing the radiation-crosslinked poly(N-vinyl lactam) with an essentially unirradiated plasticizer in an amount sufficient to form a cohesive and pressure-sensitive adhesive composition, and optionally, (c) mixing an electrolyte, an antimicrobial agent, or a pharmaceutical into the composition, and optionally, (d) mixing the radiation-crosslinked poly(N-vinyl lactam), the essentially unirradiated plasticizer, and optional electrolyte, antimicrobial agent, or pharmaceutical into a solvent, and optionally, (e) casting the composition in solvent onto a substrate, and optionally, (f) evaporating solvent.
12. The method according to Claim 11, wherein the ionizing radiation comprises alpha, beta, gamma, electron-beam, or x-ray radiation, and wherein the ionizing radiation is irradiated in at least one dose cumulatively comprising from about 25 kGys. to about 400 kGys.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/792,442 | 1991-11-15 | ||
US07/792,442 US5276079A (en) | 1991-11-15 | 1991-11-15 | Pressure-sensitive poly(n-vinyl lactam) adhesive composition and method for producing and using same |
Publications (1)
Publication Number | Publication Date |
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CA2116123A1 true CA2116123A1 (en) | 1993-05-27 |
Family
ID=25156892
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Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002116123A Abandoned CA2116123A1 (en) | 1991-11-15 | 1992-10-30 | Pressure-sensitive poly(n-vinyl lactam) adhesive composition and method for producing and using same |
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US (4) | US5276079A (en) |
EP (1) | EP0612342B1 (en) |
JP (1) | JP3426231B2 (en) |
AT (1) | ATE146212T1 (en) |
AU (1) | AU657188B2 (en) |
CA (1) | CA2116123A1 (en) |
DE (1) | DE69215893T2 (en) |
DK (1) | DK0612342T3 (en) |
WO (1) | WO1993010201A1 (en) |
Families Citing this family (158)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU652494B2 (en) * | 1991-11-15 | 1994-08-25 | Minnesota Mining And Manufacturing Company | Solid state conductive polymer compositions, biomedical electrodes containing such compositions, and method of preparing same |
US5276079A (en) * | 1991-11-15 | 1994-01-04 | Minnesota Mining And Manufacturing Company | Pressure-sensitive poly(n-vinyl lactam) adhesive composition and method for producing and using same |
DE4238263A1 (en) * | 1991-11-15 | 1993-05-19 | Minnesota Mining & Mfg | Adhesive comprising hydrogel and crosslinked polyvinyl:lactam - is used in electrodes for biomedical application providing low impedance and good mechanical properties when water and/or moisture is absorbed from skin |
WO1993009713A1 (en) * | 1991-11-15 | 1993-05-27 | Minnesota Mining And Manufacturing Company | Biomedical electrode provided with two-phase composites conductive, pressure-sensitive adhesive |
US5622168A (en) * | 1992-11-18 | 1997-04-22 | John L. Essmyer | Conductive hydrogels and physiological electrodes and electrode assemblies therefrom |
US5496363A (en) * | 1993-06-02 | 1996-03-05 | Minnesota Mining And Manufacturing Company | Electrode and assembly |
US5650060A (en) * | 1994-01-28 | 1997-07-22 | Minnesota Mining And Manufacturing Company | Ionically conductive agent, system for cathodic protection of galvanically active metals, and method and apparatus for using same |
US5670557A (en) * | 1994-01-28 | 1997-09-23 | Minnesota Mining And Manufacturing Company | Polymerized microemulsion pressure sensitive adhesive compositions and methods of preparing and using same |
TW369558B (en) * | 1994-01-28 | 1999-09-11 | Minnesota Mining & Mfg | Polymerized microemulsion pressure sensitive adhesive compositions and methods of preparing and using same |
US5505200A (en) * | 1994-01-28 | 1996-04-09 | Minnesota Mining And Manufacturing | Biomedical conductor containing inorganic oxides and biomedical electrodes prepared therefrom |
EP0754064B1 (en) * | 1994-04-08 | 2003-05-28 | Atrix Laboratories, Inc. | An adjunctive polymer system for use with medical device |
EP0691124A1 (en) * | 1994-07-07 | 1996-01-10 | Sara Lee/DE N.V. | Mouth care products |
US5726250A (en) * | 1994-07-11 | 1998-03-10 | Adhesives Research, Inc. | Covalently crosslinked water-absorbent graft copolymer |
US5731387A (en) * | 1994-07-11 | 1998-03-24 | Adhesives Research, Inc. | Ionically-crosslinked water-absorbent graft copolymer |
ATE194281T1 (en) * | 1994-09-14 | 2000-07-15 | Minnesota Mining & Mfg | TRANSDERMAL ACTIVE RELEASE MATRIX |
CA2177042C (en) | 1994-09-21 | 2009-05-12 | Suong-Hyu Hyon | Ultra high molecular weight polyethylene molded article for artificial joints and method of preparing the same |
US5562653A (en) * | 1994-11-16 | 1996-10-08 | Hercules Incorporated | Medical devices composed of low ceiling temperature polymers |
US5702753A (en) * | 1994-11-22 | 1997-12-30 | Minnesota Mining And Manufacturing Company | Method of manufacturing a diagnostic electrode |
EP2322137A1 (en) | 1995-06-22 | 2011-05-18 | Minnesota Mining And Manufacturing Company | Stable hydroalcoholic compositions |
US6623744B2 (en) * | 1995-06-22 | 2003-09-23 | 3M Innovative Properties Company | Stable hydroalcoholic compositions |
US7566460B2 (en) * | 1995-06-22 | 2009-07-28 | 3M Innovative Properties Company | Stable hydroalcoholic compositions |
EP2314272A1 (en) * | 1995-06-22 | 2011-04-27 | Minnesota Mining And Manufacturing Company | Stable hydroalcoholic compositions |
FR2739030B1 (en) * | 1995-09-27 | 1997-11-21 | Lhd Lab Hygiene Dietetique | USE OF A COPOLYMER OF VINYL ACETATE AND N-VINYL-2-PYRROLIDONE IN A TRANSDERMAL MATRIX SYSTEM |
US5813981A (en) * | 1995-12-29 | 1998-09-29 | Minnesota Mining And Manufacturing Company | Tab style electrode |
US6121508A (en) * | 1995-12-29 | 2000-09-19 | 3M Innovative Properties Company | Polar, lipophilic pressure-sensitive adhesive compositions and medical devices using same |
EP1019105B1 (en) * | 1995-12-29 | 2002-09-04 | Minnesota Mining And Manufacturing Company | Polar, lipophilic pressure-sensitive adhesive compositions and medical devices using same |
US5827184A (en) * | 1995-12-29 | 1998-10-27 | Minnesota Mining And Manufacturing Company | Self-packaging bioelectrodes |
US6135953A (en) * | 1996-01-25 | 2000-10-24 | 3M Innovative Properties Company | Multi-functional biomedical electrodes |
US5846558A (en) * | 1996-03-19 | 1998-12-08 | Minnesota Mining And Manufacturing Company | Ionically conductive adhesives prepared from zwitterionic materials and medical devices using such adhesives |
US5836942A (en) * | 1996-04-04 | 1998-11-17 | Minnesota Mining And Manufacturing Company | Biomedical electrode with lossy dielectric properties |
WO1997041568A1 (en) * | 1996-04-29 | 1997-11-06 | Minnesota Mining And Manufacturing Company | Electrical conductor for biomedical electrodes and biomedical electrodes prepared therefrom |
US5797902A (en) * | 1996-05-10 | 1998-08-25 | Minnesota Mining And Manufacturing Company | Biomedical electrode providing early detection of accidental detachment |
US5947961A (en) * | 1996-05-10 | 1999-09-07 | Minnesota Mining And Manufacturing Company | Biomedical electrode having skin-equilibrating adhesive at its perimeter and method for using same |
US6190683B1 (en) * | 1996-09-03 | 2001-02-20 | Lintec Corporation | Blackhead-removing face pack sheet |
US6415170B1 (en) * | 1996-12-09 | 2002-07-02 | 3M Innovative Properties Company | Biomedical electrode and method for its manufacture |
EP0850649A1 (en) * | 1996-12-23 | 1998-07-01 | The Procter & Gamble Company | Adhesive for application of functional articles to the skin and comfortable removal of such articles |
US6211263B1 (en) | 1996-12-23 | 2001-04-03 | The Procter & Gamble Company | Adhesive for secure topical attachment to the skin and comfortable removal |
US6177482B1 (en) | 1996-12-23 | 2001-01-23 | The Proctor & Gamble Company | Adhesive for secure topical attachment to the skin and comfortable removal |
US6365645B1 (en) | 1996-12-23 | 2002-04-02 | The Procter & Gamble Co. | Adhesive for application of functional articles to the skin and comfortable removal |
US6191189B1 (en) | 1996-12-23 | 2001-02-20 | The Procter & Gamble Company | Adhesive for secure topical attachment to the skin and comfortable removal |
AU5531398A (en) * | 1996-12-23 | 1998-07-17 | Procter & Gamble Company, The | Disposable absorbent article with side cuffs comprising an adhesive for topica l attachment of the side cuffs to the skin of a wearer |
EP0852149A1 (en) * | 1996-12-23 | 1998-07-08 | The Procter & Gamble Company | Adhesive for secure topical attachment to the skin and comfortable removal |
EP0855190A1 (en) * | 1996-12-23 | 1998-07-29 | The Procter & Gamble Company | Adhesive for secure topical attachment to the skin and comfortable removal, particularly of absorbent articles |
CA2275990A1 (en) * | 1996-12-23 | 1998-07-02 | Fabio Cinelli | Adhesive for application of functional articles to the skin and comfortable removal of such articles |
CN1154516C (en) * | 1996-12-23 | 2004-06-23 | 普罗克特和甘保尔公司 | Adhesive for secure topical attachment to skin and comfortable removal |
EP0850619A1 (en) * | 1996-12-23 | 1998-07-01 | The Procter & Gamble Company | Disposable absorbent article for topical adhesive attachment to the skin of a wearer |
US6582711B1 (en) | 1997-01-09 | 2003-06-24 | 3M Innovative Properties Company | Hydroalcoholic compositions thickened using polymers |
US5908619A (en) * | 1997-01-09 | 1999-06-01 | Minnesota Mining And Manufacturing Company | Hydroalcoholic compositions thickened using surfactant/polymer complexes |
US6019997A (en) * | 1997-01-09 | 2000-02-01 | Minnesota Mining And Manufacturing | Hydroalcoholic compositions for transdermal penetration of pharmaceutical agents |
US6221997B1 (en) | 1997-04-28 | 2001-04-24 | Kimberly Ann Woodhouse | Biodegradable polyurethanes |
IT1292396B1 (en) * | 1997-06-23 | 1999-02-08 | Lisapharma Spa | DERMAL PATCH HAVING HIGH MECHANICAL RESISTANCE, FLEXIBILITY, TRANSPARENCY AND ELECTRICAL CONDUCTIVITY IN THE TREATMENT OF DISEASES |
US6007532A (en) | 1997-08-29 | 1999-12-28 | 3M Innovative Properties Company | Method and apparatus for detecting loss of contact of biomedical electrodes with patient skin |
US6171985B1 (en) | 1997-12-01 | 2001-01-09 | 3M Innovative Properties Company | Low trauma adhesive article |
US6093463A (en) * | 1997-12-12 | 2000-07-25 | Intella Interventional Systems, Inc. | Medical devices made from improved polymer blends |
US6099926A (en) * | 1997-12-12 | 2000-08-08 | Intella Interventional Systems, Inc. | Aliphatic polyketone compositions and medical devices |
US6331166B1 (en) * | 1998-03-03 | 2001-12-18 | Senorx, Inc. | Breast biopsy system and method |
AU3317599A (en) | 1998-06-10 | 1999-12-23 | Lintec Corporation | Blackhead removing agent, blackhead removing sheet, and method for producing blackhead removing sheet |
JP2000060815A (en) | 1998-08-17 | 2000-02-29 | Minnesota Mining & Mfg Co <3M> | Vital electrode |
US6273875B1 (en) | 1998-08-17 | 2001-08-14 | Edwards Lifesciences Corporation | Medical devices having improved antimicrobial/antithrombogenic properties |
US6338790B1 (en) * | 1998-10-08 | 2002-01-15 | Therasense, Inc. | Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator |
US6710099B2 (en) | 1999-02-02 | 2004-03-23 | The Procter & Gamble Company | Disposable absorbent articles with improved adhesive for attachment to the skin to facilitate water adhesion stability with low pain level removal |
US6607516B2 (en) | 1999-02-02 | 2003-08-19 | The Procter & Gamble Company | Disposable human waste management devices with improved adhesive flange to facilitate adhesion in oily conditions |
US6878756B2 (en) | 1999-02-02 | 2005-04-12 | The Procter & Gamble Company | Disposable human waste management devices with improved adhesive flange attachment means to facilitate water adhesion stability with low pain level removal |
US6544642B2 (en) | 1999-02-02 | 2003-04-08 | The Procter & Gamble Company | Disposable absorbent articles with improved adhesive for attachment to the skin to facilitate adhesion in oily conditions |
US6356779B1 (en) | 1999-06-04 | 2002-03-12 | 3M Innovative Properties Company | Universally functional biomedical electrode |
US6878440B1 (en) | 1999-07-02 | 2005-04-12 | 3M Innovative Properties Company | Pressure sensitive adhesive sheet and production method thereof |
US6328878B1 (en) * | 1999-08-11 | 2001-12-11 | Dacco Sci, Inc. | Adhesive tape sensor for detecting and evaluating coating and substrate degradation utilizing electrochemical processes |
US6495229B1 (en) * | 1999-09-17 | 2002-12-17 | Avery Dennison Corporation | Pattern coated adhesive article |
ATE318566T1 (en) | 2000-03-10 | 2006-03-15 | 3M Innovative Properties Co | MEDICAL WOUND DRESSING WITH MULTIPLE ADHESIVES AND MANUFACTURING METHODS |
KR100433614B1 (en) * | 2000-06-16 | 2004-05-31 | 주식회사 태평양 | Transdermal Preparation Containing Hydrophilic or Salt-form Drug |
JP4323797B2 (en) | 2000-07-07 | 2009-09-02 | エイ.ブイ.トップチーブ インスティテュート オブ ペトロケミカル シンセシス | Preparation of hydrophilic pressure sensitive adhesives with optimized adhesive properties |
USRE44145E1 (en) * | 2000-07-07 | 2013-04-09 | A.V. Topchiev Institute Of Petrochemical Synthesis | Preparation of hydrophilic pressure sensitive adhesives having optimized adhesive properties |
FR2811878B1 (en) * | 2000-07-19 | 2003-02-07 | C2C | DEVICE FOR ACQUIRING ELECTRIC SIGNALS FROM THE HUMAN BODY AND MORE PARTICULARLY FOR THE ACQUISITION OF ELECTRIC SIGNALS FROM THE HEART |
US6492573B1 (en) | 2000-08-17 | 2002-12-10 | Arthur Ashman | Biocompatible oral bandage, application and method of manufacture |
KR100372560B1 (en) * | 2000-11-02 | 2003-02-19 | 한국전력공사 | Charcoal filled hydrogels dressings and process for preparing thereof by irradiation |
US8206738B2 (en) | 2001-05-01 | 2012-06-26 | Corium International, Inc. | Hydrogel compositions with an erodible backing member |
US8840918B2 (en) | 2001-05-01 | 2014-09-23 | A. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences | Hydrogel compositions for tooth whitening |
ES2331302T3 (en) | 2001-05-01 | 2009-12-29 | A.V. Topchiev Institute Of Petrochemical Synthesis | HYDROGEL COMPOSITIONS. |
US8541021B2 (en) * | 2001-05-01 | 2013-09-24 | A.V. Topchiev Institute Of Petrochemical Synthesis | Hydrogel compositions demonstrating phase separation on contact with aqueous media |
US20050215727A1 (en) | 2001-05-01 | 2005-09-29 | Corium | Water-absorbent adhesive compositions and associated methods of manufacture and use |
US20050113510A1 (en) | 2001-05-01 | 2005-05-26 | Feldstein Mikhail M. | Method of preparing polymeric adhesive compositions utilizing the mechanism of interaction between the polymer components |
DE60239528D1 (en) * | 2001-05-01 | 2011-05-05 | Corium International Redwood City | TWO-PHASE, WATER-ABSORBING BIOADHESIVE COMPOSITION |
US20020187181A1 (en) * | 2001-05-14 | 2002-12-12 | 3M Innovative Properties Company | System for delivering cosmetics and pharmaceuticals |
ES2333037T3 (en) * | 2001-06-01 | 2010-02-16 | Covidien Ag | CABLE CONNECTOR OF A RETURN PAD. |
US6796828B2 (en) * | 2001-06-01 | 2004-09-28 | Sherwood Services Ag | Return pad cable connector |
US7027877B2 (en) | 2001-08-23 | 2006-04-11 | Zoll Medical Corporation | Method of applying defibrilator electrode pad with folded release sheet |
AU2003254674A1 (en) * | 2002-08-09 | 2004-02-25 | National Research Council Of Canada | Bio-synthetic matrix and uses thereof |
US6860881B2 (en) | 2002-09-25 | 2005-03-01 | Sherwood Services Ag | Multiple RF return pad contact detection system |
US9114156B2 (en) * | 2002-12-30 | 2015-08-25 | Aplicare, Inc. | Enhanced antimicrobial skin preparation |
US7660842B2 (en) * | 2003-05-12 | 2010-02-09 | Sun Microsystems, Inc. | Method and apparatus for performing a carry-save division operation |
US20040247654A1 (en) * | 2003-06-05 | 2004-12-09 | 3M Innovative Properties Company | Hydrophilic adhesives for delivery of herbal medicines |
US9278155B2 (en) * | 2003-06-05 | 2016-03-08 | 3M Innovative Properties Company | Adhesive compositions, articles incorporating same and methods of manufacture |
US7187985B2 (en) * | 2003-07-18 | 2007-03-06 | 3M Innovative Properties Company | Biomedical electrode with current spreading layer |
AU2003284929B2 (en) * | 2003-10-23 | 2010-07-22 | Covidien Ag | Redundant temperature monitoring in electrosurgical systems for safety mitigation |
CA2554649C (en) | 2004-01-30 | 2015-10-27 | Corium International, Inc. | Rapidly dissolving film for delivery of an active agent |
CA2576158C (en) * | 2004-08-05 | 2020-10-27 | Corium International, Inc. | Adhesive composition |
US20060073328A1 (en) * | 2004-09-21 | 2006-04-06 | Andover Coated Products, Inc. | Strapping system with non-elastic cohesive tape |
US7344672B2 (en) * | 2004-10-07 | 2008-03-18 | Biomet Manufacturing Corp. | Solid state deformation processing of crosslinked high molecular weight polymeric materials |
US8262976B2 (en) | 2004-10-07 | 2012-09-11 | Biomet Manufacturing Corp. | Solid state deformation processing of crosslinked high molecular weight polymeric materials |
US7462318B2 (en) * | 2004-10-07 | 2008-12-09 | Biomet Manufacturing Corp. | Crosslinked polymeric material with enhanced strength and process for manufacturing |
US7547405B2 (en) | 2004-10-07 | 2009-06-16 | Biomet Manufacturing Corp. | Solid state deformation processing of crosslinked high molecular weight polymeric materials |
US20060079872A1 (en) * | 2004-10-08 | 2006-04-13 | Eggleston Jeffrey L | Devices for detecting heating under a patient return electrode |
US7235592B2 (en) * | 2004-10-12 | 2007-06-26 | Zimmer Gmbh | PVA hydrogel |
US8017139B2 (en) * | 2005-02-23 | 2011-09-13 | Zimmer Technology, Inc. | Blend hydrogels and methods of making |
CA2541037A1 (en) * | 2005-03-31 | 2006-09-30 | Sherwood Services Ag | Temperature regulating patient return electrode and return electrode monitoring system |
US20060258788A1 (en) * | 2005-05-13 | 2006-11-16 | Scott Coggins | Polymeric hydrogel compositions |
US7538379B1 (en) * | 2005-06-15 | 2009-05-26 | Actel Corporation | Non-volatile two-transistor programmable logic cell and array layout |
US7620439B2 (en) * | 2005-08-04 | 2009-11-17 | 3M Innovative Properties Company | Conductive adhesives and biomedical articles including same |
US20070049914A1 (en) * | 2005-09-01 | 2007-03-01 | Sherwood Services Ag | Return electrode pad with conductive element grid and method |
US20070098799A1 (en) * | 2005-10-28 | 2007-05-03 | Zimmer, Inc. | Mineralized Hydrogels and Methods of Making and Using Hydrogels |
AU2006321809A1 (en) * | 2005-12-07 | 2007-06-14 | Zimmer, Inc. | Methods of bonding or modifying hydrogels using irradiation |
JP2007177244A (en) * | 2005-12-22 | 2007-07-12 | Zimmer Inc | Perfluorocyclobutane crosslinked hydrogel |
US7736359B2 (en) * | 2006-01-12 | 2010-06-15 | Covidien Ag | RF return pad current detection system |
US20070167942A1 (en) * | 2006-01-18 | 2007-07-19 | Sherwood Services Ag | RF return pad current distribution system |
US8110242B2 (en) * | 2006-03-24 | 2012-02-07 | Zimmer, Inc. | Methods of preparing hydrogel coatings |
US20070244478A1 (en) * | 2006-04-18 | 2007-10-18 | Sherwood Services Ag | System and method for reducing patient return electrode current concentrations |
US20080009846A1 (en) * | 2006-07-06 | 2008-01-10 | Sherwood Services Ag | Electrosurgical return electrode with an involuted edge |
US7799352B2 (en) | 2006-08-09 | 2010-09-21 | Korea Atomic Energy Research Institute | Therapeutic hydrogel for atopic dermatitis and preparation method thereof |
US7637907B2 (en) * | 2006-09-19 | 2009-12-29 | Covidien Ag | System and method for return electrode monitoring |
US7927329B2 (en) * | 2006-09-28 | 2011-04-19 | Covidien Ag | Temperature sensing return electrode pad |
US7722603B2 (en) * | 2006-09-28 | 2010-05-25 | Covidien Ag | Smart return electrode pad |
US8777940B2 (en) | 2007-04-03 | 2014-07-15 | Covidien Lp | System and method for providing even heat distribution and cooling return pads |
US8021360B2 (en) * | 2007-04-03 | 2011-09-20 | Tyco Healthcare Group Lp | System and method for providing even heat distribution and cooling return pads |
US8080007B2 (en) * | 2007-05-07 | 2011-12-20 | Tyco Healthcare Group Lp | Capacitive electrosurgical return pad with contact quality monitoring |
US8388612B2 (en) * | 2007-05-11 | 2013-03-05 | Covidien Lp | Temperature monitoring return electrode |
US8231614B2 (en) | 2007-05-11 | 2012-07-31 | Tyco Healthcare Group Lp | Temperature monitoring return electrode |
US8641959B2 (en) | 2007-07-27 | 2014-02-04 | Biomet Manufacturing, Llc | Antioxidant doping of crosslinked polymers to form non-eluting bearing components |
US8100898B2 (en) | 2007-08-01 | 2012-01-24 | Tyco Healthcare Group Lp | System and method for return electrode monitoring |
US8801703B2 (en) | 2007-08-01 | 2014-08-12 | Covidien Lp | System and method for return electrode monitoring |
US7731988B2 (en) * | 2007-08-03 | 2010-06-08 | Zimmer, Inc. | Multi-polymer hydrogels |
US8062739B2 (en) * | 2007-08-31 | 2011-11-22 | Zimmer, Inc. | Hydrogels with gradient |
MX2010004789A (en) * | 2007-11-02 | 2010-07-05 | Acrux Dds Pty Ltd | Transdermal delivery system for hormones and steroids. |
US7947784B2 (en) | 2007-11-16 | 2011-05-24 | Zimmer, Inc. | Reactive compounding of hydrogels |
GB0722974D0 (en) * | 2007-11-23 | 2008-01-02 | Leftly Steven A | Skin sensor device |
US8034362B2 (en) * | 2008-01-04 | 2011-10-11 | Zimmer, Inc. | Chemical composition of hydrogels for use as articulating surfaces |
US9242022B2 (en) * | 2008-01-18 | 2016-01-26 | 3M Innovative Properties Company | Hydrogels with tapered edge |
US8187263B2 (en) | 2008-02-04 | 2012-05-29 | Tyco Healthcare Group Lp | System and method for return electrode monitoring |
US9457123B2 (en) * | 2008-09-24 | 2016-10-04 | 3M Innovative Properties Company | Hydrogels with release element |
AU2010204986B2 (en) | 2009-01-14 | 2016-06-02 | Corium International, Inc. | Transdermal administration of tamsulosin |
JP5600737B2 (en) | 2009-04-28 | 2014-10-01 | スリーエム イノベイティブ プロパティズ カンパニー | Water-soluble pressure sensitive adhesive |
GB0912009D0 (en) * | 2009-07-10 | 2009-08-19 | Univ Strathclyde | Sensor |
US8221994B2 (en) | 2009-09-30 | 2012-07-17 | Cilag Gmbh International | Adhesive composition for use in an immunosensor |
US20120288537A1 (en) | 2010-01-13 | 2012-11-15 | The Regents Of The University Of Michigan | Active self-healing biomaterial system |
DE102010004950A1 (en) * | 2010-01-18 | 2011-07-21 | Remis Gesellschaft für Entwicklung und Vertrieb von technischen Elementen mbH, 50829 | Cooling shelf with door device |
US9346981B2 (en) | 2011-01-21 | 2016-05-24 | Avery Dennison Corporation | Chlorhexidine gluconate containing solvent adhesive |
US11058793B2 (en) | 2011-05-16 | 2021-07-13 | Avery Dennison Corporation | Adhesive containing microparticles |
BR112015019044B1 (en) | 2013-02-07 | 2022-02-08 | Avery Dennison Corporation | ANTIMICROBIAL ADHESIVE COMPOSITION, ITS MEDICAL ARTICLE, AND METHOD OF INCREASING THE RELEASE OF AN ANTIMICROBIAL AGENT FROM AN ADHESIVE COMPOSITION |
CN105209084B (en) | 2013-03-13 | 2018-07-03 | 艾利丹尼森公司 | Improved bond properties |
US11213432B2 (en) | 2013-03-15 | 2022-01-04 | Avery Dennison Corporation | Transparent cover dressing application system and inclusion of label strip |
US9586370B2 (en) | 2013-08-15 | 2017-03-07 | Biomet Manufacturing, Llc | Method for making ultra high molecular weight polyethylene |
EP3789014A1 (en) | 2014-06-05 | 2021-03-10 | Avery Dennison Corporation | Articles with active agent concentrated at the substrate contacting surface and related methods |
ES2921990T3 (en) | 2014-09-10 | 2022-09-05 | Bard Inc C R | Protective dressing for a medical device placed on the skin |
WO2016109418A1 (en) | 2014-12-30 | 2016-07-07 | 3M Innovative Properties Company | Wound dressing with multiple adhesive layers |
KR102007064B1 (en) | 2015-12-02 | 2019-08-02 | 단국대학교 산학협력단 | A wound hydrogel dressing substance with discoloring function |
US10940233B2 (en) | 2016-10-05 | 2021-03-09 | 3M Innovative Properties Company | Fibrinogen composition, method and wound articles |
US11827754B2 (en) | 2016-10-05 | 2023-11-28 | 3M Innovative Properties Company | Fibrin composition comprising carrier material, method and wound articles |
KR20190098881A (en) | 2018-02-14 | 2019-08-23 | 조석형 | Manufacturing method of polyurethane foam/ hydrofiber complex and wound dressing using polyurethane foam/ hydrofiber complex |
WO2020035811A1 (en) | 2018-08-17 | 2020-02-20 | 3M Innovative Properties Company | Wound dressing system |
Family Cites Families (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NO134790C (en) * | 1968-07-09 | 1984-03-22 | Smith & Nephew | Kleber ,; PRESSURE SENSITIVE, WATERPUME-PERMEABLE PRODUCT FOR SKIN USE BY HUMANS. |
US3900378A (en) * | 1971-11-01 | 1975-08-19 | Union Carbide Corp | Hydrogels from radiation crosslinked blends of hydrophilic polymers and fillers |
GB1439132A (en) * | 1972-03-13 | 1976-06-09 | Special Polymers Ltd | Method for the production of a hydrophilic polymer product |
US4089832A (en) * | 1973-09-18 | 1978-05-16 | Director-General Of The Agency Of Industrial Science & Technology | Water-containing plastic composition |
US4058491A (en) * | 1975-02-11 | 1977-11-15 | Plastomedical Sciences, Inc. | Cationic hydrogels based on heterocyclic N-vinyl monomers |
US4352359A (en) * | 1977-08-19 | 1982-10-05 | Minnesota Mining And Manufacturing Company | Biomedical electrode |
US4273135A (en) * | 1977-08-19 | 1981-06-16 | Minnesota Mining And Manufacturing Company | Biomedical electrode |
US4310509A (en) * | 1979-07-31 | 1982-01-12 | Minnesota Mining And Manufacturing Company | Pressure-sensitive adhesive having a broad spectrum antimicrobial therein |
AU543967B2 (en) * | 1980-01-23 | 1985-05-09 | Minnesota Mining And Manufacturing Company | Conductive adhesive and biomedical electrode |
US4524087A (en) * | 1980-01-23 | 1985-06-18 | Minnesota Mining And Manufacturing Company | Conductive adhesive and biomedical electrode |
US4539996A (en) * | 1980-01-23 | 1985-09-10 | Minnesota Mining And Manufacturing Company | Conductive adhesive and biomedical electrode |
US4750482A (en) * | 1982-02-25 | 1988-06-14 | Pfizer Inc. | Hydrophilic, elastomeric, pressure-sensitive adhesive |
CA1218954A (en) * | 1982-02-25 | 1987-03-10 | David L. Sieverding | Hydrophilic, elastomeric, pressure-sensitive adhesive |
US4699146A (en) * | 1982-02-25 | 1987-10-13 | Valleylab, Inc. | Hydrophilic, elastomeric, pressure-sensitive adhesive |
ATE17191T1 (en) * | 1982-04-08 | 1986-01-15 | Smith & Nephew Ass | SURGICAL STAPS. |
GR79380B (en) * | 1982-09-28 | 1984-10-22 | Johnson & Johnson Prod Inc | |
US4798642A (en) * | 1983-11-14 | 1989-01-17 | Minnesota Mining And Manufacturing Company | Method of making a biomedical electrode |
US4904247A (en) * | 1984-08-31 | 1990-02-27 | Kendall Company | Pressure-sensitive hydrophilic laminate structures for use in wound dressing, transdermal and topical drug delivery |
US4593053A (en) * | 1984-12-07 | 1986-06-03 | Medtronic, Inc. | Hydrophilic pressure sensitive biomedical adhesive composition |
US4795516A (en) * | 1986-05-21 | 1989-01-03 | Minnesota Mining And Manufacturing Company | Method of continuous production of a biomedical electrode |
US4646730A (en) * | 1986-05-23 | 1987-03-03 | Johnson & Johnson Products, Inc. | Color stabilized hydrogel dressing and process |
US4777954A (en) * | 1986-06-30 | 1988-10-18 | Nepera Inc. | Conductive adhesive medical electrode assemblies |
US4715382A (en) * | 1986-08-01 | 1987-12-29 | Minnesota Mining And Manufacturing Company | Flat biomedical electrode with reuseable lead wire |
US4771783A (en) * | 1986-08-01 | 1988-09-20 | Minnesota Mining And Manufacturing Company | Flat, conformable, biomedical electrode |
US4848353A (en) * | 1986-09-05 | 1989-07-18 | Minnesota Mining And Manufacturing Company | Electrically-conductive, pressure-sensitive adhesive and biomedical electrodes |
US4792400A (en) * | 1987-03-09 | 1988-12-20 | Gaf Corporation | Insoluble vinyl lactam clarifiers |
US4849224A (en) * | 1987-11-12 | 1989-07-18 | Theratech Inc. | Device for administering an active agent to the skin or mucosa |
US4931282A (en) * | 1987-11-25 | 1990-06-05 | Minnesota Mining And Manufacturing Company | Pressure-sensitive medical sealant |
US4846185A (en) * | 1987-11-25 | 1989-07-11 | Minnesota Mining And Manufacturing Company | Bioelectrode having a galvanically active interfacing material |
CA1333114C (en) * | 1987-11-25 | 1994-11-15 | Daniel C. Duan | Pressure-sensitive adhesives and bioelectrodes constructed with the adhesive |
US5225473A (en) * | 1987-11-25 | 1993-07-06 | Minnesota Mining And Manufacturing Company | Pressure-sensitive adhesives |
JP2931002B2 (en) * | 1988-02-26 | 1999-08-09 | ライカー ラボラトリース インコーポレーテッド | Skin permeation estradiol delivery system |
US4855294A (en) * | 1988-09-06 | 1989-08-08 | Theratech, Inc. | Method for reducing skin irritation associated with drug/penetration enhancer compositions |
US5012810A (en) * | 1988-09-22 | 1991-05-07 | Minnesota Mining And Manufacturing Company | Biomedical electrode construction |
US4989607A (en) * | 1989-03-30 | 1991-02-05 | Preston Keusch | Highly conductive non-stringy adhesive hydrophilic gels and medical electrode assemblies manufactured therefrom |
US5143071A (en) * | 1989-03-30 | 1992-09-01 | Nepera, Inc. | Non-stringy adhesive hydrophilic gels |
US5276079A (en) * | 1991-11-15 | 1994-01-04 | Minnesota Mining And Manufacturing Company | Pressure-sensitive poly(n-vinyl lactam) adhesive composition and method for producing and using same |
-
1991
- 1991-11-15 US US07/792,442 patent/US5276079A/en not_active Expired - Lifetime
-
1992
- 1992-10-30 WO PCT/US1992/009397 patent/WO1993010201A1/en active IP Right Grant
- 1992-10-30 DK DK92925054.6T patent/DK0612342T3/en active
- 1992-10-30 JP JP50929093A patent/JP3426231B2/en not_active Expired - Fee Related
- 1992-10-30 AT AT92925054T patent/ATE146212T1/en not_active IP Right Cessation
- 1992-10-30 CA CA002116123A patent/CA2116123A1/en not_active Abandoned
- 1992-10-30 DE DE69215893T patent/DE69215893T2/en not_active Expired - Lifetime
- 1992-10-30 EP EP92925054A patent/EP0612342B1/en not_active Expired - Lifetime
- 1992-10-30 AU AU31254/93A patent/AU657188B2/en not_active Ceased
-
1993
- 1993-10-15 US US08/139,516 patent/US5389376A/en not_active Expired - Lifetime
- 1993-10-15 US US08/137,606 patent/US5438988A/en not_active Expired - Lifetime
- 1993-10-15 US US08/137,665 patent/US5409966A/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
US5409966A (en) | 1995-04-25 |
EP0612342A1 (en) | 1994-08-31 |
DK0612342T3 (en) | 1997-06-16 |
JP3426231B2 (en) | 2003-07-14 |
ATE146212T1 (en) | 1996-12-15 |
US5389376A (en) | 1995-02-14 |
DE69215893T2 (en) | 1997-04-03 |
DE69215893D1 (en) | 1997-01-23 |
WO1993010201A1 (en) | 1993-05-27 |
EP0612342B1 (en) | 1996-12-11 |
AU3125493A (en) | 1993-06-15 |
US5438988A (en) | 1995-08-08 |
AU657188B2 (en) | 1995-03-02 |
JPH07501101A (en) | 1995-02-02 |
US5276079A (en) | 1994-01-04 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
FZDE | Discontinued |