U.S. patent application number 11/836041 was filed with the patent office on 2008-09-25 for dental anti-hypersensitivity composition and method.
This patent application is currently assigned to Research Foundation of State of University of New York. Invention is credited to Ana Marie Acevedo, Robi Chatterjee, Israel Kleinberg.
Application Number | 20080233054 11/836041 |
Document ID | / |
Family ID | 22491802 |
Filed Date | 2008-09-25 |
United States Patent
Application |
20080233054 |
Kind Code |
A1 |
Kleinberg; Israel ; et
al. |
September 25, 2008 |
DENTAL ANTI-HYPERSENSITIVITY COMPOSITION AND METHOD
Abstract
The present invention relates to compositions and methods for
calcifying dental tissue, e.g., preventing or treating dental
hypersensitivity. An oral composition of arginine bicarbonate and
calcium carbonate promotes the formation of dentinal tubule plugs
aided by combining calcium and phosphate in the fluid. In a
specific example, an arginine bicarbonate/calcium carbonate mixture
blocked dentinal tubules in a model system. In addition to treating
dentinal sensitivity, the compositions and methods of the invention
provide for calcifying exposed tooth pulp, calcifying the base or
all of a pit or fissure in a tooth, and treating a carious
lesion.
Inventors: |
Kleinberg; Israel;
(Smithtown, NY) ; Acevedo; Ana Marie; (Caracas,
VE) ; Chatterjee; Robi; (Centereach, NY) |
Correspondence
Address: |
DARBY & DARBY P.C.
P.O. BOX 770, Church Street Station
New York
NY
10008-0770
US
|
Assignee: |
Research Foundation of State of
University of New York
Albany
NY
|
Family ID: |
22491802 |
Appl. No.: |
11/836041 |
Filed: |
August 8, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10328389 |
Dec 23, 2002 |
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11836041 |
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09940723 |
Aug 27, 2001 |
6524558 |
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10328389 |
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09504264 |
Feb 15, 2000 |
6436370 |
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09940723 |
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60140560 |
Jun 23, 1999 |
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Current U.S.
Class: |
424/48 ; 424/49;
424/57; 426/548; 426/648 |
Current CPC
Class: |
A61K 8/0241 20130101;
A61K 6/20 20200101; A61K 6/52 20200101; A61K 2800/59 20130101; A61Q
11/00 20130101; Y10S 514/835 20130101; A61K 8/19 20130101; A61K
8/42 20130101; A61K 8/44 20130101 |
Class at
Publication: |
424/48 ; 424/49;
424/57; 426/648; 426/548 |
International
Class: |
A61K 8/43 20060101
A61K008/43; A61K 8/55 20060101 A61K008/55; A61K 9/68 20060101
A61K009/68; A23L 1/30 20060101 A23L001/30; A23L 1/236 20060101
A23L001/236 |
Claims
1. A prophypaste comprising a guanidinium alkaline salt or free
base, a calcium salt which is poorly soluble in water, and an
orally acceptable carrier, wherein the pH of the prophypaste ranges
from about 7.5 to about 9.5.
2. The prophypaste of claim 1, wherein the guanidinium is
arginine.
3. The prophypaste of claim 2, wherein the arginine salt is
selected from the group consisting of arginine bicarbonate,
arginine hydroxide, arginine carbonate, arginine phosphate, and
arginine organic phosphate.
4. The prophypaste of claim 1, wherein the solubility of the
calcium salt is between about 0.1 and about 100 mg in 100 ml of
water near and about room temperature and near and above pH of
about 5.
5. The prophypaste of claim 1, wherein the calcium salt is selected
from the group consisting of calcium carbonate, monocalcium
phosphate, dicalcium phosphate, tricalcium phosphate, calcium
fluoride, calcium monofluorophosphate, sodium calcium
pyrophosphate, calcium laurate, calcium palmitate, and combinations
thereof.
6. The prophypaste of claim 1, further comprising a protein
denaturing agent.
7. A dental container comprising a packaging material and the
prophypaste of claim 1, wherein the prophypaste is effective in
retarding or preventing dentinal hypersensitivity.
8. The dental container of claim 7, wherein the dental container is
of a size that permits easy access of the rotary attachments used
in dental offices on dental hand-pieces.
9. A method of treating or preventing dentinal sensitivity in a
tooth, which method comprises applying the prophypaste of claim 1,
wherein a pH of the prophypaste ranges from about 7.5 to about 9.5,
to tooth surfaces exposed by gingival recession or tooth areas that
have a deficiency or have experienced loss of enamel or
cementum.
10. A method of plugging tubules, which method comprises
administering the prophypaste of claim 1, wherein a pH of the
prophypaste ranges from about 7.5 to about 9.5, to a tooth where
tubule plugging is desired.
11. A method of treating a carious lesion, which method comprises
administering the prophypaste of claim 1, wherein a pH of the
prophypaste ranges from about 7.5 to about 9.5, to the carious
lesion.
12. A method of calcifying an exposed tooth pulp, which method
comprises administering the prophypaste of claim 1, wherein a pH of
the prophypaste ranges from about 7.5 to about 9.5, to the exposed
tooth pulp.
13. A dental floss impregnated with a composition comprising a
guanidinium alkaline salt or free base, a calcium salt which is
poorly soluble in water, and an orally acceptable carrier, wherein
the pH of the composition ranges from about 7.5 to about 9.5.
14. The dental floss of claim 13, wherein the guanidinium is
arginine.
15. The dental floss of claim 14, wherein the arginine salt is
arginine bicarbonate, arginine hydroxide, arginine carbonate,
arginine phosphate, and arginine organic phosphate.
16. The dental floss of claim 13, wherein the calcium salt is
selected from the group consisting of calcium carbonate,
monocalcium phosphate, dicalcium phosphate, dicalcium phosphate,
tricalcium phosphate, calcium fluoride, calcium
monofluorophosphate, sodium calcium pyrophosphate, calcium laurate,
calcium palmitate, and combinations thereof.
17. A method of treating or preventing dentinal sensitivity in a
tooth, which method comprises applying the dental floss of claim 13
to tooth surfaces exposed by gingival recession or tooth areas that
have experienced loss of enamel or cementum.
18. A food product comprising a guanidinium alkaline salt or free
base, a calcium salt which is poorly soluble in water, and an
orally acceptable carrier, wherein the pH of the food product
ranges from about 7.5 to about 9.5.
19. The food product of claim 18, wherein the guanidinium is
arginine.
20. The food product of claim 19, wherein the arginine salt is
arginine bicarbonate, arginine hydroxide, arginine carbonate,
arginine phosphate, and arginine organic phosphate.
21. The food product of claim 18, wherein the calcium salt is
selected from the group consisting of calcium carbonate,
monocalcium phosphate, dicalcium phosphate, tricalcium phosphate,
calcium fluoride, calcium monofluorophosphate, sodium calcium
pyrophosphate, calcium laurate, calcium palmitate and combinations
thereof.
22. The food product of claim 18, further comprising a sweetening
agent.
23. The food product of claim 22, wherein the sweetening agent is
selected from the group consisting of saccharine, aspartame,
sorbitol, mannitol, and xylitol.
24. The food product of claim 18, wherein the guanidinium is
arginine bicarbonate and the calcium salt is calcium carbonate.
25. A method of treating or preventing dentinal sensitivity in a
tooth, which method comprises applying the food product of claim 18
to tooth surfaces exposed by gingival recession or tooth areas that
have a deficiency or have experienced loss of enamel or
cementum.
26. A method of calcifying the base or all of a pit or fissure in a
tooth, which method comprises administering the food product of
claim 18 into the pits and fissures.
27. A gum comprising a guanidinium alkaline salt or free base, a
calcium salt which is poorly soluble in water, and an orally
acceptable carrier, wherein the pH of the gum ranges from about 7.5
to about 9.5.
28. The gum of claim 27, wherein the guanidinium is arginine.
29. The gum of claim 28, wherein the arginine salt is arginine
bicarbonate, arginine hydroxide, arginine carbonate, arginine
phosphate, and arginine organic phosphate.
30. The gum of claim 27 wherein the calcium salt is selected from
the group consisting of calcium carbonate, monocalcium phosphate,
dicalcium phosphate, tricalcium phosphate, and combinations
thereof.
31. The gum of claim 27, wherein the guanidinium is arginine
bicarbonate and the calcium salt is selected from the group
consisting of calcium carbonate, calcium phosphate, and
combinations thereof.
32. A method of treating or preventing dentinal sensitivity in a
tooth, which method comprises administering the gum of claim 27 to
tooth surfaces exposed by gingival recession or tooth areas that
have a deficiency or have experienced loss of enamel or
cementum.
33. A method of calcifying the base or all of a pit or fissure in a
tooth, which method comprises administering the gum of claim 27
into the pits and fissures.
34. A confection comprising a guanidinium alkaline salt or free
base, a calcium salt which is poorly soluble in water, and an
orally acceptable carrier, wherein the pH of the composition ranges
from about 7.5 to about 9.5.
35. The confection of claim 34, wherein the guanidinium is
arginine.
36. The confection of claim 35, wherein the arginine salt is
arginine bicarbonate, arginine hydroxide, arginine carbonate,
arginine phosphate, and arginine organic phosphate.
37. The confection of claim 34, wherein the calcium salt is
selected from the group consisting of calcium carbonate,
monocalcium phosphate, dicalcium phosphate, tricalcium phosphate,
and combinations thereof.
38. The confection of claim 34, wherein the guanidinium is arginine
bicarbonate and the calcium salt is selected from the group
consisting of calcium carbonate, calcium phosphate, and
combinations thereof.
39. A method of treating or preventing dentinal sensitivity in a
tooth, which method comprises applying the confection of claim 34
to tooth surfaces exposed by gingival recession or tooth areas that
have a deficiency or have experienced loss of enamel or
cementum.
40. A method of calcifying the base or all of a pit or fissure in a
tooth, which method comprises administering the confection of claim
34 into the pits and fissures.
41. A dental care product impregnated with a composition comprising
a guanidinium alkaline salt or free base, a calcium salt which is
poorly soluble in water, and an orally acceptable carrier, wherein
the pH of the composition ranges from about 7.5 to about 9.5.
42. The dental care product of claim 41, wherein the guanidinium is
arginine.
43. The dental care product of claim 42, wherein the arginine salt
is arginine bicarbonate, arginine hydroxide, arginine carbonate,
arginine phosphate, and arginine organic phosphate.
44. The dental care product of claim 41, wherein the calcium salt
is selected from the group consisting of calcium carbonate,
monocalcium phosphate, dicalcium phosphate, tricalcium phosphate,
and combinations thereof.
45. A method of treating or preventing dentinal sensitivity in a
tooth, which method comprises applying the dental care product of
claim 41 to tooth surfaces exposed by gingival recession or tooth
areas that have a deficiency or have experienced loss of enamel or
cementum.
46. A method of calcifying the base or all of a pit or fissure in a
tooth, which method comprises administering the dental care product
of claim 41 into the pits and fissures.
Description
[0001] This application is a continuation of U.S. Ser. No.
10/328,389 filed Dec. 23, 2002; which is a continuation of U.S.
Ser. No. 09/940,723 filed Aug. 27, 2001; now issued U.S. Pat. No.
6,524,558; which is a continuation of U.S. Ser. No. 09/504,264
filed Feb. 15, 2000, now issued U.S. Pat. No. 6,436,370; which
claims priority to U.S. Provisional Application No. 60/140,560
filed Jun. 23, 1999, all incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to compositions and methods
for preventing or treating dental hypersensitivity.
BACKGROUND OF THE INVENTION
[0003] The three mineralized tissues of teeth are enamel, cementum
and dentine. In human teeth, enamel covers the crown dentine
whereas cementum covers the root dentine. In turn, the dentine
encloses the pulp of the tooth which provides the dentine with
vascular and neural support. Unlike enamel and cementum, the
dentine is transversed by numerous tubules. The tubule walls are
comprised of the calcified matrix of the dentine and the tubule
space is filled with fluid (dentinal fluid) derived from pulp
tissue fluid and serum. The matrix mineral is comprised mainly of
the calcium phosphate salt, hydroxyapatite, which is poorly soluble
at neutral and alkaline pH, and progressively more soluble as the
pH becomes progressively more acidic.
[0004] Because of their rigid walls, the fluid that fills the
narrow dentinal tubules enables cold, tactile, evaporative and
osmotic stimuli to be transmitted through the dentine to the pulp
in the form of fluid movement. This movement of dentinal fluid is
sensed as sharp pain of short duration. This pain is elicited when
the odontoblasts that protrude into the pulpal ends of the tubules
are disturbed and as a result, the mechano-receptors of the pulpal
nerve fibers attached thereto are stimulated. The neural response
is usually referred to as dentinal pain and the involved dentine as
hypersensitive dentine.
[0005] Dentinal hypersensitivity results when protective enamel or
cementum covering dentine is lost. Cementum is easier to breach
than enamel, because cementum is thinner and more easily eroded by
acids. However, breach of cementum cannot happen until there is
gingival recession and exposure of the root surface to the oral
milieu. Individuals with breached cementum and suffering with
dentinal hypersensitivity often experience pain when the exposed
area of the tooth comes into contact with cold air or hot and cold
liquids or foods that are sweet or acidic or is touched with a
metal object.
[0006] One way that loss of cementum occurs (and the same is true
of enamel) is by the process of dental caries. Acids are produced
as end-products of the bacterial degradation of fermentable
carbohydrate and these acids dissolve hydroxyapatite, which, like
dentine and enamel, is the main calcium phosphate mineral that
comprises most of the mineral of the cementum. Another source is
acidic foods which, if ingested frequently and for prolonged
periods of time, will cause tooth demineralization. These include
fruit juices and many beverages, both alcoholic and non-alcoholic.
Other acidic agents leading to chemical erosion include various
oral personal care products. Amongst these are many of the
commercially available mouthwashes and some toothpastes. Abrasive
toothpastes and vigorous brushing can aid the erosion process.
Another way in which dentinal tubules lose their protective
cementum and enamel coverings is through procedures performed by
the dentist or hygienist in the dental office. This includes cavity
and crown preparation of teeth for fillings and other restorations.
It also includes cementum removal during scaling and root planing
by the periodontist or dental hygienist.
[0007] Many attempts have been made with limited success to plug
exposed dentinal tubules and to thereby reduce or stop the ability
of stimuli to reach the pulp and cause pain. Materials either
singly or in combination have been tried to produce an effective
plug. Blockage of the tubules through the formation of a calcium
phosphate precipitate is a common approach. This includes the
mixing of a soluble calcium salt with a soluble phosphate salt and
immediately applying the combination to the open tubules.
Alternatively, application of one salt before the other to try to
get a precipitate to form within tubules is also used.
[0008] Substances other than calcium phosphate have also been
utilized. For example, U.S. Pat. No. 3,683,006 to Hodosh describes
using potassium, lithium or sodium nitrate. Another example is
calcium oxalate particles of small and large size. Application of a
protein denaturing agent, such as an alcohol, a surfactant, or a
chaotropic salt, can also plug an exposed dentinal tubule since
there is protein material within the dentinal tubules and
denaturation can sometimes result in partial or complete tubule
plugging. Still another but more drastic approach is to place a
dental restoration in the affected area or cover the area with an
adhesive material. For example, U.S. Pat. No. 5,139,768 to Friedman
describes using a varnish containing strontium salt in a sustained
hydrophobic polymer. Adherence without leakage of fluid from the
tubules is not always easy to accomplish because adherence to a wet
surface is difficult to achieve considering that the continual
outward flow or leakage of dentinal fluid from the tubules while a
filling or adhesive is setting is hard to stop.
[0009] Attempts to treat tooth sensitivity other than by plugging
have involved depolarization of the nerve fiber membranes essential
for nerve impulse transmission. Potassium salts, especially
potassium nitrate, have been largely used for this purpose. For
example, U.S. Pat. Nos. 4,751,072 and 4,631,185 to Kim describe
using potassium bicarbonate and potassium chloride.
[0010] Thus, there remains acute need in the art for compositions
and methods for blocking exposed dentinal tubules to treat dentinal
hypersensitivity.
[0011] There is a further need in the art to identify compositions
and methods that can achieve intrinsic blockage of dentinal
tubules, e.g., by taking advantage of the presence of calcium and
phosphate ions in dentinal fluid, which potentiates their ability
to precipitate as a calcium phosphate salt and achieve tubule
blockage.
[0012] The present invention advantageously provides such
compositions and methods.
SUMMARY OF THE INVENTION
[0013] The present invention advantageously provides an oral
composition comprising a guanidinium alkaline salt and a calcium
salt and an orally acceptable carrier, wherein the pH of the
composition ranges from about 7.5 to about 9.5, and the calcium
salt is poorly soluble in water. In a more specific embodiment, the
oral composition consists essentially of the guanidinium alkaline
salt and poorly soluble calcium salt with an orally acceptable
carrier. In yet a further embodiment, the oral composition
substantially lacks any phytates. Preferably, the guanidinium is
arginine and the calcium salt is calcium carbonate.
[0014] The invention further provides a powder composition
comprising, or more particularly consisting essentially of, an
arginine salt (or equivalent guanidinium salt) and calcium
carbonate (or an equivalent poorly soluble calcium salt). Such a
powder composition, when in contact with a calcium phosphate
solution or slurry, or a body fluid (e.g., dentinal fluid, saliva,
or pulpal fluid), body cells, or body tissues (e.g., dental pulp),
yields a pH ranging from about 7.5 to about 9.5. Preferably, the
powder composition lacks phytates.
[0015] In a further aspect, the invention provides a pulpal
calcification filling comprising, or more particularly consisting
essentially of, an arginine salt (or an equivalent guanidinium
salt) and calcium carbonate (or an equivalent poorly soluble
calcium salt) and a filling carrier, wherein the pH of the
composition ranges from about 7.5 to about 9.5.
[0016] The invention further provides methods for treating or
preventing dentinal sensitivity, plugging tubules, treating a
carious lesion, calcifying an exposed tooth pulp, and calcifying
the base or all of a pit or fissure in a tooth. The methods
comprise administering a composition comprising, or more
particularly consisting essentially of, an arginine (or equivalent
guanidinium) salt and calcium carbonate (or an equivalent poorly
soluble calcium salt), wherein a pH of the composition ranges from
about 7.5 to about 9.5, to the affected area.
[0017] Thus, it is an object of the invention to provide a
composition suitable to calcify dental lesions.
[0018] The invention has as a further object a composition for
reducing dentinal sensitivity.
[0019] Another object of the invention is to provide methods for
calcifying dental lesions, including dentinal tubules, exposed
tooth pulp, carious lesions, and pits or fissures.
[0020] These and other objects of the invention have been achieved
as further elaborated in the accompanying Drawings, Detailed
Description of the Invention, and Examples.
BRIEF DESCRIPTION OF DRAWINGS
[0021] FIG. 1. Titration of artificial dentinal fluid with arginine
bicarbonate (ArgHCO.sub.3) solution.
[0022] FIG. 2. Titration of artificial dentinal fluid with the
supernatant of an arginine bicarbonate/calcium carbonate powder
suspension.
[0023] FIG. 3. Titration of artificial dentinal fluid with the
supernatant of a calcium carbonate (CaCO.sub.3) suspension.
[0024] FIG. 4. Titration of artificial dentinal fluid with sodium
hydroxide (NaOH) solution.
[0025] FIGS. 5A and 5B. Scanning electron photomicrograph showing
(A) dentinal tubules after exposure to arginine bicarbonate/calcium
carbonate powder suspension, and (B) control prior to exposure.
[0026] FIGS. 6A and 6B. Scanning electron photomicrograph showing
(A) dentinal tubules after exposure to calcium carbonate powder
suspension, and (B) control prior to exposure.
[0027] FIGS. 7A and 7B. Scanning electron photomicrograph showing
(A) dentinal tubules after exposure to arginine bicarbonate, and
(B) control prior to exposure.
DETAILED DESCRIPTION OF THE INVENTION
[0028] The present invention has identified an oral composition
unlike the oral compositions previously identified, capable of
reducing or preventing dentinal hypersensitivity. It has been
discovered by the present invention that an oral composition
containing, and preferably consisting essentially of, arginine
bicarbonate (or equivalents thereof) and calcium carbonate (or
equivalents thereof) promotes the formation of dentinal tubule
plugs aided by combining calcium and phosphate in the fluid. It has
also been discovered by the present invention that an oral
composition containing arginine bicarbonate and calcium carbonate
promotes the formation of salivary precipitin, a
carbohydrate-protein-calcium phosphate complex present primarily in
dental plaque, which is formed from saliva when salivary proteins
combine with calcium and phosphate, to reduce or prevent dentinal
hypersensitivity.
[0029] Arginine bicarbonate and calcium carbonate are the preferred
components of compositions of the invention. However, compounds
with equivalent or closely related properties can substitute for
arginine bicarbonate. Other arginine compounds that can be used
include, but are not limited to, arginine hydroxide, arginine
carbonate, arginine phosphate, and arginine organic phosphate.
Although arginine phytate may be used, preferably it is avoided
except at high pH. Arginine bicarbonate is a guanidinium alkaline
carbonate salt; other such salts may be used in its place. Examples
include aminoguanidine and aminoguanidinium analogues.
[0030] Also, calcium compounds with equivalent or closely related
solubilities can substitute for calcium carbonate or part of it.
These include monocalcium phosphate, dicalcium phosphate,
tricalcium phosphate, calcium fluoride, calcium
monofluorophosphate, sodium calcium pyrophosphate, calcium laurate,
and calcium palmitate.
[0031] Thus, the present invention relates to a method of reducing
or preventing tooth hypersensitivity by delivering into the oral
cavity an oral composition containing a therapeutically effective
amount of arginine bicarbonate and calcium carbonate distributed in
an oral vehicle. The amount of arginine bicarbonate and calcium
carbonate sufficient to reduce or prevent dentinal hypersensitivity
is an amount sufficient to promote dentinal plugging. It has been
discovered that arginine bicarbonate and calcium carbonate promote
the formation of and provide particles in the oral cavity for
plugging the dentinal tubules of teeth. By plugging the dentinal
tubules, the oral compositions used in the method of this invention
are capable of reducing dentinal hypersensitivity. A mixture of
arginine bicarbonate, which is highly soluble, with poorly soluble
calcium carbonate (or calcium phosphate) yields a composition that
gives a pH of about 8.0 to 9.0, which is ideal for tubule plugging.
Calcium carbonate is a poorly soluble calcium salt which is defined
here as one having a solubility of about 0.1 to about 100 mg in 100
ml of water at room temperature near or above a pH of about 5, and
especially above neutral pH.
[0032] Arginine bicarbonate and calcium carbonate are well suited
for promoting dentinal plugging for a number of reasons. For one
thing, they are effective neutralizers of acid especially since
they can lose carbon dioxide and produce arginine hydroxide
(arginine free base) and calcium hydroxide, respectively, when they
come in contact with acid; this and being alkaline salts results in
a rapid and substantial rise in the pH that is particularly
favorable to deposit formation.
[0033] A second reason is that calcium carbonate is poorly soluble
above neutrality but is progressively more soluble as the pH
becomes acidic. This behavior is similar to that of the calcium
phosphate in tooth mineral tissues, thereby enabling the calcium
carbonate to provide a renewable reservoir of calcium to reduce or
prevent erosion of the cementum and dentine.
[0034] A third reason is that arginine bicarbonate surprisingly has
adhesive properties particularly useful at a pH ranging from about
7.5 to about 9.5, and preferably 8 to about 9 or 9.5. Together with
the poor solubility of calcium carbonate or a like calcium salt,
the arginine bicarbonate combination favors plugging of open
dentinal tubules by binding of calcium carbonate particles and
their attachment to the tubule walls and tooth surface.
Demonstration of plugging effectiveness in an actual dentine
plugging model shows the arginine bicarbonate/calcium carbonate
combination is significantly superior. This means of plugging
tubules is different from the prior art, where formation of tubule
plugs is attempted by producing calcium phosphate precipitates from
acidic solutions of moderately to highly soluble calcium and
phosphate salt solutions or the like.
[0035] Dentinal sensitivity resulting from the acids generated by
bacteria is really an early stage in the development of a dental
caries lesion. The bacteria found at the distal ends of tubules
exposed to the oral environment are the same as those found in
dental plaque.
[0036] Consequently, the preferred bicarbonate cation is arginine
since it will favor the base forming metabolism and the growth of
arginolytic rather than non-arginolytic bacteria. The former are
more alkalogenic and less cariogenic than the non-arginolytic
bacteria. This additional factor will ensure sustenance of an
elevated pH and a reservoir of alkali generation capability within
and in association with the dentinal tubules.
[0037] The preferred composition of arginine bicarbonate combined
with calcium carbonate has a number of effects. It neutralizes any
acid in the tubules, ensures a pH above neutrality and as high as,
and in a specific embodiment greater than, about 9.0, provides
needed calcium ions, provides a poorly soluble salt that has a
small particle size to facilitate filling and plugging the dentinal
tubules, and provides arginine to favor growth of and alkali
production by alkalogenic bacteria for maintenance of an alkaline
pH. Moreover and most importantly, arginine bicarbonate in the
preferred pH range of use has been found unexpectedly to have
adhesive properties that favor tubule plugging, an important
property in light of the fact that in vivo flow of dentinal fluid
out of the dentinal tubules under pressure makes any plugging
difficult.
[0038] As used herein, the terms "about" and "approximately" mean
within 20%, preferably within 10%, and more preferably within 5% of
a given value, unless another definition is provided.
Compositions
[0039] The present invention provides an oral composition
containing therapeutic amounts of arginine bicarbonate and calcium
carbonate distributed in an acceptable oral vehicle. The oral
compositions of this invention by weight may contain, for example,
arginine bicarbonate in a concentration ranging from about 1 to
about 25% and calcium carbonate in a concentration ranging from
about 5 to about 50%. In one embodiment, the oral composition
further contains a therapeutically effective amount of fluoride,
for example, 10 to 1500 ppm. Any conventional ingredients for the
particular oral vehicle may further be added to the oral
compositions of the present invention.
[0040] The pH of the oral compositions of the present invention
generally ranges from about 7.5 to about 9.5, preferably from about
8.0 to about 9.0, where arginine bicarbonate exhibits adhesive
properties. The pH of the oral compositions described herein can be
lowered with arginine bicarbonate or acid such as hydrochloric, or
raised with arginine hydroxide (arginine free base) or bases such
as sodium hydroxide or buffering agents such as sodium bicarbonate.
In addition to arginine bicarbonate and calcium carbonate, the oral
compositions of this invention may contain any conventional
ingredient for the particular oral vehicle discussed herein.
[0041] The amount of calcium carbonate and arginine bicarbonate
sufficient to reduce or prevent dentinal hypersensitivity varies
with the type of oral vehicle used to deliver the therapeutic
agent. Generally, the oral vehicles described by the present
invention contain between approximately 5 grams to 50 grams of
calcium carbonate and between approximately 1 gram to 25 grams of
arginine bicarbonate per 100 grams oral composition. In a further
embodiment of the present invention, the oral compositions used in
the method of this invention contain a therapeutically effective
amount of fluoride. The concentration of fluoride generally ranges
from approximately 10 to 1500 ppm. Calcium fluoride is a preferred
form of fluoride because it can be incorporated into a tubule plug
along with calcium carbonate largely as particles, where fluoride
ions along with calcium ions can be slowly released over prolonged
periods of time. Despite its low solubility, calcium fluoride
provides a source of calcium and fluoride ions and the ability to
develop a less acid soluble tubule plug than if absent.
[0042] Acceptable oral vehicles include any conventional oral
delivery system, such as dental care products, food products, and
chewing gum. Examples of dental care products include, for example,
dentifrices, topical solutions or pastes, mouthwashes in the form
of liquids or sprays or slurries, powders, gels or tablets, and
dental flosses. Examples of food products which may contain oral
compositions described herein include, for example, lozenges and
confections.
[0043] In addition to arginine bicarbonate and calcium carbonate,
the oral compositions described in accordance with the present
invention may contain any conventional ingredient for the
particular oral vehicle. For example, liquid mouthwashes may
contain solvents such as distilled or deionized water and ethanol;
a sweetening agent such as saccharine, aspartame, sorbitol,
mannitol, and xylitol; and a flavoring agent such as peppermint oil
and spearmint oil (see U.S. Pat. Nos. 4,226,851 and 4,606,912).
Dentifrices may contain, for example, a conventional abrasive such
as resins, silica, and insoluble alkali metal metaphosphates in a
standard amount of about 20% to about 60% by weight; a binder such
as hydroxyethylcellulose, xanthin gum, and sodium
carboxymethylcellulose in a standard amount ranging from about 0.5%
to about 5.0% by weight; a foaming agent such as sodium lauryl
sulfate, sodium coconut monoglyceride sulfonate, and
sodium-N-methyl-N-palmitoyl taurine in a standard amount ranging
from about 0.5% to about 3.0% by weight; a flavoring agent; a
sweetening agent; an antiseptic agent and any other ingredient
required for the particular composition as recognized by those
skilled in the art (see U.S. Pat. Nos. 4,177,258 and 4,721,614).
Tablets and powders may contain, for example, a vehicle such as
lactose and mannitol, a binder such as corn starch and
carboxymethylcellulose, and a disintegrator.
[0044] A dentifrice or paste for localized application to a
sensitive tooth site such as breeched cementum of an orally exposed
root surface may be one that is simpler in composition and applied
with a soft applicator. Such a dentifrice or paste may or may not
contain conventional abrasive, foaming agent, and flavoring agents.
Localized sites such as the dentine following tooth preparation for
a dental restoration would also involve simpler compositions and
include fillers used in dental pulp cappings, cavity liners and
cements and any other ingredients required for the composition by
those skilled in the art (Craig et al., 1989, Restorative Dental
Materials. Mosby, St. Louis, pp. 189-225). For example, zinc oxide
and eugenol at levels of (20 and 25%, respectively) would be
appropriate for dental cement compositions.
[0045] The oral compositions described herein may be produced by
adding arginine bicarbonate having a concentration by weight
ranging from about 1 to about 25% and calcium carbonate having a
concentration by weight ranging from about 5 to about 50% to an
acceptable oral vehicle using conventional techniques. The pH of
the composition may range from approximately 7.5 to approximately
9.5, preferably approximately 8.0 to approximately 9.0. The amount
of arginine bicarbonate and calcium carbonate to retard or prevent
dentinal hypersensitivity is an amount sufficient to plug the
exposed dentinal tubules in teeth in the oral cavity by promoting
the formation of dentinal plugs. For example, a dentifrice or paste
may contain arginine bicarbonate and calcium carbonate in a
concentration ranging from about 1 to about 25% and about 5 to
about 50%, respectively. A mouthwash or slurry may also contain
arginine bicarbonate and calcium carbonate in a concentration
ranging from about 1 to about 25% and about 5 to about 50%,
respectively.
[0046] The present invention further provides an article of
manufacture comprising a packaging material and the oral
compositions described herein contained within said packaging
material, wherein said oral composition is effective in retarding
or preventing dentinal hypersensitivity and wherein said packaging
material contains a label that indicates that said oral composition
is effective in retarding or preventing dentinal hypersensitivity.
The packaging material used to contain the oral compositions can
comprise glass, plastic, metal or any other suitably inert
material. For example, dentifrice containing the oral composition
of the present invention may be contained in a collapsible tube,
typically aluminum, line lead or plastic or a squeeze pump or
pressurized dispenser to measure out the contents or in a tearable
sachet.
[0047] The oral composition of the present invention may also be
used in a prophylaxis paste for polishing teeth or treating
sensitive teeth or preventing the development of sensitive teeth
after scaling, root planing or stain removal by a dentist or
hygienist, in a small dental container, such as a tub of a size
that permits easy access of the rotary attachments used in dental
offices on dental hand-pieces.
Methods
[0048] The present invention is directed to a method for promoting
the formation of dentinal tubule plugs by delivering into the oral
cavity an oral composition containing arginine bicarbonate and
calcium carbonate. The present invention is further directed to a
method for promoting the formation of salivary precipitin in the
oral cavity by delivering into the oral cavity an oral composition
containing arginine bicarbonate and calcium carbonate. In addition
to arginine bicarbonate and calcium carbonate, the oral
compositions used in this method may contain any conventional
ingredient for the particular oral vehicle as outlined above. In
another embodiment of this invention, the oral compositions used in
this method contain a therapeutically effective amount of fluoride,
generally between about 10 to about 1500 ppm. In one embodiment,
the oral compositions contain arginine bicarbonate in an amount
ranging from about 1 to about 25% and calcium carbonate in the
amount ranging from about 5 to about 50%,
RELATED USES OF COMPOSITIONS OF THE INVENTION
[0049] In related applications, tubule plugging with arginine
bicarbonate/calcium carbonate to stop dentinal fluid flow is
desirable to enable proper placement of a non-leaking cavity liner,
dental filling, or crown. Wetness, because of leakage of dentinal
fluid, will often result in poor sealing of these devices or
appliances. This is why sensitivity often persists and does so
until natural tubule plugging or tooth pathology and demise occurs.
Powder compositions of arginine bicarbonate/calcium carbonate
provided in slurries or pastes are suitable for the formation of
tubule plugs and use as a cavity lining material. Since dentinal
fluid is derived from pulpal fluid, the arginine
bicarbonate/calcium carbonate composition can provide the exposed
pulp with a capping at the same time that adjacent open tubules are
plugged.
[0050] A related application is the calcification or mineralization
of pits and fissures, which are sites where oral stimuli have
access to underlying dentinal tubules because the enamel at their
bases or sides is breeched as a result of tooth formation
deficiencies or because of dental caries. Here, one can scoop or
clean out the organic material in the pit or fissure with
mechanical devices, and add arginine bicarbonate/calcium carbonate
composition before placing a dental sealant or other filling
thereon.
[0051] Cavities deep enough to reach dentine exhibit sensitivity
because they often involve open dentinal tubules. Inserting powder
or paste compositions into carious lesions plugs these tubules and
at the same time calcifies, hardens, and seals off difficult to
remove carious material, a related application of this invention.
Calcification of exposed tooth pulps can also be accomplished. Like
dentinal fluid, pulp fluid (which is the source of dentinal fluid)
contains calcium and phosphate so that it is amenable to
calcification and sealing off the pulp from the oral environment.
Once more, because of the alkaline pH and calcium provided, a
slurry or paste containing arginine bicarbonate/calcium carbonate
to an exposed pulp will suffice. This can also be placed into a
pulp chamber from which pulp tissue has been removed.
[0052] In order to further illustrate the present invention, the
experiments described in the following examples were carried out.
It should be understood that the invention is not limited to the
specific examples or the details described therein.
EXAMPLE 1
Conditions for Intrinsic Plug Formation
[0053] None of the prior art methods described above have used
compositions that stimulate intrinsic blockage of the dentinal
tubule. In this case, formation of a deposit uses tubule contents.
Being a tissue fluid, dentinal fluid contains calcium and phosphate
ions, which makes it amenable to calcification.
[0054] In order to determine the conditions that promote intrinsic
plug formation, we performed the following experiments. We prepared
a solution comprised of the ions present in dentinal fluid (which
acted as artificial dentinal fluid) and progressively added
(titrated) various solutions thereto to determine the conditions
and substances conducive to the formation of aggregates (i.e.,
dentinal plugs). Aggregation was determined by means of measurement
of the absorbance with a spectrophotometer. From this, it was clear
that at a pH of 8.5 and above, aggregation of dentinal fluid
constituents occurred with arginine bicarbonate (FIG. 1), and was
enhanced by the addition of calcium carbonate (FIG. 2). Calcium
carbonate by itself was not sufficient to produce deposit formation
(FIG. 3), nor could one induce deposition by elevation of the pH as
with addition of sodium hydroxide (FIG. 4) or sodium bicarbonate.
Desirable precipitation was achieved by simultaneously raising the
pH with highly soluble arginine bicarbonate and providing calcium
from poorly soluble calcium carbonate (to supplement the calcium in
dentinal tubule fluid), which calcium carbonate also acted as a
filler material as described above to increase the ability to
achieve tubule plugging. The 2 to 5 .mu.m particle size of the
calcium carbonate was small enough to easily enter the dentinal
tubules and reduce the amount of precipitate needed to produce a
stronger and more complete plug.
[0055] A composition of arginine bicarbonate, which is highly
soluble, with poorly soluble calcium carbonate yielded a pH between
about 8.5 and about 9.0, which is highly favorable for tubule
plugging.
EXAMPLE 2
In Vivo Model of Tubule Plugging
[0056] A device developed by Greenhill and Pashley (J. Dental
Research, 60:686-698, 1981) that enables simulation of dentinal
tubule plugging in vivo was used to assess the effectiveness of the
invention. Dentine discs that varied in thickness from 0.6 to 0.8
mm were cut with a Buhler Isomet saw from extracted caries-free
molar teeth. They were then etched with 6% citric acid for two
minutes to remove the smear layer and stored in 70% ethanol until
used. A disc was mounted in the chamber of the apparatus with
occlusal side facing upwards. The occlusal side is determined by
passing light through a plastic grid beneath the section and
observing the section with a dissecting microscope. The tubules
appear further apart with the occlusal side up because of the lower
tubular density of the dentine occlusally (Walton et al., J. Dental
Research 55:639-642, 1976). Hydraulic conductance of fluid through
the discs was determined as described by Greenhill and Pashley,
supra.
[0057] Fluid containing levels of ions present in serum (Merck
Manual, 1972) was used to perfuse the disc. Their concentrations in
mM were as follows: Na--140.5, K--4.31, Ca--2.5, Mg--1.0, P--1.3.
The pH of this solution is raised to 7.0 with sodium hydroxide. The
solution was filtered through a 0.22 mm filter (Millipore Corp.,
Marlborough, Mass. 01752) prior to use to remove any bacteria
present. This solution is called artificial ionic dentinal fluid
(AIDF). Hydrostatic pressure was created by a fluid reservoir
leading via a glass capillary tube into the pulpal side of the
chamber at a level 30 cm above that of the surface of the
horizontally positioned disc. The distance traveled by an air
bubble positioned in the AIDF in the capillary tubing between this
pressure head and the pulpal side of the disc in a fixed period of
time was converted to hydraulic conductance values in ml cm.sup.-1
min.sup.-1 cm H.sub.20.sup.-1.
[0058] Sections were exposed to an arginine bicarbonate/calcium
carbonate mixture and various controls as follows. First, 400 ml of
AIDF was applied to the upward facing occlusal side of the section
and AIDF was allowed to flow through the disc from the pulpal side
for a period of five minutes. The distance that the air bubble
moved inside the capillary on the pulpal side of the chamber was
measured so that the rate of fluid movement through the disc could
be calculated and converted to hydraulic conductance values. This
procedure was repeated two more times or until a uniform flow rate
was achieved on three consecutive runs. The AIDF was then replaced
by 400 .mu.l of a 1:4 arginine bicarbonate/calcium carbonate slurry
and brushed on the dentine surface for two minutes. Next, the
mixture was removed with a pipette, washed three times with 400
.mu.l of deionized water and replaced with AIDF. The AIDF was
allowed to flow through the dentine slice and hydraulic conductance
readings were made at selected times up to 90 minutes.
[0059] New dentin sections were selected and the experiment
repeated using either (i) sodium bicarbonate plus calcium carbonate
in the same ratio as the arginine bicarbonate/calcium carbonate
mixture, (ii) arginine bicarbonate alone, (iii) sodium bicarbonate
(iv) calcium carbonate alone, or (v) distilled water.
[0060] Table 1 shows the results. The hydraulic conductance fell
the most with the arginine bicarbonate/calcium carbonate mixture.
Calcium carbonate, arginine bicarbonate, distilled water and
combining sodium bicarbonate and calcium carbonate had much smaller
effects, in some cases, a negative result (i.e. an increase in
conductance) was seen. Examination of the discs by scanning
electron microscopy revealed substantial blockage of the orifices
of the dentinal tubules with the arginine bicarbonate/calcium
carbonate mixture but little or no blockage with the other test
substances shown in the table. Blockage of dentinal tubules is
considered central to reduction of dentinal hypersensitivity.
TABLE-US-00001 TABLE 1 Percent Reduction in Hydraulic Conductance
Minutes after exposure Test Compounds 0 15 30 45 60 75 90 arginine
bicarbonate + 0 13.7 23.3 28.1 30.8 34.9 35.6 calcium carbonate
sodium bicarbonate + 0 -36.1 -27.8 -31.3 -34.0 -31.3 -28.5 calcium
carbonate arginine bicarbonate 0 11.7 15.6 14.4 14.5 16.1 16.1
sodium bicarbonate 0 -10.6 -1.0 7.2 11.5 15.9 19.7 calcium
carbonate 0 -18.5 -12.3 -5.5 -4.1 5.5 5.5 water 0 2.0 1.0 5.6 8.1
8.1 8.1
EXAMPLE 3
Adhesive Properties of the Plugging Composition
[0061] Arginine bicarbonate has adhesive properties desirable for
plugging dentinal tubules. Arginine bicarbonate is prepared from
arginine (free base) by titrating the arginine with gaseous carbon
dioxide as follows. 7.5 g of arginine is dissolved in 50 ml of
deionized water and has a pH of about 10.6. Then carbon dioxide is
delivered thereto under pressure (2 lbs./sq. in.) from a commercial
gas cylinder until a solution pH of 7.2 is reached. This is the pH
at which the carbon dioxide has converted all or most of the
arginine to arginine bicarbonate. For intrinsic plugging and the
formation of salivary precipitin, a pH between 8 and 9 is
preferred. This is done by titrating the arginine with carbon
dioxide to a desired pH between 8 and 9 or by mixing of the
arginine bicarbonate with the more alkaline arginine free base to a
desired pH between 8 and 9. The adhesive properties of arginine
bicarbonate are retained as well as the ability to produce
intrinsic plugging and promotion of salivary precipitin
formation.
[0062] Scanning electron micrographs show the ability of arginine
bicarbonate plus calcium carbonate to plug open dentinal tubules
(FIG. 5A) compared to calcium carbonate alone (FIG. 6A) and
arginine bicarbonate alone (FIG. 7A). Control samples (FIGS. 5B,
6B, 7B) were photographed prior to exposure to arginine bicarbonate
plus calcium carbonate or either compound alone. Thus, although
calcium carbonate is a poorly soluble calcium salt, its small
particle size and interaction with arginine bicarbonate make the
combination suitable for plugging open dentinal tubules.
[0063] The present invention is not to be limited in scope by the
specific embodiments described herein. Indeed, various
modifications of the invention in addition to those described
herein will become apparent to those skilled in the art from the
foregoing description and the accompanying figures. Such
modifications are intended to fall within the scope of the appended
claims.
[0064] All patents, patent applications, publications, and other
materials cited herein are hereby incorporated herein reference in
their entireties.
* * * * *