1111111111111111111111111111)11j!!!111181!11111111111111111111111111 1111111111111111111111111111)11j!!!111181!11111111111111111111111111 1111111111111111111111111111)11j!!!111181!11111111111111111111111111
`
`US006159498A
`[11] Patent Number:
`
`
`[n] (cid:9) Patent Number: (cid:9)[n] (cid:9) Patent Number: (cid:9)[n] (cid:9) Patent Number: (cid:9)
`
`
`[45] (cid:9) Date of Patent: (cid:9)[45] (cid:9) Date of Patent: (cid:9)[45] (cid:9) Date of Patent: (cid:9)
`[45] Date 0f Patent:
`
`.
`
`
`
`United States Patent [19] United States Patent [19] United States Patent [19]
`Ulllted States Patent [19]
`
`
`Tapolsky et al. Tapolsky et al. Tapolsky et al.
`Tap0lsky et al.
`
`
`
`[54] BIOERODABLE FILM FOR DELIVERY OF [54] BIOERODABLE FILM FOR DELIVERY OF [54] BIOERODABLE FILM FOR DELIVERY OF
`[54] BIOERODABLE FILM FOR DELIVERY OF
`
`
`PHARMACEUTICAL COMPOUNDS OF PHARMACEUTICAL COMPOUNDS OF PHARMACEUTICAL COMPOUNDS OF
`PHARMACEUTICAL COMPOUNDS ()1?
`MUCOS AL SURFACES
`
`
`MUCOSAL SURFACES MUCOSAL SURFACES MUCOSAL SURFACES
`
`
`
`[75] Inventors: Gilles H. Tapolsky; David W. [75] Inventors: Gilles H. Tapolsky; David W. [75] Inventors: Gilles H. Tapolsky; David W.
`
`Inventors: Gilles HI Osborne both of The Woodlands TeX. David WI
`
`
`
`Osborne, both of The Woodlands, Tex. Osborne, both of The Woodlands, Tex. Osborne, both of The Woodlands, Tex.
`’
`’
`631
`
`
`[73] Assignee: Virotex Corporation, The Woodlands, [73] Assignee: Virotex Corporation, The Woodlands, [73] Assignee: Virotex Corporation, The Woodlands,
`
`
`Tex. Tex. Tex.
`TeX-
`
`
`
`[21] Appl. No.: 09/144,827 [21] Appl. No.: 09/144,827 [21] Appl. No.: 09/144,827
`[21] App1_ NO; 09/144,827
`
`[22] Filed: (cid:9)[22] Filed: (cid:9)[22] Filed: (cid:9)
`
`
`[22] Filed:
`
`Sep. 1, 1998 Sep. 1, 1998 Sep. 1, 1998
`
`
`Sep. 1, 1998
`
`
`
`Related U.S. Application Data Related U.S. Application Data Related U.S. Application Data
`Related US, Application Data
`
`
`
`[63] Continuation of application No. 08/734,519, Oct. 18, 1996, [63] Continuation of application No. 08/734,519, Oct. 18, 1996, [63] Continuation of application No. 08/734,519, Oct. 18, 1996,
`[63] Continuation of application No. 08/734,519, Oct. 18, 1996,
`
`
`Pat. No. 5,800,832. Pat. No. 5,800,832. Pat. No. 5,800,832.
`Pat, NO, 5,800,832
`
`
`
` A61K 9/70; A61K 47/38; A61K 9/70; A61K 47/38; A61K 9/70; A61K 47/38;
`
`[51] Int. C1.7 (cid:9)[51] Int. C1.7 (cid:9)[51] Int. C1.7 (cid:9)
`Int. (:1.7 .......................... ..
`
`
`A61M 37/00 A61M 37/00 A61M 37/00
`A61M 37/00
`
`
` 424/449; 424/448; 424/434 424/449; 424/448; 424/434 424/449; 424/448; 424/434
`
`
`[52] U.S. Cl. (cid:9)[52] U.S. Cl. (cid:9)[52] U.S. Cl. (cid:9)
`[52] US. Cl. ......................... .. 424/449; 424/448; 424/434
`
`
`[58] Field of Search (cid:9)[58] Field of Search (cid:9)[58] Field of Search (cid:9)
`
`
` 424/449, 448, 424/449, 448, 424/449, 448,
`[58] Field of Search ................................... .. 424/449, 448,
`
`
`424/434 424/434 424/434
`424/434
`
`
`
`[56] [56] [56]
`[56]
`
`
`
`References Cited References Cited References Cited
`References Cited
`
`U.S. PATENT DOCUMENTS U.S. PATENT DOCUMENTS U.S. PATENT DOCUMENTS
`
`
`U-S- PATENT DOCUMENTS
`
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`
`
`
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`
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`
`
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`
`
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`
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`.. 424/19
`
`
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`
`
` 424/14 424/14 424/14
`4,250,163
`2/1981 Nflgai ct a1~
`-- 424/14
`
`
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`
`
` 424/148 424/148 424/148
`4,285,934
`8/1981 Tinnell ............ ..
`424/148
`
`
`4,286,592 9/1981 Chandrasekaran (cid:9)4,286,592 9/1981 Chandrasekaran (cid:9)4,286,592 9/1981 Chandrasekaran (cid:9)
`
`
` 128/260 128/260 128/260
`4,286,592
`9/1981 Chandrasekaran
`128/260
`
`
`4,292,299 9/1981 Suzuki (cid:9)4,292,299 9/1981 Suzuki (cid:9)4,292,299 9/1981 Suzuki (cid:9)
`
`
` 424/16 424/16 424/16
`4,292,299
`9/1981 Suzuki
`.. 424/16
`
`
`4,381,296 4/1983 Tinnell (cid:9)4,381,296 4/1983 Tinnell (cid:9)4,381,296 4/1983 Tinnell (cid:9)
`
`
` 424/148 424/148 424/148
`4,381,296
`4/1983 Tinnell ..... ..
`424/148
`
`
`4,517,173 5/1985 Kizawa et al. (cid:9)4,517,173 5/1985 Kizawa et al. (cid:9)4,517,173 5/1985 Kizawa et al. (cid:9)
`
`
` 424/16 424/16 424/16
`4,517,173
`5/1985 KiZaWa et al. .
`.. 424/16
`
`
`4,518,721 5/1985 Dhabhar et al. (cid:9)4,518,721 5/1985 Dhabhar et al. (cid:9)4,518,721 5/1985 Dhabhar et al. (cid:9)
`
`
` 523/120 523/120 523/120
`4,518,721
`5/1985 Dhabhar et al- --
`523/120
`
`
`4,572,832 2/1986 Kigasawa et al. (cid:9)4,572,832 2/1986 Kigasawa et al. (cid:9)4,572,832 2/1986 Kigasawa et al. (cid:9)
`
`
` 424/19 424/19 424/19
`4,572,832
`2/1986 Kigasawa et a1~
`-~ 424/19
`
`
`4,668,232 5/1987 Cordes et al. (cid:9)4,668,232 5/1987 Cordes et al. (cid:9)4,668,232 5/1987 Cordes et al. (cid:9)
`
`
` 604/897 604/897 604/897
`1;;
`go?flesldét ‘11' 1""
`
`
`4,713,243 12/1987 Schiraldi et al. (cid:9)4,713,243 12/1987 Schiraldi et al. (cid:9)4,713,243 12/1987 Schiraldi et al. (cid:9)
`
`
` 424/151 424/151 424/151
`’
`’
`.
`
`
`4,715,369 12/1987 Susuki et al. (cid:9)4,715,369 12/1987 Susuki et al. (cid:9)4,715,369 12/1987 Susuki et al. (cid:9)
`
`
` 128/156 128/156 128/156
`2:121:52?
`"""""""""" " 128/156
`
`
`4,720,387 1/1988 Sakamoto et al.. 4,720,387 1/1988 Sakamoto et al.. 4,720,387 1/1988 Sakamoto et al..
`4,740,365
`4/1988 Yukimatsu et al. ................... .. 424/435
`
`
`4,740,365 4/1988 Yukimatsu et al. (cid:9)4,740,365 4/1988 Yukimatsu et al. (cid:9)4,740,365 4/1988 Yukimatsu et al. (cid:9)
`
`
` 424/435 424/435 424/435
`
`
`4,765,983 8/1988 Takayanagi et al. (cid:9)4,765,983 8/1988 Takayanagi et al. (cid:9)4,765,983 8/1988 Takayanagi et al. (cid:9)
`
`
` 424/434 424/434 424/434
`4,765,983
`8/1988 Takayanagi et al. .
`424/434
`
`
`4,867,970 9/1989 Newsham et al. (cid:9)4,867,970 9/1989 Newsham et al. (cid:9)4,867,970 9/1989 Newsham et al. (cid:9)
`
`
` 424/81 424/81 424/81
`4,867,970
`9/1989 Newsham et al. ...................... .. 424/81
`
`Cll‘a 1ea..
`
`
`
`6,159,498 6,159,498 6,159,498
`6,159,498
`
`
`Dec. 12, 2000 Dec. 12, 2000 Dec. 12, 2000
`Dec. 12, 2000
`
`
`
`
`4,889,720 12/1989 Konishi (cid:9)4,889,720 12/1989 Konishi (cid:9)4,889,720 12/1989 Konishi (cid:9)
`
` 424/448 424/448 424/448
`4,889,720 12/1989 Konishi ................................. .. 424/448
`
`
`4,894,232 4,894,232 4,894,232
`
`
`1/1990 Reul et al. (cid:9)1/1990 Reul et al. (cid:9)1/1990 Reul et al. (cid:9)
`
`
` 424/439 424/439 424/439
`4,894,232
`1/1990 Reul et al. ' ........ ..
`.. 424/439
`
`
`2/1990 Yanagibashi et al. (cid:9)2/1990 Yanagibashi et al. (cid:9)2/1990 Yanagibashi et al. (cid:9)
`
`
` 424/448 424/448 424/448
`
`
`4,900,554 4,900,554 4,900,554
`4,900,554
`2/1990 Yanagibashi et al.
`.. 424/448
`
`
`4,906,463 4,906,463 4,906,463
`
`
`3/1990 Cleary et al. (cid:9)3/1990 Cleary et al. (cid:9)3/1990 Cleary et al. (cid:9)
`
`
` 424/78 424/78 424/78
`4,906,463
`3/1990 Cleary et al. ........................... .. 424/78
`
`
`4,915,948 4,915,948 4,915,948
`
`
`4/1990 Gallopo et al. (cid:9)4/1990 Gallopo et al. (cid:9)4/1990 Gallopo et al. (cid:9)
`
`
` 424/435 424/435 424/435
`4’990’339
`
`Gallopo et al. ....................... .. 2/1991 sc.hull et a1‘ '
`
`
`4,990,339 4,990,339 4,990,339
`
`
`2/1991 Schull et al. . 2/1991 Schull et al. . 2/1991 Schull et al. .
`
`
`5,059,189 10/1991 Cilento et al. (cid:9)5,059,189 10/1991 Cilento et al. (cid:9)5,059,189 10/1991 Cilento et al. (cid:9)
`
`
` 604/307 604/307 604/307
`5,059,189 10/1991 Cilento et al. ........................ .. 604/307
`
`
`5,064,654 11/1991 Berner et al. (cid:9)5,064,654 11/1991 Berner et al. (cid:9)5,064,654 11/1991 Berner et al. (cid:9)
`
`
` 424/448 424/448 424/448
`2124a
`
`
`5,081,157 5,081,157 5,081,157
`
`
`1/1992 Pomerantz (cid:9)1/1992 Pomerantz (cid:9)1/1992 Pomerantz (cid:9)
`
`
` 514/781 514/781 514/781
`
`
`5,081,158 5,081,158 5,081,158
`
`
`1/1992 Pomerantz (cid:9)1/1992 Pomerantz (cid:9)1/1992 Pomerantz (cid:9)
`
`
` 514/781 514/781 514/781
`5,081,158
`1/1992 PomerantZ
`514/781
`
`
`5,116,621 5,116,621 5,116,621
`
`
`5/1992 Oji et al. (cid:9)5/1992 Oji et al. (cid:9)5/1992 Oji et al. (cid:9)
`
`
` 424/445 424/445 424/445
`5,116,621
`5/1992 Oji et al.
`.. 424/445
`
`
`8/1992 Kuroya et al. (cid:9)8/1992 Kuroya et al. (cid:9)8/1992 Kuroya et al. (cid:9)
`
`
` 424/435 424/435 424/435
`
`
`5,137,729 5,137,729 5,137,729
`5,137,729
`8/1992 Kuroya et al. ........................ .. 424/435
`
`
`5,192,802 5,192,802 5,192,802
`
`
`3/1993 Rencher (cid:9)3/1993 Rencher (cid:9)3/1993 Rencher (cid:9)
`
`
` 514/535 514/535 514/535
`5,192,802
`3/1993 Rencher ................................ .. 514/535
`
`
`5,196,202 5,196,202 5,196,202
`
`
`3/1993 Konishi (cid:9)3/1993 Konishi (cid:9)3/1993 Konishi (cid:9)
`
`
` 424/448 424/448 424/448
`5,196,202
`3/1993 Konishi ...... ..
`.. 424/448
`
`
`5,298,258 5,298,258 5,298,258
`
`
`3/1994 Akemi et al. (cid:9)3/1994 Akemi et al. (cid:9)3/1994 Akemi et al. (cid:9)
`
`
` 424/484 424/484 424/484
`5,298,258
`3/1994 Akemietal.
`.. 424/484
`
`
`5,314,915 5,314,915 5,314,915
`
`
`5/1994 Rencher (cid:9)5/1994 Rencher (cid:9)5/1994 Rencher (cid:9)
`
`
` 514/535 514/535 514/535
`5,314,915
`5/1994 Rencher ................................ .. 514/535
`
`
`5,332,576 5,332,576 5,332,576
`
`
`7/1994 Mantelle (cid:9)7/1994 Mantelle (cid:9)7/1994 Mantelle (cid:9)
`
`
` 424/443 424/443 424/443
`5,332,576
`7/1994 Mantelle ............................... .. 424/443
`
`
`5,462,749 10/1995 Rencher (cid:9)5,462,749 10/1995 Rencher (cid:9)5,462,749 10/1995 Rencher (cid:9)
`
`
` 424/484 424/484 424/484
`5,462,749 10/1995 Rencher ~~~~~ -~
`-~ 424/484
`
`
`5,466,465 11/1995 Royds et al. (cid:9)5,466,465 11/1995 Royds et al. (cid:9)5,466,465 11/1995 Royds et al. (cid:9)
`
`
` 424/449 424/449 424/449
`5,466,465 11/1995 Royds et al. .
`.. 424/449
`
`
`5,505,956 5,505,956 5,505,956
`
`
`4/1996 Kim et al. (cid:9)4/1996 Kim et al. (cid:9)4/1996 Kim et al. (cid:9)
`
`
` 424/448 424/448 424/448
`5,505,956
`4/1996 Kim et al. ............................. .. 424/448
`
`
`5,780,047 5,780,047 5,780,047
`
`
`7/1998 Kamiya et al. . 7/1998 Kamiya et al. . 7/1998 Kamiya et al. .
`577807047
`7/1998 Kamiya et aL _
`
`FOREIGN PATENT DOCUMENTS FOREIGN PATENT DOCUMENTS FOREIGN PATENT DOCUMENTS
`
`
`FOREIGN PATENT DOCUMENTS
`
`
`0050480 4/1982 European Pat. Off.. 0050480 4/1982 European Pat. Off.. 0050480 4/1982 European Pat. Off..
`0050480 4/1982 European Pat~ Om _
`
`
`0250187 12/1987 European Pat. Off.. 0250187 12/1987 European Pat. Off.. 0250187 12/1987 European Pat. Off..
`0250187 12/1987 European Pat. Off. .
`
`
`0381194 8/1990 European Pat. Off.. 0381194 8/1990 European Pat. Off.. 0381194 8/1990 European Pat. Off..
`0381194 8/1990 European Pat. Off. .
`
`
`0781546 7/1997 European Pat. Off.. 0781546 7/1997 European Pat. Off.. 0781546 7/1997 European Pat. Off..
`0781546 7/1997 European Pat. Off. .
`
`
`2497098 7/1982 France . 2497098 7/1982 France . 2497098 7/1982 France .
`2497098 7/1982 France .
`
`
`2582942 12/1986 France . 2582942 12/1986 France . 2582942 12/1986 France .
`2582942 12/1986 France .
`
`
`56/100714 8/1981 Japan . 56/100714 8/1981 Japan . 56/100714 8/1981 Japan .
`56612323): 13%;;
`I
`
`
`0159604 10/1985 Japan . 0159604 10/1985 Japan . 0159604 10/1985 Japan .
`0262422 4/1988 Japan‘
`
`
`0262422 4/1988 Japan . 0262422 4/1988 Japan . 0262422 4/1988 Japan .
`
`
`
`Primary Examiner—Edward J. Webman Primary Examiner—Edward J. Webman Primary Examiner—Edward J. Webman
`Primary Examiner—EdWard J. Webman
`
`
`Attorney, Agent, or Firm—Morrison & Foerster LLP Attorney, Agent, or Firm—Morrison & Foerster LLP Attorney, Agent, or Firm—Morrison & Foerster LLP
`Attorney) Agent) Or Firm_MOrriSOn & Foerster LLP
`
`
`
`[57] (cid:9)[57] (cid:9)[57] (cid:9)
`[57]
`
`
`
`ABSTRACT ABSTRACT ABSTRACT
`ABSTRACT
`
`
`
`The present invention relates to water-soluble, bioerodable The present invention relates to water-soluble, bioerodable The present invention relates to water-soluble, bioerodable
`The present invention relates to Water-soluble, bioerodable
`
`
`pharmaceutical delivery device for application to mucosal pharmaceutical delivery device for application to mucosal pharmaceutical delivery device for application to mucosal
`pharmaceutical delivery device for application to mucosal
`
`
`surfaces. The device comprises an adhesive layer and a surfaces. The device comprises an adhesive layer and a surfaces. The device comprises an adhesive layer and a
`surfaces. The device comprises an adhesive layer and a
`non-adhesive backing layer, and the pharmaceutical may be
`
`
`non-adhesive backing layer, and the pharmaceutical may be non-adhesive backing layer, and the pharmaceutical may be non-adhesive backing layer, and the pharmaceutical may be
`
`
`provided in either or both layers. Upon application, the provided in either or both layers. Upon application, the provided in either or both layers. Upon application, the
`provided in either or both layers. Upon application, the
`device adheres to 'the mucosal surface,' providing drug
`
`
`device adheres to the mucosal surface, providing drug device adheres to the mucosal surface, providing drug device adheres to the mucosal surface, providing drug
`
`
`delivery and protection to the treatment site. delivery and protection to the treatment site. delivery and protection to the treatment site.
`dehvery and Protecnon to the treatment Sne
`
`'
`
`'
`
`'
`
`'
`
`'
`
`27 Claims, No Drawings 27 Claims, No Drawings 27 Claims, No Drawings
`
`
`27 Claims, N0 Drawings
`
`MYLAN - EXHIBIT 1012
`
`(cid:9)
`(cid:9)
`(cid:9)
`

`
`6,159,498
`6,159,498 6,159,498 6,159,498
`
`
`
`
`
`
`
`1
`
`
`1 1 1
`BIOERODABLE FILM FOR DELIVERY OF
`
`
`BIOERODABLE FILM FOR DELIVERY OF BIOERODABLE FILM FOR DELIVERY OF BIOERODABLE FILM FOR DELIVERY OF
`PHARMACEUTICAL COMPOUNDS OF
`
`
`PHARMACEUTICAL COMPOUNDS OF PHARMACEUTICAL COMPOUNDS OF PHARMACEUTICAL COMPOUNDS OF
`MUCOSAL SURFACES
`
`
`MUCOSAL SURFACES MUCOSAL SURFACES MUCOSAL SURFACES
`
`
`
`This is a continuation of application Ser. No. 08/734,519 This is a continuation of application Ser. No. 08/734,519 This is a continuation of application Ser. No. 08/734,519
`This is a continuation of application Ser. No. 08/734,519
`
`
`filed Oct. 18, 1996, now U.S. Pat. No. 5,800,832. filed Oct. 18, 1996, now U.S. Pat. No. 5,800,832. filed Oct. 18, 1996, now U.S. Pat. No. 5,800,832.
`?led Oct. 18, 1996, now US. Pat. No. 5,800,832.
`
`
`FIELD OF THE INVENTION FIELD OF THE INVENTION FIELD OF THE INVENTION
`FIELD OF THE INVENTION
`
`
`The present invention relates generally to a bioerodable, The present invention relates generally to a bioerodable, The present invention relates generally to a bioerodable,
`The present invention relates generally to a bioerodable,
`Water-soluble pharmaceutical carrier Which adheres to
`
`
`water-soluble pharmaceutical carrier which adheres to water-soluble pharmaceutical carrier which adheres to water-soluble pharmaceutical carrier which adheres to
`mucosal surfaces for the localized delivery of pharmaceu
`
`
`mucosal surfaces for the localized delivery of pharmaceu-mucosal surfaces for the localized delivery of pharmaceu-mucosal surfaces for the localized delivery of pharmaceu-
`tical compounds and protection of the treatment site.
`
`
`tical compounds and protection of the treatment site. tical compounds and protection of the treatment site. tical compounds and protection of the treatment site.
`
`
`BACKGROUND OF THE INVENTION BACKGROUND OF THE INVENTION BACKGROUND OF THE INVENTION
`BACKGROUND OF THE INVENTION
`The localiZed treatment of body tissues, diseases, and
`
`
`The localized treatment of body tissues, diseases, and The localized treatment of body tissues, diseases, and The localized treatment of body tissues, diseases, and
`Wounds requires that the particular pharmaceutical compo
`
`
`wounds requires that the particular pharmaceutical compo-wounds requires that the particular pharmaceutical compo-wounds requires that the particular pharmaceutical compo-
`
`
`nent be maintained at the site of treatment for an effective nent be maintained at the site of treatment for an effective nent be maintained at the site of treatment for an effective
`nent be maintained at the site of treatment for an effective
`period of time. Given the tendency of natural bodily ?uids
`
`
`period of time. Given the tendency of natural bodily fluids period of time. Given the tendency of natural bodily fluids period of time. Given the tendency of natural bodily fluids
`to rapidly Wash aWay topically applied pharmaceutical
`
`
`to rapidly wash away topically applied pharmaceutical to rapidly wash away topically applied pharmaceutical to rapidly wash away topically applied pharmaceutical
`components, the topical treatment of Wet mucosal tissues
`
`
`components, the topical treatment of wet mucosal tissues components, the topical treatment of wet mucosal tissues components, the topical treatment of wet mucosal tissues
`has been problematic. In the mouth, saliva, natural replace
`
`
`has been problematic. In the mouth, saliva, natural replace-has been problematic. In the mouth, saliva, natural replace-has been problematic. In the mouth, saliva, natural replace-
`ment of the mucosal tissue, and eating, drinking, and speak
`
`
`ment of the mucosal tissue, and eating, drinking, and speak-ment of the mucosal tissue, and eating, drinking, and speak-ment of the mucosal tissue, and eating, drinking, and speak-
`
`
`ing movements are some of the problems that have limited ing movements are some of the problems that have limited ing movements are some of the problems that have limited
`ing movements are some of the problems that have limited
`
`
`the effectiveness and residence time of pharmaceutical car-the effectiveness and residence time of pharmaceutical car-the effectiveness and residence time of pharmaceutical car-
`the effectiveness and residence time of pharmaceutical car
`
`
`riers. riers. riers.
`riers.
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`
`Bioadhesive carriers are known in the art and include gels, Bioadhesive carriers are known in the art and include gels, Bioadhesive carriers are known in the art and include gels,
`Bioadhesive carriers are knoWn in the art and include gels,
`pastes, tablets, and ?lms. These products, hoWever, may lack
`
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`pastes, tablets, and films. These products, however, may lack pastes, tablets, and films. These products, however, may lack pastes, tablets, and films. These products, however, may lack
`
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`one or several of the preferred characteristic for an efficient one or several of the preferred characteristic for an efficient one or several of the preferred characteristic for an efficient
`one or several of the preferred characteristic for an ef?cient
`and commercially acceptable pharmaceutical delivery
`
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`and commercially acceptable pharmaceutical delivery and commercially acceptable pharmaceutical delivery and commercially acceptable pharmaceutical delivery
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`device. Some characteristics which are preferred by users of device. Some characteristics which are preferred by users of device. Some characteristics which are preferred by users of
`device. Some characteristics Which are preferred by users of
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`
`bioadhesive carriers include water-erodability, ease of han-bioadhesive carriers include water-erodability, ease of han-bioadhesive carriers include water-erodability, ease of han-
`bioadhesive carriers include Water-erodability, ease of han
`
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`dling and application to the treatment site, and ease of dling and application to the treatment site, and ease of dling and application to the treatment site, and ease of
`dling and application to the treatment site, and ease of
`comfort With minimal foreign body sensation. Other pre
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`comfort with minimal foreign body sensation. Other pre-comfort with minimal foreign body sensation. Other pre-comfort with minimal foreign body sensation. Other pre-
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`ferred characteristics for an effective and user-friendly prod-ferred characteristics for an effective and user-friendly prod-ferred characteristics for an effective and user-friendly prod-
`ferred characteristics for an effective and user-friendly prod
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`uct for the treatment of mucosal surfaces include the use of uct for the treatment of mucosal surfaces include the use of uct for the treatment of mucosal surfaces include the use of
`uct for the treatment of mucosal surfaces include the use of
`pharmaceutically approved components or materials; instan
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`pharmaceutically approved components or materials; instan-pharmaceutically approved components or materials; instan-pharmaceutically approved components or materials; instan-
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`taneous adhesion to mucosal surface upon application; taneous adhesion to mucosal surface upon application; taneous adhesion to mucosal surface upon application;
`taneous adhesion to mucosal surface upon application;
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`increased residence time for the protection of the affected increased residence time for the protection of the affected increased residence time for the protection of the affected
`increased residence time for the protection of the affected
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`tissue or the delivery of the pharmaceutical component; and tissue or the delivery of the pharmaceutical component; and tissue or the delivery of the pharmaceutical component; and
`tissue or the delivery of the pharmaceutical component; and
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`ease of removal of the delivery device from the affected ease of removal of the delivery device from the affected ease of removal of the delivery device from the affected
`ease of removal of the delivery device from the affected
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`tissue or natural dissolution of the delivery device at the tissue or natural dissolution of the delivery device at the tissue or natural dissolution of the delivery device at the
`tissue or natural dissolution of the delivery device at the
`delivery site.
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`delivery site. delivery site. delivery site.
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`
`Bioadhesive gels which are used for application to Bioadhesive gels which are used for application to Bioadhesive gels which are used for application to
`Bioadhesive gels Which are used for application to
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`mucosal tissues and especially the oral cavity are known in mucosal tissues and especially the oral cavity are known in mucosal tissues and especially the oral cavity are known in
`mucosal tissues and especially the oral cavity are knoWn in
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`the art. For example, U.S. Pat. No. 5,192,802 describes a the art. For example, U.S. Pat. No. 5,192,802 describes a the art. For example, U.S. Pat. No. 5,192,802 describes a
`the art. For example, US. Pat. No. 5,192,802 describes a
`
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`bioadhesive teething gel made from a blend of sodium bioadhesive teething gel made from a blend of sodium bioadhesive teething gel made from a blend of sodium
`bioadhesive teething gel made from a blend of sodium
`carboxymethyl cellulose and xantham gum. The gel may
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`carboxymethyl cellulose and xantham gum. The gel may carboxymethyl cellulose and xantham gum. The gel may carboxymethyl cellulose and xantham gum. The gel may
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`also have potential use in the treatment of canker sores, fever also have potential use in the treatment of canker sores, fever also have potential use in the treatment of canker sores, fever
`also have potential use in the treatment of canker sores, fever
`blisters, and hemorrhoids. HoWever, this type of pharma
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`blisters, and hemorrhoids. However, this type of pharma-blisters, and hemorrhoids. However, this type of pharma-blisters, and hemorrhoids. However, this type of pharma-
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`ceutical carrier has a very limited residence time, given that ceutical carrier has a very limited residence time, given that ceutical carrier has a very limited residence time, given that
`ceutical carrier has a very limited residence time, given that
`
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`body fluids such as saliva quickly wash it away from the body fluids such as saliva quickly wash it away from the body fluids such as saliva quickly wash it away from the
`body ?uids such as saliva quickly Wash it aWay from the
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`treatment site. Bioadhesive gels are also described in U.S. treatment site. Bioadhesive gels are also described in U.S. treatment site. Bioadhesive gels are also described in U.S.
`treatment site. Bioadhesive gels are also described in US.
`
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`Pat. Nos. 5,314,915; 5,298,258; and 5,642,749. The gels Pat. Nos. 5,314,915; 5,298,258; and 5,642,749. The gels Pat. Nos. 5,314,915; 5,298,258; and 5,642,749. The gels
`Pat. Nos. 5,314,915; 5,298,258; and 5,642,749. The gels
`
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`described in those patents use an aqueous or oily medium described in those patents use an aqueous or oily medium described in those patents use an aqueous or oily medium
`described in those patents use an aqueous or oily medium
`and different types of bioadhesive and gelling agents.
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`and different types of bioadhesive and gelling agents. and different types of bioadhesive and gelling agents. and different types of bioadhesive and gelling agents.
`
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`Denture adhesive pastes are another type of bioadhesive Denture adhesive pastes are another type of bioadhesive Denture adhesive pastes are another type of bioadhesive
`Denture adhesive pastes are another type of bioadhesive
`
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`product known in the art. However, these preparations are product known in the art. However, these preparations are product known in the art. However, these preparations are
`product knoWn in the art. HoWever, these preparations are
`used primarily for their adhesive properties, to adhere den
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`used primarily for their adhesive properties, to adhere den-used primarily for their adhesive properties, to adhere den-used primarily for their adhesive properties, to adhere den-
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`tures to the gums, rather than for the protection of tissue or tures to the gums, rather than for the protection of tissue or tures to the gums, rather than for the protection of tissue or
`tures to the gums, rather than for the protection of tissue or
`for the topical delivery of pharmaceuticals, although drugs
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`for the topical delivery of pharmaceuticals, although drugs for the topical delivery of pharmaceuticals, although drugs for the topical delivery of pharmaceuticals, although drugs
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`such as local anesthetics may be used in the paste for the such as local anesthetics may be used in the paste for the such as local anesthetics may be used in the paste for the
`such as local anesthetics may be used in the paste for the
`
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`relief of sore gums. U.S. Pat. Nos. 4,894,232 and 4,518,721 relief of sore gums. U.S. Pat. Nos. 4,894,232 and 4,518,721 relief of sore gums. U.S. Pat. Nos. 4,894,232 and 4,518,721
`relief of sore gums. US. Pat. Nos. 4,894,232 and 4,518,721
`
`
`describe denture adhesive pastes. The '721 Patent describes describe denture adhesive pastes. The '721 Patent describes describe denture adhesive pastes. The '721 Patent describes
`describe denture adhesive pastes. The ’721 Patent describes
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`a combination of sodium carboxymethyl cellulose and poly-a combination of sodium carboxymethyl cellulose and poly-a combination of sodium carboxymethyl cellulose and poly-
`a combination of sodium carboxymethyl cellulose and poly
`ethylene oxide in polyethylene glycol.
`
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`ethylene oxide in polyethylene glycol. ethylene oxide in polyethylene glycol. ethylene oxide in polyethylene glycol.
`
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`Pastes have also been used as film protectants and as drug Pastes have also been used as film protectants and as drug Pastes have also been used as film protectants and as drug
`Pastes have also been used as ?lm protectants and as drug
`delivery systems. One such example having ?lm forming
`
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`delivery systems. One such example having film forming delivery systems. One such example having film forming delivery systems. One such example having film forming
`
`5 5 5
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`25 25 25
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`25
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`2
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`2 2 2
`and adhesive properties is the product commercialiZed under
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`and adhesive properties is the product commercialized under and adhesive properties is the product commercialized under and adhesive properties is the product commercialized under
`
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`the name Orabase®-B, which is a thick gel or paste for the the name Orabase®-B, which is a thick gel or paste for the the name Orabase®-B, which is a thick gel or paste for the
`the name Orabase®-B, Which is a thick gel or paste for the
`
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`relief of mouth sores. Ingredients include guar gum, sodium relief of mouth sores. Ingredients include guar gum, sodium relief of mouth sores. Ingredients include guar gum, sodium
`relief of mouth sores. Ingredients include guar gum, sodium
`carboxymethyl cellulose, tragacanth gum, and pectin. Even
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`carboxymethyl cellulose, tragacanth gum, and pectin. Even carboxymethyl cellulose, tragacanth gum, and pectin. Even carboxymethyl cellulose, tragacanth gum, and pectin. Even
`though it does provide numbing to the area of application,
`
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`though it does provide numbing to the area of application, though it does provide numbing to the area of application, though it does provide numbing to the area of application,
`the ?lm forming behavior and bioadhesion do not last. Thus,
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`the film forming behavior and bioadhesion do not last. Thus, the film forming behavior and bioadhesion do not last. Thus, the film forming behavior and bioadhesion do not last. Thus,
`
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`this product has a limited residence time. this product has a limited residence time. this product has a limited residence time.
`this product has a limited residence time.
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`Bioadhesive tablets are described in U.S. Pat. No. 4,915, Bioadhesive tablets are described in U.S. Pat. No. 4,915, Bioadhesive tablets are described in U.S. Pat. No. 4,915,
`Bioadhesive tablets are described in US. Pat. No. 4,915,
`
`
`948. The water-soluble bioadhesive material used in this 948. The water-soluble bioadhesive material used in this 948. The water-soluble bioadhesive material used in this
`948. The Water-soluble bioadhesive material used in this
`
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`10 device is a xanthan gum or a pectin combined with an 10 device is a xanthan gum or a pectin combined with an 10 device is a xanthan gum or a pectin combined with an
`device is a xanthan gum or a pectin combined With an
`10
`adhesion enhancing material such as a polyol. Although
`
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`adhesion enhancing material such as a polyol. Although adhesion enhancing material such as a polyol. Although adhesion enhancing material such as a polyol. Although
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`residence time is improved with the use of bioadhesive residence time is improved with the use of bioadhesive residence time is improved with the use of bioadhesive
`residence time is improved With the use of bioadhesive
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`tablets, they are not user friendly, especially when used in tablets, they are not user friendly, especially when used in tablets, they are not user friendly, especially when used in
`tablets, they are not user friendly, especially When used in
`the oral cavity, given the unpleasant feelings associated With
`
`
`the oral cavity, given the unpleasant feelings associated with the oral cavity, given the unpleasant feelings associated with the oral cavity, given the unpleasant feelings associated with
`their solidity, bulkiness, and sloW dissolution time. Bioad
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`is their solidity, bulkiness, and slow dissolution time. Bioad-is their solidity, bulkiness, and slow dissolution time. Bioad-is their solidity, bulkiness, and slow dissolution time. Bioad-
`15
`
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`hesive tablets are also described in U.S. Pat. Nos. 4,226,848; hesive tablets are also described in U.S. Pat. Nos. 4,226,848; hesive tablets are also described in U.S. Pat. Nos. 4,226,848;
`hesive tablets are also described in US. Pat. Nos. 4,226,848;
`
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`4,292,299; and 4,250,163, and are single layer or bilayer 4,292,299; and 4,250,163, and are single layer or bilayer 4,292,299; and 4,250,163, and are single layer or bilayer
`4,292,299; and 4,250,163, and are single layer or bilayer
`
`
`devices having an average thickness of 0.2 to 2.5 mm. The devices having an average thickness of 0.2 to 2.5 mm. The devices having an average thickness of 0.2 to 2.5 mm. The
`devices having an average thickness of 0.2 to 2.5 mm. The
`
`
`bioadhesive tablets described in these patents utilize a bioadhesive tablets described in these patents utilize a bioadhesive tablets described in these patents utilize a
`bioadhesive tablets described in these patents utiliZe a
`
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`20 non-adhesive component such as cellulose ether, a bioad-20 non-adhesive component such as cellulose ether, a bioad-20 non-adhesive component such as cellulose ether, a bioad-
`non-adhesive component such as cellulose ether, a bioad
`20
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`hesive component such as polyacrylic acid, sodium car-hesive c