U.S. patent application number 14/314381 was filed with the patent office on 2014-10-09 for compositions for dental care.
The applicant listed for this patent is Nevada Naturals Inc.. Invention is credited to Anthony Joseph Sawyer, Richard F. Stockel, Anthony Errol Winston.
Application Number | 20140303100 14/314381 |
Document ID | / |
Family ID | 51228997 |
Filed Date | 2014-10-09 |
United States Patent
Application |
20140303100 |
Kind Code |
A1 |
Winston; Anthony Errol ; et
al. |
October 9, 2014 |
COMPOSITIONS FOR DENTAL CARE
Abstract
This invention pertains to dental care compositions with
antimicrobial benefits. In particular, the invention provides for
compositions of oral tissue-adherent salts that release biocidal
ions on a controlled release basis and thereby provide and maintain
an essentially uniform concentration of biocidal ions above the MBC
or MIC of the target bacteria at the site of application in the
mouth for an extended period of time. The compositions are useful
for treating or preventing oral diseases resulting from bacteria,
fungal or yeast infections, such as caries, gingivitis, periodontal
disease and candidiasis. 13
Inventors: |
Winston; Anthony Errol;
(East Brunswick, NJ) ; Stockel; Richard F.;
(Bridgewater, NJ) ; Sawyer; Anthony Joseph;
(Albuquerque, NM) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Nevada Naturals Inc. |
Albuquerque |
NM |
US |
|
|
Family ID: |
51228997 |
Appl. No.: |
14/314381 |
Filed: |
June 25, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13200997 |
Oct 6, 2011 |
8795638 |
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14314381 |
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11599758 |
Nov 15, 2006 |
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13200997 |
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10647752 |
Aug 26, 2003 |
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11599758 |
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12589155 |
Oct 19, 2009 |
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13200997 |
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11633231 |
Dec 4, 2006 |
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13200997 |
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10770248 |
Feb 2, 2004 |
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11633231 |
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10972567 |
Oct 25, 2004 |
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11633231 |
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12798479 |
Apr 5, 2010 |
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13200997 |
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12586695 |
Dec 22, 2009 |
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12798479 |
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11517147 |
Sep 7, 2006 |
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12586695 |
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10972567 |
Oct 25, 2004 |
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11517147 |
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10770248 |
Feb 2, 2004 |
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10972567 |
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61196455 |
Oct 17, 2008 |
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60748719 |
Dec 9, 2005 |
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60445104 |
Feb 6, 2003 |
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60719900 |
Sep 23, 2005 |
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Current U.S.
Class: |
514/24 ; 514/152;
514/154; 514/358; 514/551; 514/635; 514/643 |
Current CPC
Class: |
A61K 8/347 20130101;
A61K 6/30 20200101; A61Q 11/00 20130101; A61K 31/155 20130101; A61K
6/30 20200101; A61K 6/30 20200101; A61K 45/06 20130101; C08L 29/04
20130101; A61K 8/8135 20130101; C08L 33/10 20130101; C08L 71/02
20130101; C08L 29/04 20130101; C08L 31/04 20130101; C08L 33/10
20130101; C08L 71/02 20130101; A61K 6/30 20200101; C08L 31/04
20130101; A61K 8/43 20130101; A61K 6/20 20200101; A61K 6/30
20200101; A61K 6/30 20200101; A61K 31/14 20130101; A61K 6/30
20200101; A61K 6/30 20200101; A61K 6/30 20200101; A61K 31/4425
20130101 |
Class at
Publication: |
514/24 ; 514/635;
514/551; 514/358; 514/643; 514/154; 514/152 |
International
Class: |
A61K 31/4425 20060101
A61K031/4425; A61K 31/14 20060101 A61K031/14; A61K 45/06 20060101
A61K045/06; A61K 31/155 20060101 A61K031/155 |
Claims
1-21. (canceled)
22. A method of treating oral diseases in the mouth, said method
comprising the step of applying to the target area of the mouth an
oral treatment composition comprising a controlled release, oral
tissue-adherent salt comprising an anionic component with phenolic,
C8-C18 monocarboxylate, or polycarboxylate functionality and a
cationic component polymer or copolymer with quaternary ammonium,
guanidino, or biguanidino groups, as the cationic component,
whereby said salt has (i) an aqueous solubility from about 200 ppm
to about 10,000 ppm enabling it to release dissolved biocidal or
biostatic cations into the oral fluid at a concentration that is
equal to or exceeds the minimum bactericidal concentration (MBC) or
minimum inhibitory concentration (MIC) of the target bacteria,
while (ii) the aqueous solubility of said salt is appropriately
limited to leave undissolved, un-dissociated salt on the oral
tissues to which it was applied, to act as a reservoir to allow the
subsequent release of additional biocidal or biostatic ions into
the mouth, to replace the dissolved biocidal or biostatic ions as
they are used up or otherwise depleted, thereby maintaining an
essentially uniform concentration of biocidal biostatic ions equal
to or exceeding the MBC or MIC of the target bacteria in the oral
fluid in the treated area of the mouth for an extended period of
time.
23. The method of treating oral diseases of claim 22, in which the
oral treatment composition is applied to the soft or mineralized
oral tissue above the gum line as a supra-gingival treatment to
control bacteria, fungi and yeasts in the prevention and treatment
of dental caries, gingivitis, candidiasis or other oral
diseases.
24. The method of treating oral diseases of claim 22, in which the
controlled release, oral tissue-adherent salt is preformed or is
formed by application of two separate salt solution components, one
component containing the cation and one component containing the
anion, to the target area by physically segregating the two
components prior to use, then separately or simultaneously adding
the two components to the target area to form the salt in situ.
25. The method of treating oral diseases of claim 22, in which the
controlled release, oral tissue-adherent salt is delivered to the
teeth, gums, supra-gingival areas, or other area of the mouth in a
toothpaste, a tooth gel, a mouthwash, dental floss, a tray, a
treatment strip, an ointment, a dental appliance, a denture
appliance or other type device for delivery of the oral
tissue-adherent salt.
26. The method of treating oral diseases of claim 22, in which the
anionic component is selected from the group consisting of
phenolate, poly-phenolate, resorcinolate, PCMX anion, eugenol
anions, thymol anions, and penicillin anions and the cationic
component is selected from the group consisting of
polyquaterniunum4, polyquaternium-10, polyquaternium-11,
polyquaternium-22, polyquaternium-28, polyquaternium-32 and
polyquaternium-37 cations.
27. The method of treating oral diseases of claim 22, in which the
quaternary ammonium cationic component is selected from the group
consisting of cetylpyridinium ions, benzalkonium ions, and
benzethonium ions.
28. The method of treating oral diseases of claim 22, in which the
biguanidino cationic component is chlorhexidinium cation.
29. The method of treating oral diseases of claim 22, in which the
guanidino cationic component is N.alpha.-C8-C18)acyl(C2-C18) alkyl
ester of a dibasic amino acid cation.
30. The method of treating oral diseases of claim 22, in which the
polycarboxylate anionic component is selected from the group
consisting of anions of malic acid, maleic acid, fumaric acid,
tartaric acid, succinic acid, adipic acid, malonic acid, citric
acid, polyacrylic acid, alginic acid, xanthan, polysaccharide and
vinyl ether/maleic acid copolymer.
31. The method of treating oral diseases of claim 22, in which the
cation component is selected from the group consisting of cations
of tetracycline, aureomycin, terramycin, tigecycline, doxycycline,
minocycline, demeclocycline, lymecycline, meclocycline,
methacycline, rolitetracycline, and clindamycin.
Description
REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of application
Ser. No. 11/599,758, filed Nov. 15,2006 (which is a
continuation-in-part and claims the benefit of application Ser. No.
10/647,752, filed Aug. 26, 2003), the disclosure of which is
incorporated herein in its entirety. This application claims the
benefit of application Ser. No. 12/589,155, filed Oct. 19, 2009
(claiming the benefit of provisional application Ser. No.
61/196,455, filed Oct. 17, 2008) and also claims the benefit of
application Ser. No. 11/633,231, filed Dec. 4, 2006 (claiming the
benefit of provisional application Ser. No. 60/748,719 filed Dec.
9, 2005). Further, this application claims the benefit of
application Ser. No. 10/770,248 filed Feb. 2, 2004 (claiming the
benefit of provisional application Ser. No. 60/445,104 filed Feb.
6, 2003) now abandoned and also claims the benefit of application
Ser. No. 10/972,567 filed Oct. 25, 2004 as a continuation-in-part
of said application Ser. No. 10/770,248. Further, this application
claims the benefit of application Ser. No. 12/798,479 filed Apr. 4,
2010, which is a continuation-in-part of application Ser. No.
12/586,695 filed Sep. 26, 2009 which is a continuation-in-part of
application serial no. 11/517,147 filed Sep. 7, 2006, which claims
the benefit of provisional application Ser. No. 60/719,900 filed
Sep. 23, 2005. This application also claims the benefit of
application Ser. No. 10/972,567 filed Oct. 25, 2004 as a
continuation-in-part of said application Ser. No. 10/770,248 filed
Feb. 2, 2004. The disclosures of all of the foregoing applications
are incorporated by reference herein in their entirety.
FIELD OF THE INVENTION
[0002] This invention relates to oral care compositions and
formulations which deliver and maintain uniform concentrations of
antimicrobials to target areas in the mouth for an extended period
of time.
BACKGROUND OF THE INVENTION
[0003] It is important to prevent the deterioration of oral health
by maintaining good oral hygiene. However, there are many diseases
which can occur in the mouth, apparently despite good oral hygiene
practices. The diseases can seriously affect the health of oral
tissue. Oral diseases not only result in the destruction of oral
tissue but can also have systemic effects on the overall health of
the human body. Therefore early effective treatment of oral
infections is important.
[0004] Oral diseases are generally due to bacterial, fungal and
yeast infections. For example dental caries is due to bacterial
infections in the plaque biofilm on teeth. Cariogenic bacteria
produce acids, which cause the development of demineralized
subsurface lesions in mineralized tissue. These lesions grow in
size eventually developing into cavities in the crowns and roots of
teeth. If untreated, cavities can ultimately lead to the loss of
teeth.
[0005] Gingivitis is also due to pathogenic bacteria in plaque
biofilm. These bacteria produce toxins, which inflame the gingiva
and cause the gums to bleeds. Many experts believe that gingivitis
can lead to a more serious disease, periodontitis.
[0006] Periodontitis is also due bacterial infections. However, in
this case the infection is below the gum line. In this disease the
tissues around the roots of teeth become inflamed. The disease
leads to loss of attachment and the formation of periodontal
pockets. As the disease progresses there is loss of alveolar bone
and eventually loss of teeth.
[0007] Candida infections, also known as thrush, are due to yeast
infections and result in inflammation and the formation of
potentially painful lesions in the oral mucosa.
[0008] Mechanical oral health measures alone while helpful may not
be sufficient to maintain oral health. Often other medications are
required to control oral diseases and prevent adverse effects.
Since oral diseases are due to microbes, anti-microbial therapy can
be important in the control of oral infections. However, due to
their short residence time in the mouth topical application of
antimicrobials to the mouth is usually relatively ineffective in
eliminating the target bacteria.
OBJECTS OF THE INVENTION
[0009] It is an object of the invention to provide a safe and
efficacious composition that will have a broad spectrum of activity
against bacteria that are responsible for oral diseases and remain
in the mouth at effective concentrations for extended periods of
time.
[0010] It is a further object of the invention to provide a safe
and efficacious composition that is adherent to oral tissues and
releases and thereafter continuously maintains uniform
concentrations of antimicrobial agents in the area being
treated.
[0011] It is also an additional object of the invention to provide
formulations and delivery vehicles that allow biocidal and
biostatic compositions of the invention to be conveniently applied
to various regions of the mouth where needed.
DETAILED DESCRIPTION OF THE INVENTION
[0012] The foregoing objects of the invention and additional
objects are met by providing oral treatment compositions which are
adherent to oral tissues and which release even concentrations of
one or more biocidal or biostatic components for extended
periods.
[0013] Essentially the invention provides for an oral treatment
composition containing a controlled release, oral tissue-adherent
salt, comprising anionic and cationic components, either or both of
which have significant biocidal or biostatic activity, whereby said
salt has (i) an aqueous solubility enabling it to release dissolved
biocidal or biostatic cations or biocidal or biostatic anions into
the oral fluid at a concentration that is equal to or exceeds the
MBC or MIC of the target bacteria, while (ii) the aqueous
solubility of said salt is appropriately limited to leave
undissolved, un-dissociated salt on the oral tissues to which it
was applied, to allow the subsequent release of additional biocidal
or biostatic ions into the mouth and thereby replace the dissolved
biocidal or biostatic ions that are used up or otherwise depleted,
thereby maintaining an essentially uniform concentration of
biocidal or biostatic ions equal to or exceeding the MBC or MIC of
the target bacteria in the oral fluid for an extended period of
time.
[0014] As noted, the controlled release, oral tissue-adherent salts
employed comprise cationic and anionic components, one or other or
both of which are biocidal or biostatic to the target bacteria. The
controlled release properties of the salt are primarily influenced
by the solubility of the oral tissue-adherent salt. Thus, the salt
needs to be sufficiently soluble to release enough biocidal
component to exceed the minimum bactericidal concentration (MBC) or
minimum inhibitory concentration (MIC) of that component to the
target bacteria. However, the solubility of the salt should be such
that much of the applied oral tissue-adherent salt remains in
undissolved form to release additional biocidal component to
replace that used up or depleted from the target area.
[0015] Typically, the biocidal or biostatic cationic or anionic
components of the invention have MBCs in the range from about 0.1
ppm to about 1000 ppm against a broad range of bacteria. Hence in
order to be effective the solubility of the tissue-adherent salt
ideally needs to be at least about 5 ppm and up to about 2000 ppm
depending on the susceptibility of the target bacteria to the
biocidal ions. On the other hand, the solubility of the salt should
generally be no more than from about 200 ppm (0.02%) to no more
than about 10,000 ppm, (1%) to insure that a reservoir of
undissolved tissue-adherent salt remains at the site where it is
applied for an extended period of time.
[0016] The oral treatment composition comprises cationic and
anionic components at least one of which is biocidal or biostatic.
Biocidal cationic components of the invention preferably have
primary ammonium, secondary ammonium, tertiary ammonium, quaternary
ammonium, guanidino, or biguanidino functionality. Examples of
highly effective biocidal cations include but are not limited
to(C.sub.8-C.sub.18) alkyl dimethyl benzyl ammonium ions,
(C.sub.8-C.sub.18) alkyl trimethyl ammonium ions,
(C.sub.8-C.sub.18) dialkyl methyl benzyl ammonium ions,
(C.sub.8-C.sub.18) dialkyl dimethyl ammonium ions, benzalkonium
ions, benzethonium ions, sanguinarium ions, cetylpyridinium ions,
hexetidinium ions, alexidinium ions, chlorhexidinium ions,
octenidinium ions, polyhexamethylene biguanidino (PHMB) ions,
polyhexamethylene guanidino ions, and polyquaternium-2 ions.
[0017] In the preparation of oral tissue adherent salts, it is
especially desirable to utilize components which are derived from
natural renewable sources of ingredients. Compounds based on
renewable-sourced ingredients are generally safer to humans, being
completely metabolized by the body to non-toxic compounds, like
carbon dioxide and water. Many of these compounds are less
cyto-toxic and hence are less irritating to the skin, mucosa and
eyes. Additionally such compounds are also more fully biodegraded
in the environment and do not leave environmentally undesirable
residues. Examples of such naturally derived cations include
biocidal or biostatic cations of (i) a C.sub.8-C.sub.18 alkyl ester
of an mono-carboxylic amino acid, of a peptide, of carnitine, of
creatine and of glycine betaine, (ii) a C.sub.2-C.sub.18 dialkyl
ester of a dicarboxylic amino acid (iii) a C.sub.2-C.sub.18 alkyl
ester of a C.sub.8-C.sub.18 acyl ester of serine, threonine and
carnitine, (iv) a C.sub.8-C.sub.18 acyl ester of choline and (v) a
C.sub.1-C.sub.18 alkyl ester of a C.sub.2-C.sub.18 mono-acyl amide
of a dibasic amino acid or a polybasic peptide.
[0018] Of course, these compounds and be prepared form synthetic
sources and would retain many of the environmental and safety
benefits of their naturally derived analogues.
[0019] Another group of useful cationic component for the
controlled release, oral tissue-adherent salts are antibiotics with
cationic functionality. Examples include tetracycline, aureomycin,
terramycin, tigecycline, doxycycline, minocycline, demeclocycline,
lymecycline, meclocycline, methacycline, rolitetracycline, and
clindamycin. When the anionic component of the controlled release,
oral tissue-adherent salt is biocidal or biostatic, a cationic
component may be chosen which is biocidally inactive. In this case,
the cationic counter ion is selected on the basis of the solubility
of the resulting salt and how well the salt adheres to oral tissue.
Examples or inactive cations for this use include polyamine,
polyethyleneimine and polyammonium ions, various polymers and
copolymers with quaternary ammonium groupings including
polyquaternium-4 (Celquat.RTM.), polyquaternium-10,
polyquaternium-11, polyquaternium-22, polyquaternium-28,
polyquaternium-32 and polyquaternium-37.
[0020] Useful biocidal or biostatic anionic components for the
controlled release tissue adherent salt include anions with
phenolic functionality. Examples of these anions are phenolate,
resorcinolate, parachlorophenolate, trichlorophenolate (TCP anion),
o-phenylphenolate, the phenolate anion of
trichloro-hydroxy-diphenyl ether (triclosan anion), phenolate
anions of parachloro-metaxylenol (PCMX anion), phenolate ions of
thymol, 4-allyl-2-methoxy phenolate (eugenol anions),
hexachlorophenate anions and various polyphenolate anions.
[0021] Another group of useful biocidal anions include antibiotics
with anionic functionality. These include the anions of penicillin
and its derivatives.
[0022] When the cationic component of the controlled release tissue
adherent salt has biocidal of biostatic activity, the anionic
component maybe inactive. In this case the anion is selected on the
basis of the solubility of the resulting salt and its contribution
to the ability of the salt to stick to oral tissue surfaces.
Examples of such suitable anions include those with mono- or
polycarboxylate functionality. These include the anions of a
C.sub.8-C.sub.18 monocarboxylic acid. It has been found that the
solubility and oral tissue adherence of the resulting controlled
release oral tissue-adherent salt decreases with increasing number
of carbon atoms in the carboxylic acid. Another group of useful
anions include the anions of polycarboxylic acid such as malic
acid, maleic acid, fumaric acid, tartaric acid, succinic acid,
adipic acid, malonic acid, citric acid, polyacrylic acid, alginic
acid, xanthan, polysaccharide and vinyl ether/maleic acid
copolymer. One preferred group of controlled release, oral
tissue-adherent salts are the salts of a C.sub.8-C.sub.18
carboxylic acid with a N.sup..alpha.-(C.sub.8-C.sub.18) acyl
(C.sub.2-C.sub.18) alkyl ester of a dibasic amino acid selected
from the group arginine, lysine, ornithine and histidine. A
particularly preferred member of this group is the laurate salt of
N.sup..alpha.-lauroyl ethyl ester of arginine.
[0023] The controlled release, oral tissue adherent salts can be
prepared by any means. A particularly simple method is by the
metathesis reaction of two soluble salts to form the desired less
soluble target controlled release, skin adherent salt. Another
straightforward method of preparing the salts is by the direct
reaction of the anionic acid with the cationic base. The salts can
be preformed before incorporating them into compositions of the
invention. Alternatively the salts can be formed by application of
two separate salt solution components, one component containing the
cation and one component containing the anion, to the target area
to form the salt in situ, by physically segregating the two
components prior to use, then separately or simultaneously adding
the two components to the target area to form the salt. For
example, as a treatment for periodontitis, the salt can be formed
by metathesis directly within the gingival pocket by simultaneously
application of solutions of soluble salts each of which contains
the two ionic portions of the medicinal salt, so that it
precipitates in situ and adheres to the sub-gingival tissue.
Therefore one component containing the cation and one component
containing the anion can be formed in situ where needed at the
oral-tissue treatment target area by application of separate salts
of the anionic acid and cationic base.
[0024] The controlled release oral tissue-adherent salts may attach
themselves more effectively to mineralized tissue or to soft oral
tissue. For example, supra-gingival treatment salts may become
strongly attached to tooth enamel surfaces or to the gingival or
other mucosal surfaces. Sub-gingival treatment salts may most
effectively be attached to the dentin or to areas of sub-gingival
soft tissue.
[0025] Oral treatment compositions of the invention are useful for
treating and prevent any kind of bacterial, fungal or yeast based
infections of the mouth. Thus, when applied supra-gingivally, the
compositions of the invention can kill disease bacteria such as s.
mutans, s. sobrinus and lactobacilli which are responsible for
dental caries. Removal of cariogenic bacteria protects the teeth
against the formation of decalcified lesions and cavities. The
compositions are also effective in controlling bacteria responsible
for gingivitis and bleeding gums. Suitable controlled release,
tissue adherent salts are effective against fungal infections and
yeasts which cause candidiasis. When applied below the gumline
compositions of the invention are effective in controlling the
anaerobic bacteria responsible for periodontal diseases.
[0026] The compositions of the invention can be applied to the
teeth and gums in different forms. Toothpastes, gels, trays,
mouthwashes and irrigating devices are suitable for applying the
compositions to teeth and gums. Dental floss with these salts can
be used to ensure that the treatments get between teeth. Denture
appliances can be treated with compositions of the invention to
treat or prevent candidiasis. Compositions of the invention can
also be applied using a sub-gingival syringe for the treatment of
periodontal disease.
[0027] Since the controlled release, oral tissue-adherent salts
tend to have low aqueous solubility, when incorporated into
formulations such as toothpastes, gels and mouthwashes these salts
are either dispersed as fine particles into the formulation or
dispersed as micro-emulsions.
[0028] This invention thus also provides for a method of treating
oral diseases in the mouth, by the application to the target area
of the mouth of an oral treatment composition containing (1) a
controlled release, oral tissue-adherent salt comprising anionic
and cationic components, either or both of which have significant
biocidal or biostatic activity, whereby said salt has (i) an
aqueous solubility enabling it to release dissolved biocidal or
biostatic anions or biocidal or biostatic cations into the oral
fluid at a concentration that is equal to or exceeds the MBC or MIC
of the target bacteria, while (ii) the aqueous solubility of said
salt is appropriately limited to leave undissolved, un-dissociated
salt on the oral tissues to which it was applied, to act as a
reservoir to allow the subsequent release of additional biocidal or
biostatic ions into the mouth, to replace the dissolved biocidal or
biostatic ions as they are used up or otherwise depleted, thereby
maintaining an essentially uniform concentration of biocidal or
biostatic ions equal to or exceeding the MBC or MIC of the target
bacteria in the oral fluid in the treated area of the mouth for an
extended period of time.
EXAMPLES
[0029] The following non-limiting examples serve to illustrate the
various embodiments of this invention.
Example I
Dental Floss to Treat Gingivitis
[0030] To a 5 g sample of a chlorhexidine-triclosan complex was
added 60 g of PEG 3350, 30 g PEG 1000 and 5 g glycerin. The mixture
was gently heated and stirred to dissolve the complex. The
resultant warm solution was used to coat a commercial non-wax
dental floss to provide an efficacious germicidal dental floss. The
floss is used to treat gingivitis. When teeth are flossed the
controlled release salt is deposited between teeth. A synergistic
combination of chlorhexidine cations and triclosan anions is
gradually released reducing the interproximal plaque and reducing
the tendency for bleeding gums.
EXAMPLE II
Periodontal Composition to Treat Periodontitis
[0031] N.sup..alpha.-lauroyl arginine ethyl ester laurate salt (40
g) is melted with glycerin (60 g) at about 60.degree. C. and mixed
until a thick paste is formed. The paste is allowed to cool to room
temperature. The paste is used to treat periodontitius by applying
150 to 300 mg this paste into the periodontal pocket. After 2 days
the overall count of anaerobic bacteria measurably reduced. After
three weeks inflammation is reduced and there appear to be initial
signs of gum reattachment. Three months later pocket depth is
reduced by 2 mm and no inflammation is apparent.
EXAMPLE III
Antimicrobial Treatment For the Prevention of Caries and Gingivitis
in High Risk Populations
[0032] The following formulation is prepared
[0033] Part I
TABLE-US-00001 Cetyl pyridinium chloride 1.0 Water 50.0
[0034] Part 2
TABLE-US-00002 Carbomer 941 0.5 Water 48.5 Triethanolamine To pH
5.5
[0035] Cetyl pyridinium chloride is dissolved in cold deionized
water. A separate dispersion of Carbomer 941 is prepared in
deionized water at 60.degree. C. The cetyl pyridinium solution is
added with stirring to the Carbomer solution. Finally the pH of the
mixture is adjusted to between 4.5 and 6.0 using triethanolamine.
Cetyl pyridinium-carbomer salt controlled release, oral tissue
adhesive salt is formed in situ. The gel is topically applied to
teeth and gums using a swab to reduce bacterial counts of bacteria
causing dental caries and gingivitis.
EXAMPLE IV
Prevention and Treatment of Candidiasis
[0036] An orally acceptable cream containing 0.5% dodecyl dimethyl
ammonium thymolate is applied to the surfaces of dentures and other
oral appliances to eradicate candida infections thereon. The cream
can also be applied to the oral pallet, tongue and oral mucosa. It
is preferable to leave the cream in place for at least an hour
before eating, drinking or brushing teeth.
TABLE 1
Comparison of Several LAE Salts Against Two Common Oral Bacteria
Using a Zone of Inhibition Test
[0037] In Table 1, Agar plates were seeded with either S. mutans or
S. pyogenes and N.sup..alpha.-lauroyl arginine ethyl ester salts
("LAE salts") were applied. After 3 days, the plates were examined
for bacterial growth and the presence of a zone of inhibition
around the applied salt. For S. pyogenes, a reduction of zone of
inhibition size was seen with increasing size of the anion from
acetate to laurate, showing decreased bio-availability and
increased retention in the salt form. S. mutans shows no such
dependency, suggesting that maximal inhibition was achieved by the
material released from the laurate salt.
[0038] In Table 1, LAE-HCl was reacted with a series of fatty acids
of increasing molecular weight, which is proportional to
antimicrobial retention, but inversely-proportional to the
bioavailability of the free antimicrobial ion. In another words, a
pairing was developed, which would be soluble enough to release the
antimicrobial agent into the periodontal pocket at a concentration
which kills or inhibits the growth of periodontal bacteria, but
sufficiently limited to act as a reservoir for the release of
additional antimicrobial agent as the dissolved one gets used up or
is flushed from the area.
TABLE-US-00003 TABLE 1 Comparison of LAE salts against two common
oral bacteria Zone of Inhibition (mm) Sample # Compound S. mutans
S. pyogenes 1 LAE-hydrochloride salt 8 5 2 LAE acetate 8 10 3 LAE
lactate 7 6 4 LAE octanoate 5 3 5 LAE laurate 8 2
[0039] In order to determine whether the adhesive laurate ion would
interfere with the attachment and biological functions of cells, an
experiment was performed, in which the bottom of a cell culture
plate was coated with lauric acid and plated cells on top of it.
Microphotographs showed normal morphology cells homing in the
laurate-covered areas--24h after plating. Normally proliferating
cells were observed 11 days later beneath the laurate matrix
(scraped for clarity), indicating that at least in this model
system, the presence of lauric ion coating does not seem to be a
physical impediment to the periodontal regeneration.
[0040] Prototypes of N.sup..alpha.-lauroyl arginine ethyl ester
(LAE) salt and of a minocycline salt of lauric acid would carry an
added value of regenerative potential through inhibition of
inflammation-associated proteases, and through the release of
arginine--a well-known mediator of tissue repair--in the case of
LAE (Poiarkov et al., 2007, Debats et al., 2009).
* * * * *