US007829116B2

(12) United States Patent (10) Patent No.: US 7,829,116 B2 Griswold et al. (45) Date of Patent: *Nov. 9, 2010

(54) ADHESIVE-FORMING COMPOSITION AND 5,750,129 A * 5/1998 Wakarchuk ...... 424/408 BLEND OF ADHESIVES OBTANED 5,750,136 A 5/1998 Scholz et al. THEREFROM 5,767,197 A * 6/1998 Fukatsu et al...... 525,101 6,121,354 A 9, 2000 Chronister (75) Inventors: Roy M. Griswold, Ballston Spa, NY 6,133,395 A * 10/2000 Miyata et al...... 528/28 6,562,363 B1 5/2003 Mantelle et al. (US); Robert L. Frye, Concord, OH 6.746,689Iw B2 6, 2004 Fiischer et al. (US); Mark J. Bisaillon, Saratoga 6,803,412 B2 10/2004 Nguyen-Misra et al. Springs, NY (US) 6,858,997 B1 2/2005 Poindexter 6,884.852 B1 * 4/2005 Klauck et al...... 525/458 (73) Assignee: Momentive Performance Materials 6,936,661 B2 8, 2005 Koch et al. Inc., Albany, NY (US) 7,189,781 B2 * 3/2007 Acevedo et al...... 524,588 7,405,259 B2 * 7/2008 Frye et al...... 525/477 (*) Notice: Subject to any disclaimer, the term of this 2005, OO19385 A1 1/2005 Houze patent is extended or adjusted under 35 2005/0282977 A1 12/2005 Stempel et al. U.S.C. 154(b) by 679 days. 2006,0078601 A1 4/2006 Kanios et al. 2006,0078603 A1 4/2006 Nguyen This patent is Subject to a terminal dis 2006/024737O A1 1 1/2006 Frye et al. claimer. FOREIGN PATENT DOCUMENTS JP 56-082863 T 1981 (21) Appl. No.: 11/598,925 JP 57-2O7663 12/1982 JP 59-172575 9, 1984 (22) Filed: Nov. 14, 2006 JP 59-174672 10, 1984 JP 61-047774 3, 1986 (65) Prior Publication Data JP 61-218631 9, 1986 US 2008/O114098 A1 May 15, 2008 JP 61-218672 9, 1986 JP 61-218673 9, 1986 JP 62-257479 9, 1986 (51) Int. Cl. JP 62-057478 3, 1987 A 6LX 9/70 (2006.01) JP 62-05748O 3, 1987 (52) U.S. Cl...... 424/484; 424/449; 424/486; JP 62-089782 4f1987 514/1525/455; 525/458; 528/44; 528/75; JP O3-259981 11, 1991 528/85; 528/38 JP O9-165565 6, 1997 (58) Field of Classification Search ...... 524/55 WO 2004/094549 A1 11, 2004 See application file for complete search history. * cited by examiner (56) References Cited Primary Examiner Marc S. Zimmer U.S. PATENT DOCUMENTS (74) Attorney, Agent, or Firm—Dominick G. Vicari; Joseph S. Ostroff Wiggin and Dana LLP 3,627,722 A 12/1971 Seiter 3,632,557 A 1/1972 Brode et al. (57) ABSTRACT 3,979,344 A 9/1976 Bryant et al. 4,222,925 A 9/1980 Bryant et al. The present invention relates to novel adhesive-forming com 4,470,962 A 9, 1984 Keith et al. positions of silylated polyurethane prepolymer blended with 4,655,767 A * 4, 1987 Woodard et al...... 424/448 4,668,232 A 5, 1987 Cordes et al. pre-formed adhesives, and pressure sensitive adhesives con 4,837,274 A 6, 1989 Kawakubo et al. taining the same. The silylated polyurethane prepolymer is 4,900,772 A 2, 1990 Imanaka et al. obtained from the silylation of a polyurethane prepolymer 4,904,732 A 2f1990 Iwahara et al. derived from the reaction of polybutadiene polyol and poly 5,223,575 A 6, 1993 Mori et al. isocyanante, where the polybutadiene polyol possesses a pri 5,338,490 A 8, 1994 Dietz et al. mary hydroxyl group content of from about 0.1 to about 2.0 5,556,636 A 9, 1996 Yano et al. meg/g. 5,660, 178 A 8, 1997 Kantner et al. 5,725,947 A 3, 1998 Johannsen et al. 19 Claims, No Drawings US 7,829, 116 B2 1. 2 ADHESVE-FORMING COMPOSITION AND The adhesive-forming compositions of the present inven BLEND OF ADHESIVES OBTANED tion provide adhesive blends with improved peel adhesion to THEREFROM various Surfaces and other properties, e.g., improved peel adhesion for “removable' or “repositionable” labels, wound This invention relates to silylated polymers and to pressure dressings and skin attachment applications, such as, e.g., sensitive adhesive (PSA) compositions containing same. transdermal drug delivery device for modified drug delivery More specifically, this invention relates to novel adhesive rates. forming compositions comprising blends of silylated poly urethane and pre-formed adhesives. DETAILED DESCRIPTION OF THE INVENTION 10 BACKGROUND OF THE INVENTION The adhesive-forming compositions of the present inven tion contain silylated polyurethane prepolymer obtained by Adhesives are typically blended with other non-adhesive the silylation of a polyurethane prepolymer derived from the polymers or with adhesives to alter the final pressure sensitive reaction of polybutadiene polyol and polyisocyanante, and adhesive properties such as re-positionability, adhesion to 15 pre-formed adhesive. various Surfaces, and control of drug agent deliver rates. In The polyurethane prepolymer of the present invention is particular, Such blends are used in skin attachment applica derived from the reaction of polybutadiene polyol. The polyb tions including wound dressings and drug delivery. Typically utadiene polyols useful for preparing the isocyanate-termi these encompass compositions where an acrylic and silicone nated and hydroxyl-terminated polyurethane prepolymers pressure sensitive adhesives, or other organic and silicone are those possessing a number average molecular weight adhesives are blended. (Mn) of from about 500 to about 10,000, and advantageously Blended adhesive compositions are known in the art. from about 800 to about 5,000, a primary hydroxyl group U.S. Pat. No. 5,725,947 describes a film composite content of from about 0.1 to about 2.0 meq/g, and advanta wherein a first adhesive is an acrylic latex and aheat-activated geously from about 0.3 to about 1.8 med/g, a degree of hydro urethane latex, a second adhesive is applied over the first 25 genation of from 0 up to 100 percent of the olefinic sites yielding a re-positionable composite that upon extended con present and an average content of copolymerized additional tact builds adhesion. monomer(s) of from 0 up to about 50 weight percent. U.S. Pat. No. 5,338,490 describes ionically conductive Hydroxyl-terminated butadienes of the above-described hydrophilic adhesive as a continuous phase and a hydropho type, averaging more than one predominantly primary bic adhesive discontinuous phase for biomedical applica 30 hydroxyl group per molecule, e.g., averaging from about 1.7 tions. to about 3 or more primary hydroxyl groups per molecule, are Published U.S. Patent Application No. 20005/0282977 suitably employed herein. The hydroxyl-terminated polyb describes silicone pressure sensitive adhesive and silicone gel utadienes will possess an average of at least about 2, and blend for skin-attachable use. advantageously from about 2.4 up to about 2.8, hydroxyl WO 2004094549 describes compositions wherein two 35 groups per molecule, the hydroxyl groups being predomi adhesives, one with acidic functionality then other basic func nantly interminal allylic positions on the main, i.e., generally tionality, are blended then crosslinked. longest, hydrocarbon chain of the molecule. By “allylic' Several transdermal patents exist wherein the active agent configuration is meant that the alpha-allylic grouping of is incorporated into compositions of polymeric and/or pres allylic alcohol, i.e., the terminal hydroxyl groups of the poly sure sensitive adhesives. Illustrative of these are the follow 40 mer, are bonded to carbon atoms adjacent to double bonded 1ng: carbon atoms. Published U.S. Patent Application No. 20060078603 The ratio of cis-1,4, trans-1.4 and 1.2-vinyl unsaturation describes blends of acrylic adhesives with acrylic or rubber which occurs in the butadiene polymers employed in this based adhesives to provide desired drug flux in transdermal invention, the number and location of the hydroxyl groups systems. 45 and the molecular weight of the butadiene polymers will be Published U.S. Patent Application No. 200500 19385 influenced by the process employed for their manufacture, the describes blending low and high silanol concentration sili details of which are known in the art. cone pressure sensitive adhesives. Hydroxyl-terminated polybutadienes having unsaturation Published U.S. Patent Application No. 20060078601 and those hydrogenated to yield Saturated hydroxyl-termi describes acrylic-based adhesives with a second polymer 50 nated polybutadienes possessing these characteristics are selected from silicone, rubber, polyurethane, polyisobuty commercially available from several Sources and are there lene, polyvinyl ethers, styrene block copolymers, polyether fore conveniently employed herein. block copolymers, ethylene/vinyl acetate, vinyl acetate adhe The useful hydroxyl-terminated polybutadienes herein can sives, polyvinylpyrrolidones and bio-adhesives. also incorporate one or more other copolymerizable mono 55 mers which can confer particularly desirable properties upon SUMMARY OF THE INVENTION the silylated polymers herein and the pressure sensitive adhe sive compositions prepared therewith. The total amount of In accordance with the present invention, there is provided copolymerized monomer will not exceed, on average, 50 an adhesive-forming composition comprising: weight percent of the hydroxyl-terminated polybutadiene a) adhesive-forming, moisture-curable silylated polyure 60 copolymer. Included among the copolymerizable monomers thane prepolymer, the silylated polyurethane prepoly are monoolefins and dienes Such as ethylene, propylene, mer being obtained from the silylation of a polyurethane 1-butene, isoprene, chloroprene, 2.3-methyl-1,3-butadiene, prepolymer derived from the reaction of polybutadiene 1,4-pentadiene, etc., and, ethylenically unsaturated mono polyol and polyisocyanante; and, merS Such as acrylonitrile, methacrylonitrile, methylstyrene, b) pre-formed adhesive and/or adhesive-forming compo 65 methyl acrylate, methyl methacrylate, vinyl acetate, etc. nent other than the adhesive-forming, moisture-curable Alternatively or in addition thereto, the hydroxyl-terminated silylated polyurethane prepolymer (a). polybutadienes can be reacted with one or more other mono US 7,829, 116 B2 3 mers to provide hydroxyl-terminated block copolymers. Such monomers include 12-epoxides Such as ethylene oxide and propylene oxide which will provide polyether segments, R. e-caprolactone which will provide polyester segments, and the like. 5 R-NH-R2-Si-OR). The polybutadiene-based polyurethane prepolymer is obtained by reacting one or more hydroxyl-terminated, wherein R' is hydrogen or an alkyl group of from 1 to 10 optionally hydrogenated, linear or branched polybutadiene carbon atoms, R is a divalent alkylene group of from 3 to 10 homopolymers or copolymers with an organic polyisocyan carbonatoms, RandR each independently is an alkyl group ate, e.g., an organic diisocyanate, optionally together with 10 of from 1 to 6 carbon atoms or an aryl group of from 6 to 8 one or more other difunctional compounds and/or hydroxyl carbon atoms, and X has a value of 0, 1 or 2. terminated polymers, to provide (1) an isocyanate-terminated Examples of aminosilanes for use in the silylation proce polyurethane prepolymer when the total equivalents of iso dure herein are 3-aminopropyltrimethoxysilane, 3-aminopro pyltriethoxysilane, 4-amino-3,3-dimethylbutyltrimethoxysi cyanate functionality exceeds the total equivalents of 15 hydroxyl functionality, and (2) a hydroxyl-terminated poly lane, 4-amino-3,3-dimethylbutyldimethoxymethylsilane, N-methyl-3-amino-2-methylpropyltrimethoxysilane, N urethane prepolymer when the total equivalents of hydroxyl ethyl-3-amino-2-methylpropyltrimethoxysilane, N-ethyl-3- functionality exceeds the total equivalents of isocyanate func amino-2-methylpropyldiethoxymethylsilane, N-ethyl-3- tionality. amino-2-methylpropyltriethoxy silane, N-ethyl-3-amino-2- Methods of preparing polyurethane prepolymers, and sily methylpropylmethyldimethoxysilane, N-butyl-3-amino-2- lated polyurethane prepolymers are well known in the art. methylpropyltrimethoxysilane, 3 (N-methyl-2-amino-1-me See, e.g., U.S. Pat. Nos. 3,627,722,3,632,557, 3,979,344, and thyl-1-ethoxy)-propyltrimethoxysilane, N-ethyl-4-amino-3, 4.222,925, which are incorporated herein by reference. 3-dimethylbutyldimethoxymethylsilane and N-ethyl-4-ami no-3,3-dimethylbutyltrimethoxysilane trimethoxysilane, and The prepolymer is made by reacting a hydroxy-terminated 25 polymeric material with an isocyanate to provide a prepoly the like. merchain having NCO and/or OH groups at the ends thereof. For applications such as use in Sealant and coating compo The resulting polyurethane prepolymer is then reacted with a sitions, the polyurethane prepolymers can be substantially fully silylated, i.e., all, or Substantially all, of the isocyanate Sufficient amount of a silane end-capper to provide silylated groups can be reacted with silane to provide a completely polyurethane prepolymer. 30 silylated polyurethane polymer. The isocyanates that are reacted with the polyurethane However, where the silylated polyurethane polymer is to prepolymers of the present invention are organic isocyanates be incorporated into pressure sensitive adhesive composi and include any of the known and conventional organic poly tions, it is important that the silylation be conducted to less isocyanates, especially organic diisocyanates, from which than completion in order that the extent of crosslinking that polyurethane polymers have heretofore been prepared. Use 35 occurs on Subsequent cure of the silylated polymer not be so ful diisocyanates include, for example, 2,4-toluene diisocy great as to adversely affect, and even eliminate, the pressure anate, 2,6-toluene diisocyanate, 4,4' diphenyl-methanediiso sensitive adhesive characteristics of the crosslinked polymer. cyanate, isophorone diisocyanate, dicyclohexylmethane-4, In conducting a partial silylation reaction, it can be useful 4'-diisocyanate, various liquid diphenylmethane to include a primary monoamine Such as N-ethylbutylamine diisocyantes containing a mixture of 2,4- and 4.4 isomers, 40 or similar capping reactant together with the silane as the DESMODURNR (Bayer) and the like, and mixtures thereof. amine will readily end-cap isocyanate groups thereby pre Isophorone diisocyanate is especially advantageous for use in cluding them from reacting with the silane. The optimal preparing the polyurethane prepolymers herein. amounts of silane and optional amine for achieving this less than-complete silylation operation can be readily determined The polyurethane prepolymer may be prepared by mixing 45 for a given isocyanate-terminated prepolymer employing the hydroxy-terminated polymer and organic isocyanate known and conventional experimental techniques. Sillylation together at ambient temperature and pressure, although the of not more than about 95 percent, and advantageously not speed of the reaction is significantly increased if the tempera more than about 90 percent, of the total isocyanate groups ture of the reaction mixture is raised to a higher temperature, present in the prepolymer is generally Suitable for most pres for example, a temperature between 60-100° C. A molar ratio 50 Sure sensitive adhesive applications. of NCO to OH from about 1.1 to about 4.0, depending on the Sillylation of the hydroxyl-terminated polyurethane pre selection of the particular hydroxyl-terminated polybutadi polymer described herein can be accomplished by reacting ene polyol, is used to provide isocyanate-terminated polyure the prepolymer with an isocyanatosilane. Suitable isocyana thane prepolymers. A molar ratio of NCO to OH from about tosilanes are those of the general formula: 0.3 to about 0.95, and more preferably from about 0.5 to about 55 0.90, depending on the specific hydroxyl-terminated polyb utadiene polyol, is used to provide hydroxyl group-termi R2 nated polyurethane prepolymers. OCN-R-Si--OR). Sillylation of the isocyanate-terminated polyurethane pre 60 polymer described herein can be accomplished by reacting the prepolymer with a silane possessing at least one hydro wherein R' is a divalent alkylene group of from 3 to 10 carbon ly Zable group and at least one functionality which is reactive atoms, RandR each independently is an alkyl group of from for isocyanate, i.e., an active hydrogen-containing group Such 1 to 6 carbon atoms or an aryl group of from 6 to 8 carbon as hydroxyl, carboxylic acid, mercapto, primary amino or 65 atoms, and X has a value of 0, 1 or 2. secondary amino. Advantageously, the silane is a primary or Examples of Such isocyanatosilanes for use in the silyla secondary aminosilane of the general formula: tion procedure are w-isocyanatopropyltrimethoxysilane, US 7,829, 116 B2 5 6 W-isocyanatopropyltriethoxy-silane,w-isocyanatomethylpro pre-formed adhesives may be compounded with tackifiers pyltrimethoxysilane, w-isocyanatomethylpropyltriethoxy and stabilizers as is well known in the art. silane, w-isocyanatopropylmethyldimethoxysilane, w-isocy Other additional pre-formed adhesives usable in accor anatopropyldimethylmethoxysilane and W-isocyanatometh dance with the invention include, e.g., silicone elastomers ylpropyldimethylmethoxysilane, and the like. based on monomers of silanes, halosilanes, or C-C alkox As in the case of the silylated isocyanate-terminated poly ysilanes, especially polydimethylsiloxanes which may be urethanes described above, the silylation of the hydroxyl used alone or formulated with a silicone tackifier or silicone terminated polyurethane prepolymers herein will be substan plasticizer which are selected from medically acceptable sili tially complete, i.e., essentially no hydroxyl groups will be cone fluids, i.e. non-elastomeric silicones based on silanes, present following silylation, where the silylated polymers are 10 halosilanes or C-C alkoxysilanes. Typical silicone adhe to be incorporated in Such products as sealants and coatings. sives are available from GE Advance Materials—Silicones, However, silylation will be incomplete, or partial, where the e.g., SILGRIPR). silylated polymers are to be incorporated in pressure sensitive The pressure sensitive adhesive compositions made from adhesive compositions. In the case of incomplete silylation, the adhesive-forming, moisture-curable composition of the levels of silylation of not more than about 95 percent, and 15 present invention can contain one or more chain extenders advantageously, not more than about 90 percent, of the total and/or one or more other polyols. Examples of Suitable chain hydroxyl groups present in the prepolymer is generally Suit extenders are polyhydric alcohols such as ethylene glycol, able and can be achieved by appropriate adjustment of the propylene glycol, propane-1,3-diol, butane-1,4-diol, hexane amounts of isocyanatosilane being reacted for a given pre 1,6-diol, diethylene glycol, triethylene glycol, tetraethylene polymer. glycol, dipropylene glycol, triethylene glycol, tetrathylene In order to facilitate control over the extent of incomplete glycol, dipropylene glycol, tripropylene glycol, tetrapropy silylation, it may be advantageous to include a hydroxyl lene glycol and the like. Additional polyols include polyether reactive monofunctional reactant with the isocyanatosilane. polyols, polyester polyols, polyetherester polyols, polyester Suitable reactants for this purpose include monoisocyanates ether polyols, polybutadienediols, polyoxyalkylene diols, Such as n-butylisocyanate. These and similar reactants serve 25 polyoxyalkylene triols, polytetramethylene glycols, polyca to cap some of the hydroxyl groups of the prepolymer pre prolactone diols and triols, and the like, all of which possess venting them from undergoing silylation. Amounts of Such at least two primary hydroxyl groups. hydroxyl-reactive monomeric reactants and isocyanatosi Suitable catalysts useful in the preparation of the polyure lanes that can be utilized for partial silylation herein can be thane prepolymers are known in the art, e.g., organoamine readily determined for a specific hydroxyl-terminated poly 30 and organotin catalysts. Suitable catalysts include dialkyltin urethane prepolymer employing routine experimental test dicarboxylates such as dibutyltin dilaurate and dibutyltin 1ng. acetate, tertiary amines, the stannous salts of carboxylic acids The pre-formed adhesives suitable for blending with the Such as Stannous octoate and Stannous acetate, and the like. adhesive-forming, moisture-curable composition of the Pressure sensitive adhesive compositions made from the present invention include the types of adhesives that will be 35 adhesive-forming, moisture-curable composition of the readily apparent to one skilled in the art. The additional pre present invention possess Superior adhesive and cohesive formed adhesive materials can be, e.g., conventional non properties and can be obtained with the partially silylated silicone adhesives, such as, commercial non-silicone adhe polyurethanes described above. In addition to the partially sives that include compositions segmented by the type of base silylated polyurethanes, a pressure sensitive adhesive com polymer; e.g., natural rubber, styrene butadiene rubber 40 position in accordance with the invention will typically (SBR), styrene isoprene styrene (SIS), acrylic, isoprene, include one or more additives such as fillers, tackifiers, silane polyurethanes, and the like. Other pre-formed adhesives con adhesion promoters, plasticizers, Solvents, thixotropic templated herein include conventional silicone adhesives, agents, U.V. stabilizers, antioxidants, cure catalysts, etc., in Such as, commercial adhesives grouped into methyl, low phe the usual amounts. nyl, high phenyl silicones and the like. 45 Typical fillers suitable for addition to the pressure-sensitive In one embodiment of the invention, the pre-formed adhe adhesive compositions of this invention include fumed silica, sives used for blending with the adhesive-forming, moisture precipitated silica and calcium carbonates. Treated calcium curable composition of the invention include, polyurethanes; carbonates having particle sizes from about 0.07 um to about acrylic or methacrylic resins such as polymers of esters of 4 um are particularly useful and are available under several acrylic or methacrylic acid with alcohols such as n-butanol, 50 trade names: ULTRA PFLEXOR, SUPER PFLEXOR, HI n-pentanol, isopentanol, 2-methylbutanol. 1-methylbutanol, PFLEX(R) from Specialty in Minerals; WINNOFIL(R) SPM, 1-methyl pentanol, 2-methyl pentanol, 3-methyl pentanol, SPT from Zeneca Resins; HUBERCARB(R) lat, HUBER 2-ethylbutanol, isooctanol, n-decanol, or n-dodecanol, alone CARB.R. 3 Qt and HUBERCARB(R W from Huber and or copolymerized with ethylenically unsaturated monomers KOTOMITE(R) from ECC. These fillers can be used either Such as acrylic acid, methacrylic acid, acrylamide, methacry 55 alone or in combination. The fillers can comprise up to about lamide, N-alkoxymethyl acrylamides, N-alkoxymethyl 200 parts per 100 parts of the silylated polymer component(s) methacrylamides, N-tertbutylacrylamide, itaconic acid, viny with from about 80 to about 150 parts filler per 100 parts lacetate, N-branched alkyl maleamic acids wherein the alkyl polymer being Suitable for many adhesive applications. group has 10 to 24 carbon atoms, glycol diacrylates, or mix The pressure sensitive adhesive composition of the present tures of these: natural or synthetic rubbers such as styreneb 60 invention can contain from about 20 to about 60 parts, and utadiene, butylether, neoprene, polyisobutylene, polybutadi advantageously from about 30 to about 50 parts, of one or ene, and polyisoprene; polyvinylacetate; unreaformaldehyde more known of conventional tackifiers per 100 parts of sily resins; phenol formaldehyde resins; resorcinol formaldehyde lated polyurethane polymer. Examples of suitable tackifiers resins, cellulose derivatives such as ethyl cellulose, methyl are MQ silicone resins (for which a curing catalyst Such as cellulose, nitrocellulose, cellulose acetatebutyrate, and car 65 benzoyl peroxide will ordinarily be included), terpene oligo boxymethyl cellulose; and natural gums such as guar, acacia, mers, coumarone/indene resins, aliphatic, petrochemical res pectins, starch, dextrin, albumin, gelatin, casein, etc. The ins, and modified phenolic resins. US 7,829, 116 B2 7 8 Silane adhesion promoters can be employed at levels of Xylene; aliphatic hydrocarbons such as hexane, heptane, and from about 0.5 to about 5 parts per hundred parts of the cyclohexane; halogenated hydrocarbon solvents such as silylated polyurethane polymer with from about 0.8 to about trichloroethane and chloroform; naphthas such as petroleum 1.5 parts per hundred parts polymer being especially advan ether, and oxygenated solvents such as hydrocarbon ethers, tageous. Suitable adhesion promoters include SILOUEST(R) e.g., tetrahydrofuran and the dimethylether of ethylene gly A-1120 silane, SILOUESTR A-2120 silane, SILOUESTR) col, ketones Such methyl, isobutyl ketone and esters such as A-1170 silane and SILOUESTRA-187 silane, all of which ethyl acetate and the like. Mixtures of organic Solvents can are available from GE Advanced Materials-Silicones. also be used. Exemplary plasticizers include phthalates, dipropylene The components of the adhesive-forming composition of and diethylene glycol dibenzoates and mixtures thereof, 10 this invention can be mixed in any manner Such as in bulk or epoxidized soybean oil, and the like. Dioctyl and diisode in organic solvent. The MQsilsesquioxane resin is a solid and cylphthalate are commercially available under the trade is conveniently prepared and handled in an organic solvent, names JAYFLEXOR DOP and JAYFLEXOR DIDP from Exxon the preparation of the composition of this invention prefer Chemical. The dibenzoates are available as BENXOFLEXOR) ably uses an organic solvent for the mixing of the MQ resin 9-88, BENZOFLEXOR) 50 and BENZOFLEXOR 400 from Vel 15 and siloxane gum. The mixing of the components can be sicol Chemical Corporation. Epoxidized soybean oil is avail accomplished by any of the techniques known in the art, Such able from Houghton Chemical Corporation as FLEXOL(R) as milling, blending, stirring, and the like, either in batch or in EPO. The plasticizer can comprise up to about 100 parts of the continuous process. silylated polyurethane polymer with from about 40 to about The adhesive-forming composition of this invention can be 80 parts per hundred parts of silylated polymer being satis prepared, with or without the aid of solvent, by simply mixing factory in many cases. the MQ resin, silicone gum, and catalyst together in the stated Useful solvents include aromatic, aliphatic and esters rang proportion. The order of mixing of the components is not ing in amounts of from about 25 to about 75 perhundred parts critical. by weight of silylated polyurethane prepolymer. The adhesive-forming composition of this invention is use Illustrative of useful thixotropic agents are various castor 25 ful as a pressure sensitive adhesive that readily adheres to a waxes, fumed silica, treated clays and polyamides. These rigid or flexible substrate. additives typically comprise about 1 to about 10 parts per According to another embodiment of the present invention, hundred parts of silylated polyurethane prepolymer with a transdermal drug delivery device is characterized by the use from about 1 to about 6 parts being useful for most applica of the adhesive-forming composition of the present invention. tions. The thixotropes include those available as: AEROSILR) 30 The drug for this embodiment of the present invention can be from Degussa, CABO-SIL(RTS 720 from Cabot, CASTOR any transdermally absorbable pharmaceutical, e.g., any of WAX(R) from CasChem, THIXATROL(R) and THIXCINR) those referred to in U.S. Pat. Nos. 6,746,689, 6,858,997, from Rheox and DISLONR) from King Industries. If the 6,562,363, 5,556,636 5,660,178 and 4,470,962 the entire thixotrope is reactive with silane (e.g., silica), adjustments to contents of which are incorporated herein by reference. the amount formulated may be needed to compensate there 35 In one embodiment of the invention, a transdermal drug for. delivery device contains a backing material on which the U.V. stabilizers and/or antioxidants can be incorporated adhesive-forming composition of the present invention can into the pressure sensitive adhesive compositions of this be applied using methods well known to those skilled in the invention in an amount of from 0 to about 5 parts per hundred art. The backing material is preferably a flexible film that parts silylated polyurethane polymer with from about 0.5 to 40 prevents bulk fluid flow and is inert to the ingredients of the about 2 parts providing generally good results. These mate adhesive-forming composition. In the case of adhesive-form rials are available from Ciba-Geigy under the trade names ing composition that contains a drug intended to be delivered TINUVINR 770, TINUVINR 327, TINUVINR 213, TINU across the skin Surface and intended to have systemic action, VINR 622 and IRGANOXOR) 1010. the backing is preferably Substantially resistant to the migra Suitable cure catalysts are the same as those previously 45 tion of the drug therethrough. The backing material can be described for preparation of the silylated polyurethane poly any of the conventional materials used as backing for tapes or mers. The catalysts typically compromise from about 0.01 to dressings, such as polyethylene, polypropylene, ethylene about 3 parts per hundred parts polymer with from about 0.01 vinyl acetate copolymer, ethylene propylene diene copoly to about 1.0 parts per hundred parts of polymer being entirely mer, polyurethane, rayon, and the like. Non-woven materials Suitable in many cases. 50 Such as polyesters, polyolefins, and polyamides can also be After mixing, the pressure sensitive adhesive compositions used. Also, a layer of a hydrophobic elastomer Such as poly are cured by exposure to moisture. Curing conditions typi isobutylene can function as a backing, as well as other known cally include ambient temperature, e.g., about 23°C. and 50% and convention materials in the art. relative humidity for 3 days and 37° C. and 95% relative Non-limiting examples of pharmaceutical compounds humidity for another 4 days. Alternatively water can be dis 55 include antibiotics Such as penicillins, cephalosporins, eryth Solved in an appropriate solvent such as isopropanol followed romycins, tetracyclines, macrollides, aminoglycosides, fosfo by mixing with the adhesive composition and coated, cured in mycins and rifampicins; antipyretics, analgesics and anti conventional adhesive cure ovens known in the art. inflammatory drugs such as mefenamic acid, flufenamic acid, The pressure sensitive adhesive compositions prepared indometacin, diclofenac, acetaminophen, alclofenac, from the adhesive-forming composition of the present inven 60 oxyphenbutaZone, phenylbutaZone, ibuprofen, ketoprofen, tion can optionally further comprise from about 20% to about salicylic acid, methyl salicylate, L-menthol, camphor, Sulin 70% by weight, preferably from about 0% to about 60% by dac, naproxen, fenbufen, aspirin, Sulpyrine, tiaramide hydro weight, and most preferably from 40% to about 50% by chloride and piroXicam, antihistaminics such as alpha-chlor weight of an organic solvent. Suitable organic solvents pheniramine maleate, diphenylpyraline, diphenhydramine, include any of the solvents conventionally used with organ 65 clemastine fumarate and promethazine hydrochloride; psy siloxanes and have a boiling point below approximately 250° chotropic drugs for hypnosis, sedation and ataraxia Such as C. Such as aromatic hydrocarbons, e.g., benzene, toluene and diazepam, chlorpromazine hydrochloride, chlordiazepoxide, US 7,829, 116 B2 10 Sulpiride, haloperidol, ethyl loflazepate, fluphenazine, thior embodiment of the invention, the drug can be present in a idazine, fludiazepam, flunitrazepam, phenobarbital, amobar drug reservoir of the transdermal drug delivery device. bital, cyclobarbital, triazolam and nitrazepam, coronary The adhesive-forming composition can contain other vasodilators such as nitroglycerin, isosorbide dinitrate, nitro ingredients, for example excipients such as dyes, penetration glycol, erythritol tetranitrate, pentaerythritol tetranitrate, enhancers, water-soluble or water-swellable fibrous reinforc Verapamyl (hydrochloride), nifedipine, dipyridamole and dil ers, and the like under circumstances and in amounts easily tiazem hydrochloride; antiarrhythmics and antihypertensive determined by those skilled in the art. drugs such as propranolol (hydrochloride), pindolol, cloni The adhesive-forming composition according to the inven dine (hydrochloride), bupranolol, indenolol, nilvadipine, tion exhibits excellent skin adhesion properties, even under nipradillol, bucumolol, hydrazinc hydrochloride, ace-inhibi 10 the most difficult conditions. Furthermore, when the duration tors, calcium channel blockers and the like; hypotensive of application has terminated, e.g., removal of the transder diuretics such as hydrothiazide, benzylhydrochlorothiazide mal drug delivery device provided with the adhesive-forming and cyclopenthiazide and diuretics such as furosemide, composition of the present invention, it can be removed from mefruside, trichlormethiazide and thiobromine; chemothera the skin without leaving any residues whatsoever. Compared peutic drugs such as aciclovir, nalidixic acid and Sulfa drugs; 15 to pressure sensitive adhesives made exclusively on the basis anticancer agents such as 5-FU, Vincristine, adriamycin, of polyacrylates or polyamine salts, a pressure sensitive adhe bleomycin, mitomycin, cisplatin and therarubicin; antiemet sive of the present invention also has better release properties ics agents such as metoclopramide, clebopride, Scopolamine for the active substances dissolved or dispersed therein. A (hydrobromide) and domperidone; vitamins such as vitamin further advantage of the pressure sensitive adhesives prepared A. vitamin E. Vitamin K, ergocalciferol, cholecalciferol, octo from the adhesive-forming composition according to the tiamine and riboflavin tetrabutyrate; antispasmodics Such as invention is that it is possible to add other pre-formed adhe nitrazepam, clonazepam, baclofen and meprobamate; anti sives, e.g., polyacrylates, and others as disclosed in U.S. Pat. tussives Such as dextromethorphane, terbutaline (sulfate), Nos. 6,936,661 and 5,750,136, the contents of which are ephedrine (hydrochloride), salbutamol (hemisulfate), isopro incorporate herein by reference, which are already well terenol and trimetoquinol hydrochloride; cardiacs Such as 25 known and commercially available in pharmaceutical tech prenylamine lactate, digitoxin and digoxin; vaso-constric nology and which are approved by the FDA. tors, e.g., epinephrine, ephedrine and the like; anesthetics The following examples are illustrative of the silylated Such as lidocaine, benzocaine and ethyl-p-aminobenzoate; polymers of this invention and solvent-resistant pressure sen cerebrovascular improvers such as hydergine, ergot alkaloid sitive adhesive compositions containing same. and ifenprodil; antifungal drugs such as pentamycin, ampho 30 tericin B. pyrrolnitrin, clotrimazole, benzalkonium chloride, Example 1 nitrofuraZone, nystatin and acetosulfamine; steroids such as hydrocortisone, prednisolone, paramethasone, beclometha Example 1 (Consists of Adhesives I and II and illustrates Sone dipropionate, flumethasone, betamethasone, betametha 35 blending silayted polyurethane adhesive with conventional Sone Valerate, dexamethasone, triamcinolone, triamcinolone non-silicone adhesives) acetonide, fluocinolone, fluocinolone acetonide, clobetasol Adhesive I consisted of 25 g of adhesive of SPUR" propionate, progesterone, testosterone and estradiol; anti 2000PSA prepared as follows: To a resin reaction vessel parkinsonism drugs such as L-dopa, bromocriptine mesilate, equipped with mixing capability, condenser, nitrogen atmo trihexyphenidyl hydrochloride, mazaticol hydrochloride and 40 sphere and heating was added 72.5g of hydroxyl terminated biperidenhydrochloride; and biologics such as TRH. LHRH, polybutadiene Krasol-LBH-P 2000 resin containing a TNF, lymphotoxin, interferon, urokinase, insulin, calcitonin, hydroxyl number of 46, 145.0 g of hydroxyl terminated their derivative polypeptides and prostaglandins. Others such polybutadiene Krasol-LBH-P 5000 resin containing a as tolbutamide and other antidiabetic drugs, colchicine and hydroxyl number of 21.7, 32.5 g of hydroxyl terminated other anti-gout drugs and nicotine and other Smoking Sup 45 polybutadiene Poly-bd R2OLM resin containing a hydroxyl pressors. number of 101 and 400.3 g of ethyl acetate. Refluxed for 2 The backing with an adhesive-forming composition hours to dry the mixture followed by cooling to 75-80°C. To applied thereto can be made into a patch with a backing by this was added 0.27 g of a 10 wt % toluene solution of die-cutting individual patches from the sheet. Transdermal dimethylbis (1-oxoneodecyl)oxylstannane with agitation for drug patches are known in the art, e.g. those referred to in U.S. 50 15 minutes. Next 18.6 g of isophorone diisocyanate was Pat. No. 4,668.232. Alternatively, a patch with no backing can added for an NCO/OH equivalent ratio of 0.95. The reactants be prepared by die-cutting individual patches from a coated were heated at 75-80° C. until the wt % NCO was determined release liner prepared by methods know in the art or by per standard methodology and found to be 0.0 wt % followed die-cutting from a sheet of bioadhesive composition prepared by drop wise addition of 1.34 g isocyanatopropyltrimethox by pressing between two sheets of release liner. A patch can 55 ysilane. Heating was continued until wt % NCO was 0.0 wt % be of any suitable size and shape, e.g., a 1 cm circular disk. then cool to room temperature.) The silylated polybutadiene In one embodiment of the invention, a drug is incorporated polyurethane was diluted to 30 weight percent Solids using into the adhesive-forming composition of the invention. The 9.8g ethyl acetate, 0.5 g water and one drop of a 10 weight drug is preferably present in an effective amount, which will percent dibutyltin bis(acetylacetonate) in toluene were thor depend upon the particular drug used, the intended therapy, 60 oughly mixed. Adhesive II consisted of a 25 g of Aeroset and the desired duration of use of a particular individual 1085-Z-38 (acrylic adhesive from Ashland Chemical) and 6.7 application of the adhesive-forming composition containing g ethyl acetate. Adhesives I and II were blended then bar the drug. Practical limitations on the amount of drug incor coated to give a 25 micron adhesive thickness on 50 micron porated in a composition are that amount above which the PET film, airdried 10 minutes then cured 30 minutes at 80°C. composition begins to lose adhesion to askin Surface, and that 65 The blends were then tested after one week at room tempera amount below which atherapeutically effective blood level of ture. Peel adhesion per PSTC-101 was performed, except a drug cannot be achieved and/or maintained. In another glass panel rather than the standard stainless steel test panel US 7,829, 116 B2 11 12 was used. As indicated in Table 1, such adhesive blends can be followed by cooling to approximately 75° C. To this was prepared without altering significantly the peel adhesion added 0.27g of a 10 wt.% toluene solution of dimethylbis(1- properties. oXoneodecyl)oxystannane with agitation for 15 minutes. Next 18.5 g of isophorone diisocyanate was added for an TABLE 1. NCO/OH equivalent ratio of 0.945. The reactants were heated at approximately 75° C. until the wt % NCO was determined Ratio of Adhesive Peel Adhesion, per standard methodology and found to be 0.005 wt % then III g25 mm cooled to room temperature. 1OOO 1311 Coatings were prepared from blend ratios presented in 75/25 1SOO 10 50/50 1028 Table 3, and bar coating 2 mil polyester film to yield an Of 100 1462 approximate 1.0 mil dry adhesive thickness. The adhesive was air-dried 10 minutes, followed by 2 minutes at 150° C. Peel adhesion per PSTC-101 using both stainless steel and glass panels were used. Table 3 below indicates such adhesive Example 2 15 blends can be prepared without altering significantly the peel adhesion properties. Example 2 (Consists of Adhesives I, II and III and illus trates blending silylated polyurethane adhesive with conven TABLE 3 tional silicone adhesives) Adhesive I of Example 1 was prepared. Adhesive II con Ratio of Peel Adhesion, Peel Adhesion, Probe Tack, Probe Tack, sisted of 25 g of a high phenyl content silicone adhesive Adhesive Stainless Steel, Glass, 100 g/cm, 1000 g/cm, SILGRIPR PSA6574 (a dimethyldiphenylsiloxane copoly III g/25 mm g25 mm g/cm g/cm mers with MQ resin tackifier, available from GE Advanced 10O.O 551 330 433 415 80.2O 1051 431 430 431 Materials-Silicones) and 10 g toluene. Adhesive III consisted 60/40 1278 856 472 505 of 25g of a low phenyl content adhesive SILGRIPRPSA950 25 40.60 1177 803 474 450 (a dimethyldiphenylsiloxane copolymers with MQ resin 20.80 1713 1441 531 S4O tackifier, available from Ashland Chemical) and 10g toluene. Adhesives I, II, and III were blended as presented in Table 2 below and then bar coated to give a 25 micron adhesive Example 4 thickness on 50 micron PET film, air dried 10 minutes then 30 cured 5 minutes at 150° C. These were then tested after one week at room temperature. Peel adhesion per PSTC-101 Example 4 (Consists of Adhesives I and II and illustrates using standard stainless steel test panels was performed. blending with silylated polyurethane adhesive and conven Blending with silicone adhesives improved probe tack an tional silicone adhesives with peroxide catalyst) indication of how well an adhesive wets out a surface without 35 Adhesive I of Example 1 was prepared. Adhesive II con altering peel adhesion. sisted of 25 g of a low phenyl content adhesive SILGRIPR) PSA950 and 0.07 g benzoyl peroxide dissolved in 10 g tolu TABLE 2 ene. Adhesives I and II were blended as presented in the Table 4 below then bar coated to give a 40 micron adhesive thick Ratio of III III 40 ness on 50 micron PET film, air dried 10 minutes then cured Adhesive Peel Adhesion, Probe Tack, Probe Tack, 5 minutes at 150° C. The blends were tested after one week at Blends g25 mm 100 g/cm 1000 g/cm2 room temperature. Peel adhesion per PSTC-101 using stan 1OOOO 1311 400 600 dard Stainless steel test panels. 50/500 1461 1231 1359 50,050 1351 1120 1149 45 TABLE 4 Ratio of III Adhesive Peel Adhesion, Example 3 Blends g/25 mm 10O.O 895 Example 3 (Consists of Adhesives I and II and illustrates 50 90.10 592 blending with a silylated polybutadiene polyurethane pres 80.2O 785 Sure sensitive adhesive and a polybutadiene polyurethane) 70.30 765 Adhesive I consisted of 25 g of adhesive of SPUR" 60/40 884 2000PSA', a silylated polybutadiene polyurethane was Of 100 999 diluted to 30 weight percent solids using 9.8g ethyl acetate, 55 0.5 g water and one drop of a 10 weight percent dibutyltin bis(acetylacetonate) in toluene thoroughly mixed. Example 5 Adhesive II a non-silylated polybutadiene polyurethane was prepared as follows: To a resin reaction vessel equipped Example 5 (Consists of Adhesives I and II and illustrates with mixing capability, condenser, nitrogen atmosphere and 60 blending with two silylated polyurethane adhesives of differ heating was added 72.5g of hydroxyl terminated polybuta ent compositions) diene Krasol-LBH-P 2000 resin containing a hydroxyl num Adhesive I of Example 1 was prepared. Adhesive II con ber of 46, 145.0 g of hydroxyl terminated polybutadiene sisted of a silylated polyester polyurethane and was prepared Krasol-LBH-P 5000 resin containing a hydroxyl number of as follows: To a resin reaction vessel equipped with mixing 21.7, 32.5g of hydroxyl terminated polybutadiene Poly-bd 65 capability, condenser, nitrogen atmosphere and heating was R20LM resin containing a hydroxyl number of 101 and 333.2 added 14.0 g of hydroxyl terminated poly(diethylene glycol g of ethyl acetate. Refluxed for 2 hours to dry the mixture glycerine adipate) resin containing a hydroxyl number of 90 US 7,829, 116 B2 13 14 with approximately 4.2 OH per molecule, 126.0g poly(1,4- 5. The adhesive-forming composition of claim 4 wherein butanediol neopentylglycol adipate) diol resin containing a the aminosilane is of the general formula: hydroxyl number of 35, and 221.4 g of ethyl acetate. Refluxed for 2 hours to dry the mixture followed by cooling to approxi mately 75° C. To this was added 0.09 g of a 10 wt % toluene R. solution of dimethylbis(1-oxoneodecyl)oxystannane with agitation for 15 minutes. Next 10.6 g of isophorone diisocy R-NH-R-Si--OR). anate was added for an NCO/OH equivalent ratio of 0.93. The reactants were heated at approximately 75° C. until the wt % wherein R' is hydrogen or an alkyl group of from about 1 to NCO was determined perstandard methodology and found to 10 be 0.00 wt % then 1.3 g isocyanatopropyltrimethoxysilane about 10 carbon atoms, R is a divalent alkylene group of was added and heated until 0.00 wt % NCO determined. from about 3 to about 10 carbon atoms, R and R' each Adhesives I and II were blended 50/50 w/w thenbar coated independently is an alkyl group of from about 1 to about 6 to give a 40 micron adhesive thickness on 50 micron PET carbon atoms or an aryl group of from about 6 to about 8 film, air dried 10 minutes then cured 2 minutes at 150° C. 15 carbonatoms, and X has a value of 0, 1 or 2 and the isocyana These were then tested after one week at room temperature. tosilane is of the general formula: Peel adhesion per PSTC-101 using standard stainless steel test panels the results of which are presented in Table 5. R2 TABLE 5 OCN-R-Si--OR). Ratio of III Adhesive Peel Adhesion, wherein R' is a divalent alkylene group of from about 3 to Blends g25 mm about 10 carbon atoms, Rand Reach independently is an 10O.O 895 25 50/50 1257 alkyl group of from about 1 to about 6 carbon atoms oran aryl Of 100 1349 group of from about 6 to about 8 carbon atoms, and X has a value of 0, 1 or 2. 6. The adhesive-forming composition of claim 5 wherein While the process of the invention has been described with the aminosilane is selected from the group consisting of reference to certain embodiments, it will be understood by 30 3-aminopropyltrimethoxysilane, 3-aminopropylthethoxysi those skilled in the art that various changes may be made and lane, 4-aminobutyltriethoxy-silane, N-methyl-3-amino-2- equivalents may be substituted for elements thereof without methylpropyltrimethoxysilane, N-ethyl-3-amino-2-methyl departing from the scope of the invention. In addition, many propyltrimethoxysilane, N-ethyl-3-amino-2-methylpropyl modifications may be made to adapt a particular situation or diethoxymethylsilane, N-ethyl-3-amino-2-methylpropyltri material to the teachings of the invention without departing 35 ethoxysilane, N-ethyl-3-amino-2-methylpropyl-methyldi from the essential scope thereof. Therefore, it is intended that methoxysilane, N-butyl-3-amino-2-methylpropyltrimethox the invention not be limited to the particular embodiment ysilane, 3-(N-methyl-2-amino-1-methyl-1-ethoxy)-propylt disclosed as the best mode contemplated for carrying out the rimethoxysilane, N-ethyl-4-amino-3,3-dimethyl-butyldi process of the invention but that the invention will include all methoxymethylsilane, N-ethyl-4-amino-3,3-dimethylbutylt embodiments falling within the scope of the appended claims. 40 rimethoxy-silane, N-(cyclohexyl)-3-aminopropyltrimethox ysilane, N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, What is claimed is: N-(2-aminoethyl)-3-aminopropyltriethoxy-silane, N-(2- 1. An adhesive-forming composition comprising: aminoethyl)-3-aminopropylmethyldimethoxysilane, amino a) adhesive-forming, moisture-curable silylated polyure propyltriethoxysilane, bis-(3-trimethoxysilyl-2-methylpro thane prepolymer, the silylated polyurethane prepoly 45 pyl)amine and N-(3'-trimethoxysilylpropyl)-3-amino-2- mer being obtained from the silylation of a polyurethane methylpropyltrimethoxysilane and mixtures thereof, and prepolymer derived from the reaction of polybutadiene wherein the isocyanatosilane is selected from the group con polyol and polyisocyanate, wherein the polybutadiene sisting of W-isocyanatopropyltrimethoxysilane, w-isocy polyol possesses a number average molecular weight of anatopropyltriethoxy-silane, w-isocyanatomethylpropyltri from about 500 to about 10,000 and possesses a primary 50 methoxysilane, W-isocyanatomethylpropyltriethoxysilane, hydroxyl group content of from about 0.1 to about 2.0 W-isocyanatopropylmethyldimethoxysilane, w-isocyanato meg/g, and, propyldimethylmethoxysilane and W-isocyanatomethylpro b) adhesive other than the adhesive-forming, moisture pyldimethylmethoxysilane, and mixtures thereof. curable silylated polyurethane prepolymer (a), wherein 7. The adhesive-forming composition of claim 1 wherein the adhesive is selected from the group consisting of 55 polyurethane adhesives, acrylic adhesives, silicone component (b) is moisture-curable silylated polyurethane adhesives, and combinations thereof. resin. 2. The adhesive-forming composition of claim 1 further 8. The adhesive-forming composition claim 1 further com comprising at least one catalyst for the polyurethane prepoly prising at least one additional component selected from the mer reaction. 60 group consisting of filler, tackifier, silane adhesion promoter, 3. The adhesive-forming composition of claim 1 wherein plasticizer, Solvent, thixotropic agent, U.V. stabilizer, antioxi the polybutadiene polyol possesses a number average dant and curing catalyst. molecular weight of from about 800 to about 5,000. 9. The adhesive-forming composition of claim 8 wherein 4. The adhesive-forming composition of claim 1 wherein the tackifier is MQ tackifier resin containing curing catalyst the polyurethane prepolymer is silylated with at least one 65 therefor. compound selected from the group consisting of aminosilane 10. An adhesive composition resulting from the moisture and isocyanatosilane. curing of the adhesive-forming composition of claim 1. US 7,829, 116 B2 15 16 11. The adhesive composition of claim 10 further compris group consisting of penicillins, cephalosporins, erythromy ing a therapeutically effective amount of drug. cins, tetracyclines, macrollides, aminoglycosides, fosfomy 12. The adhesive composition of claim 11 wherein the drug cins and rifampicins, mefenamic acid, flufenamic acid, is at least one member selected from the group consisting of indometacin, diclofenac, acetaminophen, alclofenac, penicillins, cephalosporins, erythromycins, tetracyclines, 5 oxyphenbutaZone, phenylbutaZone, ibuprofen, ketoprofen, macrollides, aminoglycosides, fosfomycins, rifampicins, salicylic acid, methyl salicylate, L-menthol, camphor, Sulin mefenamic acid, flufenamic acid, indometacin, diclofenac, dac, naproxen, fenbufen, aspirin, Sulpyrine, tiaramide hydro acetaminophen, alclofenac, oxyphenbutaZone, phenylbuta chloride, piroXicam, chlorpheniramine maleate, diphe Zone, ibuprofen, ketoprofen, Salicylic acid, methyl salicylate, nylpyraline, diphenhydramine, clemastine fumarate, L-menthol, camphor, Sulindac, naproxen, fenbufen, aspirin, 10 promethazine hydrochloride, diazepam, chlorpromazine Sulpyrine, tiaramide hydrochloride, piroXicam, chlorphe hydrochloride, chlordiazepoxide, Sulpiride, haloperidol, niramine maleate, diphenylpyraline, diphenhydramine, ethyl loflazepate, fluiphenazine, thioridazine, fludiazepam, clemastine fumarate, promethazine hydrochloride, diaz flunitrazepam, phenobarbital, amobarbital, cyclobarbital, epam, chlorpromazine hydrochloride, chlordiazepoxide, triazolam and nitrazepam, nitroglycerin, isosorbide dinitrate, Sulpiride, haloperidol, ethyl loflazepate, fluphenazine, thior 15 nitroglycol, erythritol tetranitrate, pentaerythritol tetrani idazine, fludiazepam, flunitrazepam, phenobarbital, amobar trate, Verapamyl. nifedipine, dipyridamole, diltiazem hydro bital, cyclobarbital, triazolam, nitrazepam, nitroglycerin, chloride, propranolol, pindolol, clonidine, bupranolol, inde isosorbide dinitrate, nitroglycol, erythritol tetranitrate, pen nolol, nilvadipine, nipradillol, bucumolol, hydrazine taerythritol tetranitrate, Verapamyl. nifedipine, dipyridamole, hydrochloride, rescinnamine, hydrothiazide, benzylhydro diltiazem hydrochloride, propranolol, pindolol, clonidine, chlorothiazide, cyclopenthiazide, furosemide, mefruside, bupranolol, indenolol, nilvadipine, nipradillol, bucumolol. trichlormethiazide, thiobromine, aciclovir, nalidixic acid, hydrazine hydrochloride, ace-inhibitor, calcium channel 5-FU, Vincristine, adriamycin, bleomycin, mitomycin, cispl blocker, rescinnamine, hydrothiazide, benzylhydrochlorothi atin, therarubicin, metoclopramide, clebopride, Scopolamine, azide, cyclopenthiazide, furosemide, mefruside, trichlorme domperidone, vitamin A, vitamin E. Vitamin K, ergocalcif thiazide, thiobromine, aciclovir, nalidixic acid, 5-FU, Vinc 25 erol, cholecalciferol, octotiamine, riboflavin tetrabutyrate, ristine, adriamycin, bleomycin, mitomycin, cisplatin, nitrazepam, clonazepam, baclofen, meprobamate, dex therarubicin, metoclopramide, clebopride, Scopolamine, tromethorphan, terbutaline, ephedrine, salbutamol, isoproter domperidone, Vitamin A, vitamin E. Vitamin K, ergocalcif enol, trimetoquinol hydrochloride, prenylamine lactate, digi erol, cholecalciferol, octotiamine, riboflavin tetrabutyrate, toxin, digoxin, lidocaine, benzocain, ethyl-p-aminobenzoate, nitrazepam, clonazepam, baclofen, meprobamate, dex 30 ergot alkaloid, ifenprodil, pentamycin, amphotericin B. pyr tromethorphane, terbutaline, ephedrine, Salbutamol, isoprot rolnitrin, clotrimazole, benzalkonium chloride, nitrofura erenol, trimetoquinol hydrochloride, prenylamine lactate, Zone, nystatin, acetosulfamine, hydrocortisone, predniso digitoxin, digoxin, lidocaine, benzocain, ethyl-p-aminoben lone, paramethasone, beclomethasone dipropionate, Zoate, ergot alkaloid, ifenprodil, pentamycin, amphotericin flumethasone, betamethasone, betamethasone Valerate, dex B. pyrrolnitrin, clotrimazole, benzalkonium chloride, nitro 35 amethasone, triamcinolone, triamcinolone acetonide, fluoci furaZone, nystatin, acetosulfamine, hydrocortisone, pred nolone, fluocinolone acetonide, clobetasol propionate, nisolone, paramethasone, beclomethasone dipropionate, flu progesterone, testosterone, estradiol, L-dopa, bromocriptine methasone, betamethasone, betamethasone Valerate, mesilate, trihexyphenidyl hydrochloride, mazaticol hydro dexamethasone, triamcinolone, triamcinolone acetonide, chloride, biperiden hydrochloride, TRH, LHRH TNF, lym fluocinolone, fluocinolone acetonide, clobetasol propionate, 40 photoxin, interferon, urokinase, insulin, calcitonin, their progesterone, testosterone, estradiol, L-dopa, bromocriptine derivative polypeptides, prostaglandins, tolbutamide, colchi mesilate, epinephrine, ephedrine, pseudoephedrine, trihex cines, and nicotine. yphenidyl hydrochloride, mazaticol hydrochloride, biperiden 15. The transdermal drug delivery device of claim 13 hydrochloride, TRH. LHRH, TNF, lymphotoxin, interferon, wherein the drug is present in the adhesive composition. urokinase, insulin, calcitonin, their derivative polypeptides, 45 16. The transdermal drug delivery device of claim 13 pos prostaglandins, tolbutamide, colchicines, and nicotine. sessing a drug reservoir, the drug being present in the drug 13. A transdermal drug delivery device which comprises: reservoir. a) a backing layer; 17. In a transdermal drug delivery device which includes an b) the adhesive composition of claim 10 applied to at least adhesive component for affixing the device to skin, the a portion of the Surface of the backing layer for securing 50 improvement which comprises as adhesive component the the backing layer to skin; and adhesive composition of claim 10. c) therapeutically effective amount of drug, the drug being 18. The composition of claim 1 wherein component (b) is contained in adhesive composition (b) and/or in an high phenyl or low phenyl silicone. optional drug reservoir in, or attached to, backing layer 19. The composition of claim 1 wherein component (b) is (a). 55 polyurethane adhesive. 14. The transdermal drug delivery device of claim 13 wherein the drug is at least one member selected from the k k k k k