Indian Patents. 251449:"MONO-OR MULTILAYER, FILM-SHAPED, PRESSURE-SENSITIVE-ADHESIVE PREPARATION"

Title of Invention	"MONO-OR MULTILAYER, FILM-SHAPED, PRESSURE-SENSITIVE-ADHESIVE PREPARATION"
Abstract	The present invention is related to a mono- or multilayer, film-shaped, pressure-sensitive-adhesive preparation for application in the oral region, and containing at least a layer containing a polymethyl vinyl ether-maleic acid anhydride copolymer; polyvinyl acetate; and at least one cosmetic or pharmaceutical active substance.

Full Text	Self-adhesive film for teeth The present invention relates to film-shaped preparations which are pressure-sensitive adhesive to teeth, gums or the oral mucosa and which are suitable for cosmetic or medical treatment of the teeth, especially the tooth necks, and of the gums. In addition, the present invention relates to a process for the manufacture of such film-shaped preparations Products for cleaning one's mouth and for active substance delivery having the form of pastes, creams or mouth rinses have long since been known and have been available on the market. These products include tooth pastes and creams which have a cleaning effect, protect against caries, are desensitizing, or have a bleaching effect. Also known are creams, gels and ointments that are applied in the oral region for treating local illnesses and disorders such as anti-inflammatory remedies, analgesic remedies and/or tonics For some years, film-shaped, flat-shaped or strip-shaped oral application forms, too, have been commercially available and are used for cosmetic or therapeutic purposes. These application forms include, for example, the Listerine Pocket-Paks® by Pfizer or the "Teeth Whitestrips" by Procter & Gamble. Such application forms are as a rule based on films made up of water-soluble polymers which on use disintegrate rather quickly and are therefore not suitable for a longer-lasting treatment. In addition, products are known that consist of several layers, such as those disclosed in US 6,582,708, which, In addition, products are known that consist of several layers, such as those disclosed in US 6,582,708, which, however, include only one flexible layer and which, due to their overall thickness of up to 3 mm, are disturbing and unpleasant in the mouth. The recipes and methods used in the manufacture of the known film-shaped application forms, for the most part, start from water or from water-containing alcoholic polymer solutions. A disadvantage here is that there are limitations to preparing a completely dissolved formulation of lipophile, poorly water-soluble active substances or of active substances that are sensitive to water. The object of the present invention was thus to provide a mono- or multilayered, water-soluble or at least partially water-swellable, film-shaped material which has good adhesion to teeth, gums or the oral mucosa, which is suitable as active substance carrier, and which does not already disintegrate within a few seconds. More particularly, the object is to provide a film-shaped material of the aforementioned type which enables administration of waterinsoluble or water-sensitive active substances. This object is achieved by providing a mono- or multilayered, pressure-sensitive-adhesive, film-shaped preparation which contains at least one polymethyl vinyl ether-maleic acid anhydride copolymer, polyvinyl acetate and/or at least one copolymer of the vinyl acetate with vinyl alcohol esters of fatty acids, as well as at least one cosmetic and/or pharmaceutically active substance. Preferably, the content of polymethyl vinyl ether-maleic acid anhydride copolymer in the film-shaped, pressure sensitive adhesive preparations is 5 to 35%-wt. The content of polyvinyl acetate and/or of the copolymer(s) of the vinyl acetate with vinyl alcohol esters of fatty acids in the film-shaped, pressure-sensitive-adhesive preparations preferably amounts to 4 to 35%-wt. The film-shaped, pressure-sensitive adhesive preparations in addition have a content of at least one cosmetic and/or pharmaceutical active substance which is determined by the nature of the illness or by the cosmetic needs. The active substance is preferably a poorly water-soluble active substance or a water-sensitive active substance. The term "poorly water-soluble active substances" is understood to mean such active substances as have a solubility in water of less than 1 g/1. These include, for example, griseofulvin, estradiol and vitamin D3. The water-sensitive active substances include those active substances, the aqueous solution of which looses more than 0.1% of its active substance content within 24 hours at room temperature due to decomposition of the active substance. The water-sensitive active substances include, for example, acetylsalicylic acid and iodine. In a particularly preferred embodiment, the film-shaped, pressure-sensitive adhesive preparation in addition contains carboxrymethyl cellulose and/or one of its salts. The content of carboxymethyl cellulose or of one of its salts in the preparation amounts to 5 to 35%-wt. To manufacture the film-shaped preparations, which are pressure-sensitive adhesive on teeth, gums or the oral mucosa, the various, water-soluble and/or water-swellable polymers are mixed with at least one active substance in solutions containing organic solvents as main component. This mixture is used to coat a substrate, and the coated substrate is dried, optionally by application of heat. The advantages of the invention arise especially where mixtures of polymethyl vinyl ether-maleic acid anhydride copolymers with polyvinyl acetate or the copolymers of the vinyl acetate with vinyl alcohol esters of fatty acids, are used. The content of polymethyl vinyl ether-maleic acid anhydride copolymer is preferably 5 to 35%-wt., and the content of polyvinyl acetate and/or the copolymer(s) of the vinyl acetate with vinyl alcohol esters of fatty acids is preferably 4 to 35%-wt., in each case relative to the solids content. The polymethyl vinyl ether-maleic acid anhydride copolymers sold under the name of "Gantrez®" by the firm of ISP, and the polyvinyl acetates or copolymers of the vinyl acetate with vinyl alcohol esters of fatty acids, designated as "VINNAPAS®", of the firm of Wacker Polymer Systems, Burghausen, have proved to be particularly suitable in accordance with the present invention. Any solvents which dissolve the polymethyl vinyl ethermaleic acid anhydride copolymers and polyvinyl acetate or copolymers of the vinyl acetate with vinyl alcohol esters of fatty acids may be used as the organic solvents which, in the method according to the invention, are contained in the solution as the main component thereof. Of these organic solvents, those are used with preference which also mix with water since by adding small amounts of water, e.g. of 1 to 5%-wt., the dissolving power for the polymers and the active substance/active substances can be adapted to the given requirements. Particular preference is given to those organic solvents which permit addition of the active substance dissolved in ethanol or in an ethanol-water mixture. The especially preferred organic solvent is selected from the group comprising methyl ethyl ketone, ethyl acetate, ethanol, acetone and mixtures thereof. The consistency and/or tackiness of the resultant filmshaped preparations can be adapted to the demands placed on the product by altering the mixing ratio of ethanol and methyl ethyl ketone. Solvent mixtures containing an ethanol portion of 5 to 20%-wt., relative to the total solvent, have proved advantageous. To manufacture a preferred embodiment enabling a particularly successful adhesion of the film-shaped preparations Multilayer/ pressure-sensitive-adhesive film-shaped preparations, with which it is possible to achieve, for example, an, improved adhesion of the preparation to teeth, can be prepared, for example, by hot lamination, by coating already existent layers with further solvent-containing compounds, as described hereinabove in connection with the manufacture of a monolayer film, or by other processes known to those skilled in the art. Pieces having a size appropriate to the respective given purposes are then punched out from the film or laminate. The process according to the present invention results in film-shaped preparations which adhere to teeth, gums or the oral mucosa, which do not already disintegrate within a few seconds, and by means of which water-insoluble and even water- sensitive active substances can be administered. These preparations may advantageously be utilised for medical or cosmetic treatments. Example: 5g of a 33.3% solution (%-wt.) of a vinyl acetate-based polymer in methyl ethyl ketone and 3 g of a 15% solution (%-wt.) of polymethyl vinyl ether-maleic acid anhydride (= copolymer of methyl vinyl ether and maleic acid anhydride) in ethyl acetate were added together and homogenised. This resulted in a solution which was spread at various coating thicknesses and, subsequently, dried. This yielded flexible films which adhered both to the oral mucosa and to the teeth. We Claim: 1. Mono- or multilayer, film-shaped, pressure-sensitive-adhesive preparation for application in the oral region, and containing at least a layer containing - a polymethyl vinyl ether-maleic acid anhydride co-polymer; polyvinyl acetate; and - at least one cosmetic or pharmaceutical active substance. 2. Preparation as claimed in claim 1, whereby the layer additionally contains a copolymer of the vinyl acetate with vinyl alcohol esters of fatty acids. 3. Preparation as claimed in claim 1, whereby the content of polymethyl vinyl ether-maleic acid anhydride copolymer is 5 to 35%-wt. 4. Preparation as claimed in claim 1 or 2, whereby the content of polyvinyl acetate or of the copolymer or copolymers of the vinyl acetate with vinyl alcohol esters of fatty acids amounts to 4 to 35%-wt. 5. Preparation as claimed in anyone of the preceding claims, whereby the active substance is poorly soluble in water or is sensitive to water. 6. Preparation as claimed in any one of the preceding claims, whereby it has an additional content of carboxymethyl cellulose or at least one of its salts. 7. Preparation as claimed in claim 6, whereby the content of carboxymethyl cellulose or its salts is 5 to 35%-wt. 8. Preparation as claimed in anyone of the preceding claims, whereby the preparation has a layer thickness of 4 to 2000 µm, preferably 40 to 500 µm, and particularly preferably 60 to 250 µm. 9. Process for the manufacture of a preparation as claimed in claim 1, characterised by - mixing of, at least, a) - 4 to 35 %-wt. of polyvinyl acetate, relative to the solids content, - 5 to 35%-wt. of a polymethyl vinyl ether-maleic acid anhydride copolymer, relative to the solids content, as well as b) at least one cosmetic or pharmaceutical active substance in a solvent that contains one or more organic solvents as its main component selected from the group comprising methyl ethyl ketone, ethyl acetate, ethanol, acetone and mixtures thereof, whereby the organic solvent contains 1 to 5%-wt. of water, - coating a substrate with the mixture thus obtained, and - removing the solvent by drying. 10. Process as claimed in claim 9, whereby the mixture additionally contains a copolymer of the vinyl acetate with vinyl acetate esters of fatty acids. 11. Process as claimed in claim 10, whereby the content of the copolymer(s) of the vinyl acetate with vinyl alcohol esters of fatty acids is 4 to 35 %-wt., relative to the solids content. 12. Process as claimed in claim 9, whereby the active substance is poorly soluble in water or is sensitive to water. 13. Process as claimed in claim 9, whereby the organic solvent is a mixture of ethanol and methyl ethyl ketone. 14. Process as claimed in claim 13, whereby the mixture has a content of ethanol of 5 to 20%-wt. 15. Process as claimed in anyone of claims 9 to 14, whereby carboxymethyl cellulose or at least one of the salts thereof is added to the compound before it is spread onto the support. 16. Process as claimed in claim 15, whereby the content of carboxymethyl cellulose or the salts thereof is 5 to 35%-wt, relative to the solids content. 17. Process as claimed in any one of claims 9 to 16, whereby after drying of the coating, one or more further layers are applied to the already present layer(s) by hot lamination or by coating the existent layer(s) with one or more solvent-containing compounds. 18. Process as claimed in any one of claims 9 to 17, characterised by application of the compound onto the support, so that, after drying, a layer thickness of 4 to 2000 µm, preferably 40 to 500 µm, and particularly preferably 60 to 250 µm, is obtained. 19. A preparation as claimed in any of claims 1 to 8, wherever used for cosmetic or pharmaceutical treatment of the oral region, especially the teeth or gums.

Full Text

Self-adhesive film for teeth
The present invention relates to film-shaped preparations
which are pressure-sensitive adhesive to teeth, gums or the
oral mucosa and which are suitable for cosmetic or medical
treatment of the teeth, especially the tooth necks, and of
the gums. In addition, the present invention relates to a
process for the manufacture of such film-shaped preparations
Products for cleaning one's mouth and for active substance
delivery having the form of pastes, creams or mouth rinses
have long since been known and have been available on the
market. These products include tooth pastes and creams
which have a cleaning effect, protect against caries, are
desensitizing, or have a bleaching effect. Also known are
creams, gels and ointments that are applied in the oral region
for treating local illnesses and disorders such as
anti-inflammatory remedies, analgesic remedies and/or tonics
For some years, film-shaped, flat-shaped or strip-shaped
oral application forms, too, have been commercially available
and are used for cosmetic or therapeutic purposes.
These application forms include, for example, the Listerine
Pocket-Paks® by Pfizer or the "Teeth Whitestrips" by Procter
& Gamble. Such application forms are as a rule based on
films made up of water-soluble polymers which on use disintegrate
rather quickly and are therefore not suitable for a
longer-lasting treatment.
In addition, products are known that consist of several
layers, such as those disclosed in US 6,582,708, which,
In addition, products are known that consist of several
layers, such as those disclosed in US 6,582,708, which,
however, include only one flexible layer and which, due to
their overall thickness of up to 3 mm, are disturbing and
unpleasant in the mouth.
The recipes and methods used in the manufacture of the
known film-shaped application forms, for the most part,
start from water or from water-containing alcoholic polymer
solutions. A disadvantage here is that there are limitations
to preparing a completely dissolved formulation of
lipophile, poorly water-soluble active substances or of active
substances that are sensitive to water.
The object of the present invention was thus to provide a
mono- or multilayered, water-soluble or at least partially
water-swellable, film-shaped material which has good adhesion
to teeth, gums or the oral mucosa, which is suitable
as active substance carrier, and which does not already
disintegrate within a few seconds. More particularly, the
object is to provide a film-shaped material of the aforementioned
type which enables administration of waterinsoluble
or water-sensitive active substances.
This object is achieved by providing a mono- or multilayered,
pressure-sensitive-adhesive, film-shaped preparation
which contains at least one polymethyl vinyl ether-maleic
acid anhydride copolymer, polyvinyl acetate and/or at least
one copolymer of the vinyl acetate with vinyl alcohol esters
of fatty acids, as well as at least one cosmetic
and/or pharmaceutically active substance.
Preferably, the content of polymethyl vinyl ether-maleic
acid anhydride copolymer in the film-shaped, pressure sensitive
adhesive preparations is 5 to 35%-wt.
The content of polyvinyl acetate and/or of the copolymer(s)
of the vinyl acetate with vinyl alcohol esters of fatty acids
in the film-shaped, pressure-sensitive-adhesive preparations
preferably amounts to 4 to 35%-wt.
The film-shaped, pressure-sensitive adhesive preparations
in addition have a content of at least one cosmetic and/or
pharmaceutical active substance which is determined by the
nature of the illness or by the cosmetic needs. The active
substance is preferably a poorly water-soluble active substance
or a water-sensitive active substance.
The term "poorly water-soluble active substances" is understood
to mean such active substances as have a solubility
in water of less than 1 g/1. These include, for example,
griseofulvin, estradiol and vitamin D3.
The water-sensitive active substances include those active
substances, the aqueous solution of which looses more than
0.1% of its active substance content within 24 hours at
room temperature due to decomposition of the active substance.
The water-sensitive active substances include, for
example, acetylsalicylic acid and iodine.
In a particularly preferred embodiment, the film-shaped,
pressure-sensitive adhesive preparation in addition contains
carboxrymethyl cellulose and/or one of its salts. The
content of carboxymethyl cellulose or of one of its salts
in the preparation amounts to 5 to 35%-wt.
To manufacture the film-shaped preparations, which are
pressure-sensitive adhesive on teeth, gums or the oral mucosa,
the various, water-soluble and/or water-swellable
polymers are mixed with at least one active substance in
solutions containing organic solvents as main component.
This mixture is used to coat a substrate, and the coated
substrate is dried, optionally by application of heat.
The advantages of the invention arise especially where mixtures
of polymethyl vinyl ether-maleic acid anhydride copolymers
with polyvinyl acetate or the copolymers of the
vinyl acetate with vinyl alcohol esters of fatty acids, are
used.
The content of polymethyl vinyl ether-maleic acid anhydride
copolymer is preferably 5 to 35%-wt., and the content of
polyvinyl acetate and/or the copolymer(s) of the vinyl acetate
with vinyl alcohol esters of fatty acids is preferably
4 to 35%-wt., in each case relative to the solids content.
The polymethyl vinyl ether-maleic acid anhydride copolymers
sold under the name of "Gantrez®" by the firm of ISP, and
the polyvinyl acetates or copolymers of the vinyl acetate
with vinyl alcohol esters of fatty acids, designated as
"VINNAPAS®", of the firm of Wacker Polymer Systems,
Burghausen, have proved to be particularly suitable in accordance
with the present invention.
Any solvents which dissolve the polymethyl vinyl ethermaleic
acid anhydride copolymers and polyvinyl acetate or
copolymers of the vinyl acetate with vinyl alcohol esters
of fatty acids may be used as the organic solvents which,
in the method according to the invention, are contained in
the solution as the main component thereof. Of these organic
solvents, those are used with preference which also
mix with water since by adding small amounts of water, e.g.
of 1 to 5%-wt., the dissolving power for the polymers and
the active substance/active substances can be adapted to
the given requirements. Particular preference is given to
those organic solvents which permit addition of the active
substance dissolved in ethanol or in an ethanol-water mixture.
The especially preferred organic solvent is selected
from the group comprising methyl ethyl ketone, ethyl acetate,
ethanol, acetone and mixtures thereof.
The consistency and/or tackiness of the resultant filmshaped
preparations can be adapted to the demands placed on
the product by altering the mixing ratio of ethanol and
methyl ethyl ketone. Solvent mixtures containing an ethanol
portion of 5 to 20%-wt., relative to the total solvent,
have proved advantageous.
To manufacture a preferred embodiment enabling a particularly
successful adhesion of the film-shaped preparations
Multilayer/ pressure-sensitive-adhesive film-shaped preparations,
with which it is possible to achieve, for example,
an, improved adhesion of the preparation to teeth, can be
prepared, for example, by hot lamination, by coating already
existent layers with further solvent-containing compounds,
as described hereinabove in connection with the
manufacture of a monolayer film, or by other processes
known to those skilled in the art.
Pieces having a size appropriate to the respective given
purposes are then punched out from the film or laminate.
The process according to the present invention results in
film-shaped preparations which adhere to teeth, gums or the
oral mucosa, which do not already disintegrate within a few
seconds, and by means of which water-insoluble and even water-
sensitive active substances can be administered. These
preparations may advantageously be utilised for medical or
cosmetic treatments.
Example:
5g of a 33.3% solution (%-wt.) of a vinyl acetate-based
polymer in methyl ethyl ketone and 3 g of a 15% solution
(%-wt.) of polymethyl vinyl ether-maleic acid anhydride (=
copolymer of methyl vinyl ether and maleic acid anhydride)
in ethyl acetate were added together and homogenised. This
resulted in a solution which was spread at various coating
thicknesses and, subsequently, dried. This yielded flexible
films which adhered both to the oral mucosa and to the
teeth.

We Claim:
1. Mono- or multilayer, film-shaped, pressure-sensitive-adhesive preparation for application in
the oral region, and containing at least a layer containing
- a polymethyl vinyl ether-maleic acid anhydride co-polymer; polyvinyl acetate; and
- at least one cosmetic or pharmaceutical active substance.

2. Preparation as claimed in claim 1, whereby the layer additionally contains a copolymer of the vinyl acetate with vinyl alcohol esters of fatty acids.
3. Preparation as claimed in claim 1, whereby the content of polymethyl vinyl ether-maleic acid anhydride copolymer is 5 to 35%-wt.
4. Preparation as claimed in claim 1 or 2, whereby the content of polyvinyl acetate or of the copolymer or copolymers of the vinyl acetate with vinyl alcohol esters of fatty acids amounts to 4 to 35%-wt.
5. Preparation as claimed in anyone of the preceding claims, whereby the active substance is poorly soluble in water or is sensitive to water.
6. Preparation as claimed in any one of the preceding claims, whereby it has an additional content of carboxymethyl cellulose or at least one of its salts.
7. Preparation as claimed in claim 6, whereby the content of carboxymethyl cellulose or its salts is 5 to 35%-wt.
8. Preparation as claimed in anyone of the preceding claims, whereby the preparation has a layer thickness of 4 to 2000 µm, preferably 40 to 500 µm, and particularly preferably 60 to 250 µm.
9. Process for the manufacture of a preparation as claimed in claim 1, characterised by
- mixing of, at least,
a) - 4 to 35 %-wt. of polyvinyl acetate, relative to the solids content, - 5 to 35%-wt. of a polymethyl vinyl ether-maleic acid anhydride copolymer, relative to the solids content, as well as b) at least one cosmetic or pharmaceutical active substance in a solvent that contains one or more organic solvents as its main component selected from the group comprising methyl ethyl ketone, ethyl acetate, ethanol, acetone and mixtures thereof, whereby the organic solvent contains 1 to 5%-wt. of water,
- coating a substrate with the mixture thus obtained, and
- removing the solvent by drying.

10. Process as claimed in claim 9, whereby the mixture additionally contains a copolymer of the vinyl acetate with vinyl acetate esters of fatty acids.
11. Process as claimed in claim 10, whereby the content of the copolymer(s) of the vinyl acetate with vinyl alcohol esters of fatty acids is 4 to 35 %-wt., relative to the solids content.
12. Process as claimed in claim 9, whereby the active substance is poorly soluble in water or is sensitive to water.
13. Process as claimed in claim 9, whereby the organic solvent is a mixture of ethanol and methyl ethyl ketone.
14. Process as claimed in claim 13, whereby the mixture has a content of ethanol of 5 to 20%-wt.
15. Process as claimed in anyone of claims 9 to 14, whereby carboxymethyl cellulose or at least one of the salts thereof is added to the compound before it is spread onto the support.
16. Process as claimed in claim 15, whereby the content of carboxymethyl cellulose or the salts thereof is 5 to 35%-wt, relative to the solids content.
17. Process as claimed in any one of claims 9 to 16, whereby after drying of the coating, one or more further layers are applied to the already present layer(s) by hot lamination or by coating the existent layer(s) with one or more solvent-containing compounds.
18. Process as claimed in any one of claims 9 to 17, characterised by application of the compound onto the support, so that, after drying, a layer thickness of 4 to 2000 µm, preferably 40 to 500 µm, and particularly preferably 60 to 250 µm, is obtained.
19. A preparation as claimed in any of claims 1 to 8, wherever used for cosmetic or pharmaceutical treatment of the oral region, especially the teeth or gums.

Documents:

2661-DELNP-2007-Abstract-(02-09-2011).pdf

2661-delnp-2007-abstract.pdf

2661-DELNP-2007-Claims-(02-09-2011).pdf

2661-delnp-2007-claims.pdf

2661-delnp-2007-correspondece-others.pdf

2661-DELNP-2007-Correspondence Others-(02-09-2011).pdf

2661-DELNP-2007-Correspondence Others-(30-05-2011).pdf

2661-delnp-2007-correspondence-others 1.pdf

2661-delnp-2007-description (complete).pdf

2661-DELNP-2007-Form-1-(02-09-2011).pdf

2661-delnp-2007-form-1.pdf

2661-delnp-2007-form-18.pdf

2661-DELNP-2007-Form-2-(02-09-2011).pdf

2661-delnp-2007-form-2.pdf

2661-DELNP-2007-Form-3-(02-09-2011).pdf

2661-DELNP-2007-Form-3-(30-05-2011).pdf

2661-delnp-2007-form-3.pdf

2661-DELNP-2007-Form-5-(02-09-2011).pdf

2661-delnp-2007-form-5.pdf

2661-DELNP-2007-GPA-(02-09-2011).pdf

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Patent Number

251449

Indian Patent Application Number

2661/DELNP/2007

PG Journal Number

12/2012

Publication Date

23-Mar-2012

Grant Date

16-Mar-2012

Date of Filing

10-Apr-2007

Name of Patentee

LTS LOHMANN THERAPIE-SYSTEME AG

Applicant Address

LOHMANNSTRASSE 2, 56626 ANDERNACH, GERMANY

Inventors:

#	Inventor's Name	Inventor's Address
1	BOTZEM, PETRA	ST.THOMASER HOHL 24, 56626 ANDERNACH, GERMANY
2	LAUX, WOLFGANG	AM KATZENSTEIN 2B, 65582 DIEZ, GERMANY

PCT International Classification Number

A61K 8/02

PCT International Application Number

PCT/EP2005/010749

PCT International Filing date

2005-10-06

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	10 2004 049 740.0	2004-10-13	Germany