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:
`
`6,159,498
`6,159,498
`6,159,498
`6,159,498
`Dec. 12, 2000
`Dec. 12, 2000
`Dec. 12, 2000
`Dec. 12, 2000
`
`.
`
`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;
`[51] Int. C1.7 (cid:9)
` A61K 9/70; A61K 47/38;
`[51] Int. C1.7 (cid:9)
` A61K 9/70; A61K 47/38;
`[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
`[52] U.S. Cl. (cid:9)
` 424/449; 424/448; 424/434
`[52] U.S. Cl. (cid:9)
` 424/449; 424/448; 424/434
`[52] U.S. Cl. (cid:9)
`[52] US. Cl. ......................... .. 424/449; 424/448; 424/434
`[58] Field of Search (cid:9)
` 424/449, 448,
`[58] Field of Search (cid:9)
` 424/449, 448,
`[58] Field of Search (cid:9)
` 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
`
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`U.S. PATENT DOCUMENTS
`U-S- PATENT DOCUMENTS
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` 106/170
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` 106/170
`3,640,741 2/1972 Etes (cid:9)
`3,996,934 12/1976 Zaffaroni (cid:9)
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` 128/268
`3,996,934 12/1976 Zaffaroni (cid:9)
` 128/268
`3,996,934 12/1976 Zaffaroni
`128/268
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` 424/19
`4,226,848 10/1980 Nagai et al. (cid:9)
` 424/19
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` 424/19
`4,226,848 10/1980 Nagai et al.
`.. 424/19
`4,250,163 2/1981 Nagai et al. (cid:9)
` 424/14
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` 424/14
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` 424/14
`4,250,163
`2/1981 Nflgai ct a1~
`-- 424/14
`4,285,934 8/1981 Tinnell (cid:9)
` 424/148
`4,285,934 8/1981 Tinnell (cid:9)
` 424/148
`4,285,934 8/1981 Tinnell (cid:9)
` 424/148
`4,285,934
`8/1981 Tinnell ............ ..
`424/148
`4,286,592 9/1981 Chandrasekaran (cid:9)
` 128/260
`4,286,592 9/1981 Chandrasekaran (cid:9)
` 128/260
`4,286,592 9/1981 Chandrasekaran (cid:9)
` 128/260
`4,286,592
`9/1981 Chandrasekaran
`128/260
`4,292,299 9/1981 Suzuki (cid:9)
` 424/16
`4,292,299 9/1981 Suzuki (cid:9)
` 424/16
`4,292,299 9/1981 Suzuki (cid:9)
` 424/16
`4,292,299
`9/1981 Suzuki
`.. 424/16
`4,381,296 4/1983 Tinnell (cid:9)
` 424/148
`4,381,296 4/1983 Tinnell (cid:9)
` 424/148
`4,381,296 4/1983 Tinnell (cid:9)
` 424/148
`4,381,296
`4/1983 Tinnell ..... ..
`424/148
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` 424/16
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` 424/16
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` 424/16
`4,517,173
`5/1985 KiZaWa et al. .
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`4,518,721 5/1985 Dhabhar et al. (cid:9)
` 523/120
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` 523/120
`4,518,721 5/1985 Dhabhar et al. (cid:9)
` 523/120
`4,518,721
`5/1985 Dhabhar et al- --
`523/120
`4,572,832 2/1986 Kigasawa et al. (cid:9)
` 424/19
`4,572,832 2/1986 Kigasawa et al. (cid:9)
` 424/19
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` 424/19
`4,572,832
`2/1986 Kigasawa et a1~
`-~ 424/19
`4,668,232 5/1987 Cordes et al. (cid:9)
` 604/897
`4,668,232 5/1987 Cordes et al. (cid:9)
` 604/897
`4,668,232 5/1987 Cordes et al. (cid:9)
` 604/897
`1;;
`go?flesldét ‘11' 1""
`4,713,243 12/1987 Schiraldi et al. (cid:9)
` 424/151
`4,713,243 12/1987 Schiraldi et al. (cid:9)
` 424/151
`4,713,243 12/1987 Schiraldi et al. (cid:9)
` 424/151
`’
`’
`.
`4,715,369 12/1987 Susuki et al. (cid:9)
` 128/156
`4,715,369 12/1987 Susuki et al. (cid:9)
` 128/156
`4,715,369 12/1987 Susuki et al. (cid:9)
` 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)
` 424/435
`4,740,365 4/1988 Yukimatsu et al. (cid:9)
` 424/435
`4,740,365 4/1988 Yukimatsu et al. (cid:9)
` 424/435
`4,765,983 8/1988 Takayanagi et al. (cid:9)
` 424/434
`4,765,983 8/1988 Takayanagi et al. (cid:9)
` 424/434
`4,765,983 8/1988 Takayanagi et al. (cid:9)
` 424/434
`4,765,983
`8/1988 Takayanagi et al. .
`424/434
`4,867,970 9/1989 Newsham et al. (cid:9)
` 424/81
`4,867,970 9/1989 Newsham et al. (cid:9)
` 424/81
`4,867,970 9/1989 Newsham et al. (cid:9)
` 424/81
`4,867,970
`9/1989 Newsham et al. ...................... .. 424/81
`
`Cll‘a 1ea..
`
` 424/448
`4,889,720 12/1989 Konishi (cid:9)
` 424/448
`4,889,720 12/1989 Konishi (cid:9)
` 424/448
`4,889,720 12/1989 Konishi (cid:9)
`4,889,720 12/1989 Konishi ................................. .. 424/448
`4,894,232
`1/1990 Reul et al. (cid:9)
` 424/439
`4,894,232
`1/1990 Reul et al. (cid:9)
` 424/439
`4,894,232
`1/1990 Reul et al. (cid:9)
` 424/439
`4,894,232
`1/1990 Reul et al. ' ........ ..
`.. 424/439
`2/1990 Yanagibashi et al. (cid:9)
` 424/448
`2/1990 Yanagibashi et al. (cid:9)
` 424/448
`2/1990 Yanagibashi et al. (cid:9)
` 424/448
`4,900,554
`4,900,554
`4,900,554
`4,900,554
`2/1990 Yanagibashi et al.
`.. 424/448
`4,906,463
`3/1990 Cleary et al. (cid:9)
` 424/78
`4,906,463
`3/1990 Cleary et al. (cid:9)
` 424/78
`4,906,463
`3/1990 Cleary et al. (cid:9)
` 424/78
`4,906,463
`3/1990 Cleary et al. ........................... .. 424/78
`4,915,948
`4/1990 Gallopo et al. (cid:9)
` 424/435
`4,915,948
`4/1990 Gallopo et al. (cid:9)
` 424/435
`4,915,948
`4/1990 Gallopo et al. (cid:9)
` 424/435
`4’990’339
`
`Gallopo et al. ....................... .. 2/1991 sc.hull et a1‘ '
`4,990,339
`2/1991 Schull et al. .
`4,990,339
`2/1991 Schull et al. .
`4,990,339
`2/1991 Schull et al. .
`5,059,189 10/1991 Cilento et al. (cid:9)
` 604/307
`5,059,189 10/1991 Cilento et al. (cid:9)
` 604/307
`5,059,189 10/1991 Cilento et al. (cid:9)
` 604/307
`5,059,189 10/1991 Cilento et al. ........................ .. 604/307
`5,064,654 11/1991 Berner et al. (cid:9)
` 424/448
`5,064,654 11/1991 Berner et al. (cid:9)
` 424/448
`5,064,654 11/1991 Berner et al. (cid:9)
` 424/448
`2124a
`5,081,157
`1/1992 Pomerantz (cid:9)
` 514/781
`5,081,157
`1/1992 Pomerantz (cid:9)
` 514/781
`5,081,157
`1/1992 Pomerantz (cid:9)
` 514/781
`5,081,158
`1/1992 Pomerantz (cid:9)
` 514/781
`5,081,158
`1/1992 Pomerantz (cid:9)
` 514/781
`5,081,158
`1/1992 Pomerantz (cid:9)
` 514/781
`5,081,158
`1/1992 PomerantZ
`514/781
`5,116,621
`5/1992 Oji et al. (cid:9)
` 424/445
`5,116,621
`5/1992 Oji et al. (cid:9)
` 424/445
`5,116,621
`5/1992 Oji et al. (cid:9)
` 424/445
`5,116,621
`5/1992 Oji et al.
`.. 424/445
`8/1992 Kuroya et al. (cid:9)
` 424/435
`8/1992 Kuroya et al. (cid:9)
` 424/435
`8/1992 Kuroya et al. (cid:9)
` 424/435
`5,137,729
`5,137,729
`5,137,729
`5,137,729
`8/1992 Kuroya et al. ........................ .. 424/435
`5,192,802
`3/1993 Rencher (cid:9)
` 514/535
`5,192,802
`3/1993 Rencher (cid:9)
` 514/535
`5,192,802
`3/1993 Rencher (cid:9)
` 514/535
`5,192,802
`3/1993 Rencher ................................ .. 514/535
`5,196,202
`3/1993 Konishi (cid:9)
` 424/448
`5,196,202
`3/1993 Konishi (cid:9)
` 424/448
`5,196,202
`3/1993 Konishi (cid:9)
` 424/448
`5,196,202
`3/1993 Konishi ...... ..
`.. 424/448
`5,298,258
`3/1994 Akemi et al. (cid:9)
` 424/484
`5,298,258
`3/1994 Akemi et al. (cid:9)
` 424/484
`5,298,258
`3/1994 Akemi et al. (cid:9)
` 424/484
`5,298,258
`3/1994 Akemietal.
`.. 424/484
`5,314,915
`5/1994 Rencher (cid:9)
` 514/535
`5,314,915
`5/1994 Rencher (cid:9)
` 514/535
`5,314,915
`5/1994 Rencher (cid:9)
` 514/535
`5,314,915
`5/1994 Rencher ................................ .. 514/535
`5,332,576
`5,332,576
`5,332,576
`7/1994 Mantelle (cid:9)
` 424/443
`7/1994 Mantelle (cid:9)
` 424/443
`7/1994 Mantelle (cid:9)
` 424/443
`5,332,576
`7/1994 Mantelle ............................... .. 424/443
`5,462,749 10/1995 Rencher (cid:9)
` 424/484
`5,462,749 10/1995 Rencher (cid:9)
` 424/484
`5,462,749 10/1995 Rencher (cid:9)
` 424/484
`5,462,749 10/1995 Rencher ~~~~~ -~
`-~ 424/484
`5,466,465 11/1995 Royds et al. (cid:9)
` 424/449
`5,466,465 11/1995 Royds et al. (cid:9)
` 424/449
`5,466,465 11/1995 Royds et al. (cid:9)
` 424/449
`5,466,465 11/1995 Royds et al. .
`.. 424/449
`5,505,956
`4/1996 Kim et al. (cid:9)
` 424/448
`5,505,956
`4/1996 Kim et al. (cid:9)
` 424/448
`5,505,956
`4/1996 Kim et al. (cid:9)
` 424/448
`5,505,956
`4/1996 Kim et al. ............................. .. 424/448
`5,780,047
`7/1998 Kamiya et al. .
`5,780,047
`7/1998 Kamiya et al. .
`5,780,047
`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
`
`Par Pharm., Inc., et al.
`Exhibit 1012
`Page 001
`
`(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.
`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
`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
`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
`and commercially acceptable pharmaceutical delivery
`and commercially acceptable pharmaceutical delivery
`and commercially acceptable pharmaceutical delivery
`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
`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
`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
`comfort with minimal foreign body sensation. Other pre-
`comfort with minimal foreign body sensation. Other pre-
`comfort with minimal foreign body sensation. Other pre-
`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
`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
`pharmaceutically approved components or materials; instan-
`pharmaceutically approved components or materials; instan-
`pharmaceutically approved components or materials; instan-
`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;
`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
`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
`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
`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.
`delivery site.
`delivery site.
`delivery site.
`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
`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
`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
`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
`carboxymethyl cellulose and xantham gum. The gel may
`carboxymethyl cellulose and xantham gum. The gel may
`carboxymethyl cellulose and xantham gum. The gel may
`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
`blisters, and hemorrhoids. However, this type of pharma-
`blisters, and hemorrhoids. However, this type of pharma-
`blisters, and hemorrhoids. However, this type of pharma-
`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
`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
`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.
`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
`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.
`and different types of bioadhesive and gelling agents.
`and different types of bioadhesive and gelling agents.
`and different types of bioadhesive and gelling agents.
`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
`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
`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-
`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
`for the topical delivery of pharmaceuticals, although drugs
`for the topical delivery of pharmaceuticals, although drugs
`for the topical delivery of pharmaceuticals, although drugs
`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
`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
`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.
`ethylene oxide in polyethylene glycol.
`ethylene oxide in polyethylene glycol.
`ethylene oxide in polyethylene glycol.
`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
`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
`
`25
`25
`25
`25
`
`2
`2
`2
`2
`and adhesive properties is the product commercialiZed under
`and adhesive properties is the product commercialized under
`and adhesive properties is the product commercialized under
`and adhesive properties is the product commercialized under
`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
`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
`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,
`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,
`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,
`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.
`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
`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
`adhesion enhancing material such as a polyol. Although
`adhesion enhancing material such as a polyol. Although
`adhesion enhancing material such as a polyol. Although
`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
`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
`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
`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;
`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
`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
`hesive component such as polyacrylic acid, sodium c