U.S. patent application number 10/444512 was filed with the patent office on 2004-04-01 for erodible film for treating the surfaces of teeth.
Invention is credited to Callahan, Ernest Howard JR., Moro, Daniel G., Nowotnik, David P..
Application Number | 20040062724 10/444512 |
Document ID | / |
Family ID | 25460591 |
Filed Date | 2004-04-01 |
United States Patent
Application |
20040062724 |
Kind Code |
A1 |
Moro, Daniel G. ; et
al. |
April 1, 2004 |
Erodible film for treating the surfaces of teeth
Abstract
A thin, flexible, bilayer or multi-layer film which when applied
to teeth surfaces adheres and delivers an active compound to the
underlying surface and erodes at a predetermined rate. The amount
of time that the active agent remains in contact with the teeth
surfaces is controlled by the composition of backing layer of the
composite film. This erosion or residence time can be regulated one
half hour to three hours, depending upon the desired therapeutic or
cosmetic application.
Inventors: |
Moro, Daniel G.; (Dallas,
TX) ; Callahan, Ernest Howard JR.; (North Richland
Hills, TX) ; Nowotnik, David P.; (Colleyville,
TX) |
Correspondence
Address: |
BINGHAM, MCCUTCHEN LLP
THREE EMBARCADERO, SUITE 1800
SAN FRANCISCO
CA
94111-4067
US
|
Family ID: |
25460591 |
Appl. No.: |
10/444512 |
Filed: |
May 23, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10444512 |
May 23, 2003 |
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09931319 |
Aug 16, 2001 |
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6585997 |
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Current U.S.
Class: |
424/53 |
Current CPC
Class: |
A61P 5/00 20180101; A61P
9/10 20180101; A61P 43/00 20180101; A61K 9/006 20130101; A61P 31/12
20180101; A61P 25/04 20180101; A61P 17/12 20180101; A61P 23/02
20180101; A61P 31/04 20180101; A61P 9/00 20180101; A61P 7/04
20180101; A61P 37/08 20180101; A61P 29/00 20180101; A61P 17/02
20180101 |
Class at
Publication: |
424/053 |
International
Class: |
A61K 007/20 |
Claims
1. An erodible strip comprising at least two layers, wherein one
layer comprises a water soluble polymer or combination of polymers
that adheres to moist enamel surfaces; and a second layer which is
water erodible and controls the residence time that the strip
remains adhered to the enamel surface.
2. The erodible strip of claim 1 being geometrically shaped as a
strip to conform to an individual tooth or a row of teeth.
3. The strip of claim 2 wherein said water soluble polymer is at
least one of polyvinyl pyrrolidone, polyvinyl alcohol, hydroxyethyl
cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose,
sodium carboxymethyl cellulose, polyethylene oxide, polyethylene
glycol, and polyacrylic acid.
4. The strip of claim 2 wherein said first layer comprises a water
soluble polymer or combination of polymers thereof and at least one
tooth-whitening agent.
5. The strip of claim 4 wherein said tooth whitening agent is at
least one selected from the group consisting of peroxides, metal
chlorites, perborates, percarbonates, peroxyacids, and
persulfates.
6. The strip of claim 4 wherein said tooth whitening agent is
carbamide peroxide.
7. The strip of claim 2 wherein said second layer comprises a
mixture of hydrophobic and water soluble polymers, consisting of
either ethyl cellulose, methyl cellulose, or anionic, cationic and
neutral polymers and copolymers of methacrylates under the trade
name Eudragit.RTM., alone or in combination thereof with at least
one water soluble polymer selected from the group consisting of
polyvinyl pyrrolidone, hydroxypropylmethyl cellulose, hydroxyethyl
cellulose, and polyvinyl alcohol.
8. The strip of claim 7 wherein said second layer comprises a
mixture of hydrophobic and water soluble polymers at a ratio of
0.5:1 to 10:1 by weight.
9. The strip of claim 8 where the ratio is 1.5:1 to 3:1 by
weight.
10. A strip film of claim 1 comprising a first layer consisting of
a water soluble polymer or combination of polymers that adheres to
moist enamel surfaces, a laminated middle layer comprising a
precast film of a water soluble polymer, and a water erodible
backing layer that controls the residence time that the film
remains adhered to a tooth surface.
11. The strip of claim 10 defined as is geometrically shaped to
conform to an individual tooth or a row of teeth.
12. The strip of claim 10 wherein the precast water soluble polymer
is hydroxypropylmethyl cellulose.
13. The strip of claim 10 wherein said first layer comprises at
least one water soluble polymer and at least one tooth whitening
agent.
14. The strip of claim 10 wherein a laminating solution used to
effectively bind the middle layer to the other two layers is
composed of at least one water soluble polymer dissolved in
alcohol, water, or an aqueous alcohol mixture.
15. The strip of claims 4 or 13 wherein said whitening agent is
from 0.1% to 30% by weight of the strip.
16. The strip of claims 4 or 13 where said whitening agent is from
0.5% to 20% by weight.
17. The erodible teeth whitening strip of claims 2 or 11 defined
further as containing propylene glycol, polyethylene glycol,
glycerin, sorbitol, or glycerol acetate plasticizer at a
concentration of 0.2% to 30% by weight.
18. The strip of claim 17 where the concentration is 0.5 to 10% by
weight.
19. The erodible teeth whitening strip of claims 2 or 11 defined
further as containing a titanium dioxide, zinc oxide or zirconium
silicate colorant or opacifier as an appearance enhancer.
20. The strip of claim 19 where the appearance enhancer is at a
concentration of 0.01% to 10% by weight.
21. The strip of claim 19 where the appearance enhancer is 0.03% to
1% by weight.
22. The erodible, teeth whitening strip of claims 2 and 11 defined
further as containing at least one of a preservative, antioxidant,
or flavor.
23. The strip of claim 19 where the appearance enhancer is at a
concentration of 0.01% to 2% by weight.
24. The strip of claim 3 wherein said polymer is in a molecular
weight range of between 25,000 and 1,500,000 Daltons.
25. The strip of claim 3 where said polymer is in a molecular
weight range of 30,000 and 500,000 Daltons.
26. The strip of claims 2 or 11 wherein said first layer comprises
at least one water soluble polymer and at least one compound that
dissociates to release fluoride ions for the prevention of
caries.
27. The strip of claims 2 or 11 wherein said first layer comprises
at least one water soluble polymer and at least one phosphate
compound for tartar control.
28. The strip of claims 2 or 11 wherein said first layer comprises
at least one water soluble polymer and at least one ingredient that
can cosmetically alters the appearance of teeth.
29. A mucoadhesive, erodible multi-layered device comprising a
first, water-soluble adhesive layer to be placed in contact with a
mucosal surface and a second, water-erodible non-adhesive backing
layer that controls residence time of the device; wherein said
first layer comprises a tooth-whitening agent, at least one
water-soluble film-forming polymer in combination with at least one
mucoadhesive polymer; and said second, water-erodible non-adhesive
backing layer comprises a precast film containing at least one of
hydroxypropyl methylcellulose, hydroxyethyl cellulose,
hydroxypropyl cellulose, polyvinyl alcohol, polyethylene glycol,
polyethylene oxide, and ethylene oxide-propylene oxide co-polymer,
said backing layer being coated with at least one hydrophobic
polymer, alone or in combination with at least one hydrophilic
polymer, such that the backing layer is bioerodible.
30. The mucoadhesive, erodible multi-layered device of claim 29,
wherein said second water-erodible non-adhesive backing layer acts
as a casting and support surface on which the adhesive layer is
prepared, and comprises a premade film of hydroxypropyl methyl
cellulose in combination with a coating consisting of at least one
hydrophobic polymer selected from the family of quaternary ammonium
acrylate/methacrylate co-polymers, (Eudragit RS) ethyl cellulose
and methyl cellulose, alone or in combination with at least one
hydrophilic polymer, selected from the group consisting of
polyvinyl pyrrolidone, hydroxypropyl methylcellulose, hydroxyethyl
cellulose, hydroxypropyl cellulose, and polyvinyl alcohol.
31. The device of claim 29 where the tooth-whitening agent is
carbamide peroxide.
Description
[0001] This application is a continuation-in-part and is based on
and claims priority from U.S. patent application Ser. No.
09/931,319, filed Aug. 16, 2001 and is incorporated herein by
reference.
FIELD OF THE INVENTION
[0002] This invention relates to the cosmetic or therapeutic
treatment of teeth, and more specifically to an adherent, erodible
film that provides an active ingredient agent to teeth surfaces for
a prolonged and controlled period of time.
BACKGROUND OF THE INVENTION
[0003] A tooth is composed of a protective, hard enamel outer layer
and an inner dentin layer. The enamel layer is typically opaque
white or slightly off-white in color. This layer is composed of
hydroxyapatite mineral crystals and is somewhat porous, allowing
staining agents and discoloring substances to permeate the enamel
and discolor teeth. In particular, certain foods, tobacco products
and liquids such as tea and coffee tend to stain teeth. These
substances accumulate on the surface and form a film on the teeth,
and will then permeate into the enamel layer. This problem occurs
over many years, imparting a noticeable discoloration of the enamel
layer.
[0004] There have been numerous methods in the prior art relating
to teeth whitening, including brushing the teeth using dentifrices
containing an effective oxidizing agent such as peroxide. These
types of compositions are disclosed in U.S. Pat. No. 5,256,402.
More recently, several over-the-counter teeth whitening systems
have become available and have gained in popularity as an
alternative cosmetic treatment to teeth whitening procedures
conducted by a professional. One such product is comprised of a
thin strip of plastic film that has a tooth whitening composition
applied to the surface as described in U.S. Pat. Nos. 5,894,017,
5,891,453 and 6,045,811. In addition, U.S. Pat No. 6,419,906 B1
describes a flexible film which when applied to stained teeth is
hydrated by saliva and is effective in such form to whiten teeth.
The film comprises an anhydrous water hydratable ethylene oxide
polymer matrix containing a solid peroxide whitening agent whereby,
upon placing and positioning on stained teeth, the peroxide is
solubilized and activated by the saliva present in the oral cavity.
These aforementioned systems produce a whitening effect when
applied to stained teeth; however, the strips must be removed after
a specified period of time. U.S. patent application Ser. No.
09/931,319 teaches the administration of pharmaceutically active
compounds using a multi-layered mucoadhesive erodible drug delivery
device. Although this reference relates to an oral pharmaceutical
application unrelated to teeth whitening, one important teaching is
that the length of time the device remains on the mucosal surface
before complete erosion, the "residence time", is easily modified
by alterations of the backing layer. It is this teaching that will
be utilized and adapted to the present invention relating to an
erodible tooth-whitening strip. In the area of cosmetic dentistry,
there is an ongoing need to improve the whitening efficiency and to
provide more user-friendly over-the-counter products.
SUMMARY OF THE INVENTION
[0005] One object of the present invention is to provide a novel,
cost-effective, erodible, layered device that adheres to the moist
surfaces of teeth and delivers an active agent for a controlled
period of time. Another object of the present invention is to
provide a convenient, user-friendly, erodible, layered device that
adheres to the moist teeth surfaces and delivers a tooth whitening
agent to the underlying stained surfaces. A further object of this
invention is to provide a tooth whitening device that is easily
applied without breaking or leaving any unwanted residue on the
hands. A further object of the present invention is to provide a
flexible, layered device that conforms and adheres intimately and
securely to the entire tooth surface, minimizing the exposure of
any excess whitening agent to the surrounding gums as found with
other competitive products.
[0006] The composition of the bi-layered and multi-layered devices
consists of an enamel adherent, water soluble, polymeric layer
containing a tooth whitening agent or other active compound and a
coated, erodible backing layer that controls the desired residence
time. Since the devices of the current invention can provide a
longer contact time with a stained tooth surface before eroding, it
is expected that lower and safer amounts of whitening agents can be
used to accomplish similar or superior results than attained by
other commercial products.
[0007] An important aspect of the present invention is an erodible
multilayered strip comprising at least two layers, a first layer
comprises a water soluble polymer or combination of polymers that
adheres to moist enamel surfaces. A second layer is water erodible
and controls the residence time that the strip remains adhere to
the enamel surface. This erodible strip is preferably shaped to
conform to an individual tooth or a row of teeth.
[0008] An important embodiment of the present invention involves
erodible adhesive a mucoadhesive, erodible multi-layered device
comprising a first, water-soluble adhesive layer to be placed in
contact with a mucosal surface and a second, water-erodible
non-adhesive backing layer that controls residence time of the
device. The first layer preferably comprises a tooth-whitening
agent, at least one water-soluble film-forming polymer in
combination with at least one mucoadhesive polymer; and said
second, water-erodible non-adhesive backing layer comprises a
precast film containing at least one of hydroxypropyl
methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose,
polyvinyl alcohol, polyethylene glycol, polyethylene oxide, and
ethylene oxide-propylene oxide co-polymer, said backing layer being
coated with at least one hydrophobic polymer, alone or in
combination with at least one hydrophilic polymer, such that the
backing layer is bioerodible.
[0009] An important aspect of the present invention is a
mucoadhesive, erodible multi-layered device comprising a first,
water-soluble adhesive layer to be placed in contact with a mucosal
surface and a second, water-erodible non-adhesive backing layer
that controls residence time of the device. The first layer
comprises a tooth-whitening agent (most preferably carbamide
peroxide), at least one water-soluble film-forming polymer in
combination with at least one mucoadhesive polymer. Said second,
water-erodible non-adhesive backing layer comprises a precast film
containing at least one of hydroxypropyl methylcellulose,
hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol,
polyethylene glycol, polyethylene oxide, and ethylene
oxide-propylene oxide co-polymer. This backing layer is coated with
at least one hydrophobic polymer, alone or in combination with at
least one hydrophilic polymer, such that the backing layer is
bioerodible. The second water-erodible non-adhesive backing layer
acts as a casting and support surface on which the adhesive layer
is prepared. It preferably, and comprises a premade film of
hydroxypropyl methyl cellulose in combination with a coating
consisting of at least one hydrophobic polymer selected from the
family of quaternary ammonium acrylate/methacrylate co-polymers,
(Eudragit RS) ethyl cellulose and methyl cellulose, alone or in
combination with at least one hydrophilic polymer, selected from
the group consisting of polyvinyl pyrrolidone, hydroxypropyl
methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose,
and polyvinyl alcohol.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0010] In the present invention, a unique, erodible, layered device
that adheres to tooth enamel surfaces is provided. The device is
most applicable for the cosmetic treatment of stained teeth, by
delivering a whitening agent or combination of agents thereof for a
controlled period of time. The device can also be used for the
delivery of fluoride ions and phosphates for the preventative
treatment of caries and tartar accumulation, respectively.
[0011] The device initially adheres to a moist tooth surface due to
the hydration and partial solubilization of the water soluble
polymer layer. The whitening agent that is dispersed throughout
this polymeric layer is then activated as it comes in contact with
saliva and is released to the underlying surface. The erosion rate
of the device is controlled by the coated backing layer, which
affects the amount of time the whitening agent remains in contact
with the enamel surface. The main purpose of the backing layer is
to slow down the dissolution of the water-soluble polymeric layer
containing a whitening agent, and therefore maximizing the direct
contact time and unidirectional delivery to the tooth surface. The
composition of the backing layer is easily adjusted to provide
variable erosion rates from one half hour to several hours. The
layered device is essentially totally erodible, and therefore does
not require removal after the appropriate treatment time.
[0012] The Residence Time as defined above is difficult to
quantitatively ascertain. One visual method is to apply the layered
device to the teeth surface and periodically observe the covered
surface using a mirror and assess approximately how much residue
remains on the surface. Typically, as the backing layer erodes away
at a predetermined rate, the adhesive swells and starts to dissolve
and fall off the teeth surface. The actual residence time on each
surface is controlled primarily by the flow of saliva to the
surface and any friction created by interaction with the internal
surface of the lips.
[0013] The polymeric coating layer that adheres to the tooth enamel
is composed of one or more adhesive polymers, an appropriate
whitening agent and a plasticizer. This coating may also contain an
antioxidant, a preservative and a taste-masking flavor.
[0014] The adhesive polymers can be any water soluble, FDA approved
polymer for oral applications that sticks to an enamel surface when
in contact with a moist tooth surface. The adhesive polymers may
comprise hydroxyethyl cellulose, hydroxypropyl cellulose,
hydroxypropylmethyl cellulose, hydroxyethylmethyl cellulose, sodium
carboxymethyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol,
polyethylene glycol, polyacrylic acid, polyethylene oxide, alone or
in combination thereof. The preferred adhesive polymers are
hydroxyethyl cellulose and polyvinyl pyrrolidone since they exhibit
rapid and effective adhesion to enamel when in contact with a moist
tooth surface.
[0015] The molecular weight of the adhesive polymer is also
important, since it must be large enough so that an integral film
can form, but not so large that immediate interfacial
solubilization and adhesion to the enamel surface is impaired.
Typical average molecular weights range between 50,000 and
1,500,000 Daltons, and preferably between 50,000 and 500,000.
[0016] The whitening agents suitable for the practice of the
present invention include peroxides, metal chlorites, perborates,
percarbonates, peroxyacids, persulfates, alone or in combination
thereof. Suitable peroxide compounds include hydrogen peroxide,
carbamide peroxide, calcium peroxide, and mixtures thereof. The
preferred peroxide is carbamide peroxide. Suitable metal chlorites
include calcium chlorite, barium chlorite, magnesium chlorite,
lithium chlorite, sodium chlorite, and potassium chlorite. The
preferred chlorite is sodium chlorite. A preferred percarbonate is
sodium percarbonate, and the preferred persulfates are oxones.
[0017] The rate at which the whitening agent is solubilized and
subsequently released to a tooth surface is controlled by varying
the film thickness, polymer properties such as structure and
molecular weight, type and properties of whitening agent and the
concentration of the whitening agent. The concentration of the
whitening agent typically varies from about 0.1% to about 30% by
weight of the total layered device, and preferably from about 0.5%
to about 20% by weight.
[0018] A plasticizer useful for purposes of the present invention
is selected from glycols such as propylene glycol, polyethylene
glycol, polyhydric alcohols such as glycerin and sorbitol and
glycerol esters such as glycerol triacetate. The plasticizer
comprises about 0.2% to about 30% by weight of the film of the
present invention and preferably about 0.5% to about 10% by
weight.
[0019] Glycerin and propylene glycol are the preferred plasticizers
for use in the present invention as well as polyethylene glycol.
The preferred molecular weights for polyethylene glycol are in the
range of 200-600 Daltons.
[0020] A colorant or opacifier can be incorporated in the adhesive
layer or any of the layers of this device for use as an appearance
enhancer. The colorant or opacifier comprises about 0.01% to about
10% by weight of the film of the present invention and preferably
about 0.03% to about 1% by weight. Colors and opacifiers may also
be used to help distinguish the non-adhesive backing layer from the
enamel adhering layer. Some opacifiers include titanium dioxide,
zinc oxide, zirconium silicate and others.
[0021] In addition to the incorporation of whitening agents, a
plasticizer, and colorants, there may also be included in the
adhesive film matrix a minor amount, e.g., 0.01 to 2% by weight, of
ingredients such as preservatives, antioxidants, and flavors.
[0022] The backing layer solution is composed of a mixture of a
hydrophobic polymer, such as ethyl cellulose, methyl cellulose,
propyl cellulose or other related polymers and copolymers, anionic,
cationic and neutral polymers and copolymers of methyl methacrylate
under the trade name EUDRAGIT.RTM., and a water soluble polymer
such as polyvinyl pyrrolidone, hydroxypropylmethyl cellulose,
hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol
or any other water soluble polymer that can be completely commixed
with the hydrophobic polymer(s), dissolved in ethanol or other
suitable organic solvent. The ratio of the hydrophobic to the
hydrophilic polymer is adjusted to increase or decrease the desired
residence time that the device remains on the teeth before complete
erosion. The ratio of hydrophobic to hydrophilic polymer ranges
from 0.5:1 to 10:1 by weight, and more preferably 1.5:1 to 3:1 by
weight.
[0023] The backing layer solution may also contain a plasticizing
agent, such as propylene glycol, polyethylene glycol, or glycerin,
in a small amount, 0.1 to 2.0% by weight, in order to improve the
flexibility and conformability of the resultant layered film and to
adjust the erosion rate of the device. Colors and opacifiers may
also be added to help distinguish the non-adhesive backing layer
from the enamel adhering layer.
[0024] Once dissolved, these solutions (adhesive and backing) are
cast and processed into a thin film by techniques known in the art,
such as by film dipping, film coating, film casting, spin coating,
or spray drying. These films are produced on an appropriate support
at the desired thickness and dried using an oven. The primary
support can be a polymer-coated paper, Mylar or any other
appropriate non-deformable and impervious surface. The preferable
primary support is coated paper. The primary support's casting
surface must hold the film dimensionally stable during the coating
and drying processes, but allow the resulting composite film to
release when desired. The actual casting surface for these
solutions may be the primary support or another layer of the device
being produced, such as the precast film layer or a freshly cast
adhesive or backing layer. The amount of coating solutions applied,
using a suitable doctor blade or lab coater apparatus, ranges
between 0.01 to 1.5 mm, and most preferably between 0.05 and 0.4 mm
for the backing layer and between 0.8 and 1.3 mm for the adhesive
layer. The amount of solids present in the coating solutions, the
resulting solution viscosity and coating thickness applied
determine the amount of coating film to be deposited on the casting
surface.
[0025] The final layered device will consist of an adhesive layer
and a hydrophobic layer with or without a precast
hydroxypropylmethyl cellulose (HPMC) film in-between. A precast
water soluble film between the adhesive and backing layers will
typically provide a longer residence time on the teeth. Several
methods of forming this device are now provided herein.
[0026] In one embodiment, the adhesive layer is formed on an
appropriate primary support. In a separate operation, the backing
layer is formed on a water soluble, polymeric precast film of HPMC.
The two films are then laminated, with the hydrophobic layer either
on the outside or in the middle of the final composite film, using
an appropriate binding solution such as polyvinylpyrrolidone
dissolved in a water/ethanol mixture. This multi-layered film can
be either peeled away from the primary support and cut into the
desired shape or cut with the primary support still attached.
[0027] In another embodiment, the backing layer is formed on an
appropriate primary support. A precast film of HPMC is then
laminated to the backing layer using binding solution consisting of
polyvinylpyrrolidone dissolved in a water/ethanol mixture. Then a
distinct binding layer, typically composed of polyvinylpyrrolidone
is formed on top of the HPMC precast film. Finally, the adhesive
layer is formed on top of the binding layer. This resulting
multi-layer film is then further processed as outlined above.
[0028] In a preferred embodiment, the adhesive layer is formed on
an appropriate primary support by the casting methods previously
described. The backing layer is then formed directly on top of the
adhesive layer. This two-layer film is then further processed as
outlined above.
[0029] In another preferred embodiment, the backing layer is formed
on an appropriate primary support by the casting methods previously
described The adhesive layer is then formed directly on top of the
backing layer and the resulting bilayered product is further
processed as outlined above.
[0030] The thicknesses of each layer will affect the residence time
of the device. The hydrophobic layer composition and thickness are
the most important parameters in controlling the residence time.
However, inclusion of the water soluble, polymeric precast film as
one of the layers of the device will also increase the residence
time, since the overall thickness of the device is increased.
[0031] The total thickness of the device is also an important
consideration in regards to user acceptance. A very thick device
becomes more noticeable with respect to "mouth feel", and may cause
the user to discontinue its use prematurely, thus compromising
efficacy.
[0032] The total thickness of the device will also affect its
ability to conform and adhere to teeth in an efficient manner.
Typically, thin films are preferred since they can be easily
applied and bent around the teeth, minimizing the amount of
unattached area in the form of edges and comers that could cause
the film to be accidentally pulled off the teeth. However, if the
film is too thin, it will begin to lose tensile strength and rip
during its application.
[0033] With respect to the individual layers of the composite film,
the thickness of the adhesive layer is between 50.mu. and 300.mu.,
and more preferably between 60.mu. and 140.mu.. The thickness of
the backing layer is between 50.mu. and 300.mu., and more
preferably between 60.mu. and 100.mu.. The thickness of the precast
layer if used to produce a multilayered device is between 25.mu.
and 200.mu., and more preferably between 50.mu. and 100.mu.. The
overall thickness of the device is between 75.mu. and 500.mu., and
more preferably between 125.mu. and 300.mu..
EXAMPLE 1
[0034] A 180.0 gram batch of placebo adhesive solution was prepared
using 10.0 grams hydroxyethyl cellulose (Natrosol 250L NF;
Hercules), 10.0 grams polyvinyl pyrrolidone (PVP; Povidone P-1416;
Spectrum), 0.65 grams sodium benzoate (Spectrum), 0.65 grams
propylene glycol (Spectrum), and 158.7 grams deionized and
0.22.mu.-filtered water. This solution was used in Example 11
below.
EXAMPLE 2
[0035] A 29.87 gram batch of active adhesive solution was prepared
using 4.37 grams hydroxyethyl cellulose (Natrosol 250L NF;
Hercules), 1.80 grams PVP (Povidone P-1416; Spectrum), 0.09 grams
sodium benzoate (Spectrum), 0.09 grams propylene glycol (Spectrum),
2.70 grams carbamide peroxide (Spectrum), and 20.82 grams deionized
and 0.22.mu.-filtered water. This solution was used in Examples 12
and 13 below.
EXAMPLE 3
[0036] A 25.94 gram batch of active adhesive solution was prepared
using 3.51 grams hydroxyethyl cellulose (Natrosol 250L NF;
Hercules), 1.66 grams PVP (Povidone P-1416; Spectrum), 0.08 grams
sodium benzoate (Spectrum), 0.08 grams propylene glycol (Spectrum),
2.49 grams carbamide peroxide (Spectrum), and 18.12 grams deionized
and 0.22.mu.-filtered water. This solution was used in Examples 14
and 15 below.
EXAMPLE 4
[0037] A 46.84 gram batch of active adhesive solution was prepared
using 2.70 grams hydroxyethyl cellulose (Natrosol 250L NF;
Hercules), 1.35 grams PVP (Povidone P-1416; Spectrum), 0.15 grams
sodium benzoate (Spectrum), 0.15 grams propylene glycol (Spectrum),
2.70 grams carbamide peroxide (Spectrum), 1.95 grams sodium
alginate, and 37.84 grams deionized and 0.22.mu.-filtered water.
This solution was used in Examples 16 and 17 below.
EXAMPLE 5
[0038] A 19.0 gm batch of backing solution was prepared using 2.0
grams of ethyl cellulose (Ethocel Premium Std 7; Dow Chemical), 1.0
grams of HPMC (Methocel E5 Prem LV; Dow Chemical), 1.0 gram Adams
Extract Red Food Color, and 15.0 grams ethanol (190 proof; USP;
Spectrum). This backing solution was used in Examples 11, 15, and
18 below.
EXAMPLE 6
[0039] A 16.5 gram batch of backing solution was prepared using 1.1
grams of ethyl cellulose, 1.1 grams of HPMC, 0.9 grams Adams
Extract Red Food Color, and 13.4 grams ethanol (190 proof, USP;
Spectrum). This backing solution was used to make Examples 16 and
17 below.
EXAMPLE 7
[0040] A 19.8 gram batch of backing solution was prepared using 2.2
grams of ethyl cellulose, 1.1 grams of HPMC, and 16.5 grams ethanol
(190 proof, USP; Spectrum). This backing solution was used to make
Examples 12, 13, 19, and 20 below.
EXAMPLE 8
[0041] A 25.2 gram batch of backing solution was prepared using 1.8
grams of ethyl cellulose, 1.8 grams of HPMC, and 21.6 grams ethanol
(190 proof, USP; Spectrum). This backing solution was used to make
Examples 21 and 22 below.
EXAMPLE 9
[0042] A 52.7 gram batch of laminating solution was prepared using
6.32 grams PVP (P1416; Spectrum), 23.19 grams ethanol (190 proof,
USP; Spectrum), and 23.19 grams deionized and 0.22.mu.-filtered
water.
EXAMPLE 10
[0043] The precast HPMC film used in several embodiments of this
device was typically a 100.mu. thick sheet called EM1100 from
Polymer Films. In some embodiments, it was stretched on a
paper-and-foil frame of a Werner Mathis AG Lab Coater, type LTF,
and a backing solution selected from Examples 5-8 was poured on top
and doctor-bladed at a 0.25 mm setting, then dried in the oven
section of the Lab Coater.
EXAMPLE 11
[0044] A composite device was made by doctor-blading the adhesive
solution of Example 1 into a film using the Lab Coater. The casting
was performed on a polymer-coated paper from Fortifiber, which was
put on the paper and foil frame of the Lab Coater, with a doctor
blade setting of 1.76 mm. The film was automatically dried in the
oven portion of the Lab Coater, and a smooth, integral layer of
deposited, adhesive polymer resulted. Then, separately, a layer of
backing solution from Example 5 was doctor-bladed on top of the
precast HPMC film (Example 10) using a 0.25 mm setting. The two
films were then laminated together using the laminating solution
described in Example 9 and pressure from a roller, followed by
drying in the Lab Coater oven. The film was cut either before or
after removal from the coated paper and upon application to a moist
tooth surface, the film stuck well.
EXAMPLE 12
[0045] A composite device was made as in Example 11, except using
the adhesive of Example 2, with doctor-blade setting of 1.00 mm,
and the backing solution of Example 7. After cutting and removal
from the casting coated paper, the resulting film also stuck well
to teeth.
EXAMPLE 13
[0046] Another composite device was made by putting a backing layer
of 2:1 ethyl cellulose to HPMC as described in Example 7 on
polymer-coated paper (from Fortifiber) and then putting a layer of
whitening adhesive (Example 2) on top of it. The backing layer was
doctor-bladed at a 0.43 mm setting and the adhesive was
doctor-bladed at a setting of 1.30 mm. This film after removal from
the paper and cutting, stuck immediately and firmly to teeth,
conformed extremely well, and eroded away without notice.
EXAMPLE 14
[0047] A composite device composed of only an adhesive layer was
made using the process outlined in Example 11, except the adhesive
of Example 3 was used and with a doctor blade setting of 1.30 mm. A
test was done to determine the whitening efficacy of this adhesive
layer alone as compared to the competitive product Crest
Whitestrips. Both products were dampened and pressed onto a
coffee-stained white cup. They were removed after 16 hours. The
amount of whitening was compared and ranked by eight individuals
who did not know which device did which whitening. The results
shown below indicate that the adhesive layer containing a whitening
agent is as effective if not better than one competitive
product.
[0048] Adhesive only: 5 firsts, 1 tie, and 2 seconds; relative
average score=1.38
[0049] Crest White Strip: 2 first, 1 tie, and 5 seconds; relative
average score=1.75
EXAMPLE 15
[0050] A composite device was made by putting a layer of active
adhesive from Example 3 on a polymer-coated paper (Fortifiber) and
then putting a layer of backing solution from Example 5 on top of
it. The adhesive was doctor-bladed at settings of 1.30 mm. The
backing layer was spread thinly onto the surface of the dried
adhesive film using a spatula and then dried. This resulting film
after removal from the coated paper stuck well to the teeth.
EXAMPLE 16
[0051] A composite device was made as in Example 11, except using
the adhesive of Example 4 and with a doctor blade setting of 1.30
mm and the backing solution of Example 6 with a doctor blade
setting of 0.25 mm. A strip of this film after removal from the
surface of the coated paper and cutting, lasted about 11/2 hours on
the front teeth.
EXAMPLE 17
[0052] A composite device was made as in Example 15, except using
the adhesive of Example 4 and the backing solution of Example 6. A
strip of this film after removal from the surface of the coated
paper and cutting, lasted about 1 hour on the front teeth.
EXAMPLE 18
[0053] A composite device was made as in Example 11, except using
the adhesive of Example 3 without the tooth whitening agent,
carbamide peroxide, and doctor blade settings of 1.30 mm. After
processing, this placebo film visually seemed similar to the active
films and upon removal from the coated paper and cutting, stuck
comparably to the teeth.
EXAMPLE 19
[0054] A composite device was made as in Example 11, except using
the adhesive of Example 4, a doctor blade setting of 1.30 mm, and
the backing solution of Example 7.
EXAMPLE 20
[0055] A composite device was made as in Example 15, except using
the adhesive of Example 4, with a doctor blade setting of 1.30 mm,
and the backing solution of Example 7. The resulting film after
removal from the coated paper and cutting, lasted more than 1/2
hour on the front teeth.
EXAMPLE 21
[0056] A composite device was made as in Example 11, except using
the adhesive of Example 4, with doctor blade setting of 1.30 mm,
and the backing solution of Example 8. The resulting film after
removal from the coated paper and cutting, lasted about 11/2 hours
on the front teeth.
EXAMPLE 22
[0057] A composite device was made as in Example 15, except using
the adhesive of Example 4, with doctor blade setting of 1.30 mm,
and the backing solution of Example 8. The resulting film, after
removal from the coated paper and cutting, lasted about 1 hour on
the front teeth.
[0058] Those skilled in the art will recognize that, while specific
embodiments and examples have been described, various modifications
and changes may be made without departing from the scope and spirit
of this invention.
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