Note: Descriptions are shown in the official language in which they were submitted.
-
1 3388~0
This application is a divisional of S.N.585,502 and relates to a method of cleaning a dental
prosthetic device whereas the parent relates to the use of a stabilized aqueous solution of
chlorine dioxide in the oral cavity.
IMPROVED METHOD AND COMPOSITION FOR PREVENTION OF
PLAOUE FORMATION AND PLAQUE DEPENDENT DISEASES
Backqround of the Invention:
1. Field of the Invention
The present invention is directed to a method and
composition for prevention and treatment of oral disease and,
more particularly, to the use of chlorine dioxide in aqueous
solution for preventing formation of plaque and treatment of
plaque dependent diseases
2. Description of the Prior Art
The volatile sulfur compounds, hydrogen sulfide (H2S)
methylmercaptan (CH3SH) and di-methylmercaptan (CH3)2S are
recognized in the current dental literature as being the major
contributors to oral malodor. Numerous researchers using
organoleptic, chemical, amperometric, mass spectrometric or gas
liquid chromatographic methods have demonstrated that these
volatile sulfur compounds are present in the head space and vapor
of putrefied saliva and in individual samples of mouth air. In
most persons, hydrogen sulfide and methylmercaptan constitute
over 90% of the total volatile sulfur content identified in mouth
air.
-
- ' 13388gO
These malodorous volatile sulfur compounds are
generated primarily through the putreficative action of oral
microorganisms on sulfur cont~; ni ng amino acids, peptones or
proteins found in the mouth. These substrates are readily
available in saliva and dental plaque or may be derived from
proteinaceous food particles trapped between the teeth, in the
gingival crevice or adhering to the mucous membranes and the
irregular surface of the tongue as well as exfoliated oral
epithelium, food debris and the like. Current studies have
indicated that mouth odor not only comes $rom the posterior
dorsal surface of the tongue but also from periodontal pockets.
People with periodontal involvement have an attendant increase in
oral malodor from disintegrated epithelial cells.
Starting with a clean tooth surface, plaque formation
and resulting ecology occurs in the following steps:
1. Deposition of a coating of glycoproteins from
salivary and other oral mucous gland secretions. This is
referred to as acquired pellicle.
2. Fastening and colonization of streptococcus
organisms to the acquired pellicle, primarily by streptococcus
sanguis and streptococcus mutans.
3. Conversion of sucrose to glucans (dextran) and
fructans by the bacterial enzyme glucosyltransferases. In this
plaque mass are embedded dead cells, cell debris and food debris.
High molecular weight polymers of glucose and other sugars,
altered salivary glycoproteins, proteases and various chemotactic
:13388~0
and inflammatory inducing substances have been detected and
partially characterized.
4. Other organisms, primarily gram positive aerobes,
become residents in the plaque mass and use the glucans and
fructans for nutrition. These are primarily oxygen using
organisms and the oxygen source is from the saliva that bathes
the plaque mass.
5. With time and the functioning of this ecological
system, the oxygen use by the superficial bacteria deprive the
lower layers of the plaque matrix of a supply of oxygen. An
opportunity for non oxygen using bacteria (facultative anaerobes)
to become established is provided.
6. If left undisturbed, the ecological system now
established is self perpetuating. That is, the streptococcus
bacteria continue to produce glucans and fructans. Other
bacteria produce toxins that kill cells of the host and the dead
cells become other essential nutrients. The superficial bacteria
deprive the deeper layers of the plaque mass of oxygen and keep
the ecological system going. Thus, both aerobic and anaerobic
organisms survive in the plaque mass.
7. The established ecological system attendant the
plaque mass produces toxins from the aerobic bacteria that cause
gingivitis and toxins from the anaerobic bacteria that cause
periodontitis.
Various substances have been tested for their ability
1338890
to disrupt plaque or prevent its formation and to treat mouth
odor, such as antibiotics, chlorhexdines, oxine and alexidine.
The prior art compositions that have been used and
tested have found some acceptance but are generally ineffective
in periodontitis, gingivitis, plaque accumulation and mouth
malodor. Accordingly, there exists a clear need for composition
which will effectively inhibit the initial pellicle which
precedes plaque formation and inhibit or control the formation of
bacterial plaque and suppress organisms such as but not limited
to (1) Streptococcus Mutans, which is implicated as the major
cause of human dental decay; (2) Black Pigmented Bacteroides, an
Actinobacillus Actinomycetumcomitans which is implicated in human
periodontitis; and (3) will reduce odor intensity in the mouth
through the control of hydrogen sulfide and methylmercaptan.
SummarY of the Present Invention
The present invention contemplates the use of
stabilized chlorine dioxide in aqueous solution for the treatment
of the mouth as a deodorizing agènt, anti-plaque agent,
bactericide for treatment of gingivitis and periodontitis and as
a bactericidal, fungicidal and viralcidal agent in other related
applications. In the present invention a composition cont~;n;ng
stabilized chlorine dioxide may be used for treatment of the
mouth either in a solution, for example, as a mouthwash or in a
dentifrice generally in concentrations of below approximately
0.2% for the control of odorgenic microorganisms, bacterial
- ` 1338890
plaque, gingivitis and bacteria which cause these conditions.
Similarly, chlorine dioxide is also effective as a cellular
debridement agent following surgical procedures and sanitizer
denture soak and as a contact lens soak The use of chlorine dioxide
and its effects on man has been clinically evaluated. The relative
safety of oral ingestion of chlorine dioxide was ~e~o~trated
extensively in ~nim~l s and later in hllm~n~ by hubbers, Chauan and
Bianchine, Environmental Health PersPectives, Volume 46, Pages 57-62,
1982
Description of the Preferred Embodiment
Chlorine dioxide, Cl02, functions biochemically in many
ways other than as a germicide. These functions include: (1)
oxidation of double bonds between two carbon atoms; (2) oxidation
of unsaturated fatty acids (lipids) via double bonds between two
carbon atoms; (3) acceleration of hydrolysis of carboxalic
anhydrides; (4) oxidation of aldehydes to the corresponding
carboxalic acids; (5) oxidation of alcohols; (6) oxidation of
amines; (7) oxidation of phenols, phenolic derivatives and
thiophenolic compounds; (8) moderate oxidation of hydroquinones;
(9) oxidation of thiophenols; (10) oxidation of amino acids,
proteins and polyamides, primarily by attacking sulphide bonds.
These are cystine, methionone and tyrosine. Tryptophane also has
been shown to be reactive. ~eratin (which makes up the cyto-
skeletal structure in epithelial cells cytoplasm) and ClOz
13388~0
keratin sulfonic hydrosoluble acids; (11) carbohydrates are
altered at the CHO and CHzOH radicals to produce carboxylic
functions; and (12) Nitrates and sulphides are readily oxidized.
The chlorine dioxide described herein is of the type
referred to as stabilized chlorine dioxide. United States Patent
No. 3,271,242 describes a form of stabilized chlorine dioxide and
a method of making it which is particularly useful in carrying
out the present invention~ Further discussion of stabilized
chlorine dioxide in a form contemplated by the present invention
may be found in a treatise entitled Chlorine Dioxide by W. J.
Masschelein and published by the Ann Arbor Science Publishers,
Inc., copyright 1979 (note in particular pages 138-140). Various
embodiments of chlorine dioxide for various purposes are also
reviewed in this treatise.
The first step in the formation of plaque on a clean
tooth surface is the formation of acquired pellicle. Studies by
others have shown the following to be part of the acquired
pellicle formative process. Glycoproteins of salivary and other
mucous gland origin are attached to the hydroxyapatite crystals.
(Roukima, P.A. and Nieuw Amerongen, A.V., Sulphated Glycoproteins
in Human Saliva; Saliva and Dental Caries, (Sp. Supp.
Microbiology Abst.) 1979, p. 76. Embery, G., The role of anionic
glyco-conjugates, particularly Sulphated Glycoproteins in
relation to the Oral Cavity, Saliva and Dental Caries, (Supp.
Microbiol Abstr.), Information Retrieval 1978, pp 105-111).
Sulphated glycoproteins have a strong affinity to the calcium
1 ~38890
anion (ibid., pp 105-108). Most major salivary secreted
glycoproteins may be bound to certain ester sulphates (ibid).
These sulphated glycoproteins have been related to bacterial
agglutination or clumping (ibid., pp 108).
Clinical observations by the inventor have led to the
discovery that the process of acquired pellicle can be inhibited
by the use by humans of stabilized chlorine dioxide as a rinse.
Through such observations it has been learned that the chlorine
dioxide reacts with the sulphated glycoproteins to inhibit
pellicle formation. This process results primarily from, but is
not limited to, oxidation of the sulphide bonds. Since acquired
pellicle is the first step in plaque formation, this initial
inhibition alters the sequence of events to follow. The second
ætep, bacterial adhesion and subsequent steps are consequently
retarded. No disulphate enzymes capable of cleaning the sulphate
moieties of glycoproteins are known.
Bacterial agglutination includes the conversion of
sucrose to glucans and fructans by enzymes known as
glycosyltransferases. These enzymes are of bacterial origin.
The plaque mass becomes a complex extra cellular (of
microorganisms) matrix cont~;n;n~ sulphated glucosamineglycans,
proteoglycans, glycoproteins, sugar, proteins and lipids which
aid in the process of bacterial agglutination (Schluger, S.,
Yuodelis, R. and Page, R., Periodontal Disease, Chapter 6, pp
135-166, 1977, Lea & Febiger, Phila., Pa., Newbrun, E.,
Polyusaccharide Synthesis in Plaque; Microbiol Aspects of Dental
1338890
Caries, Vol. III, (Supp. Microbiology Abstr.), 1976, pp. 649-
66g). These compounds include the presence of sulphur and become
unstable in the presence of high oxygen compounds. The oxygen
splits the sulphide bonds to form sulphates or S02.
Clinical observations by the inventor have led to the
conclusion that all of these biochemical compounds are attacked
to a greater or lesser extent by stabilized chlorine dioxide.
Since thes- compounds may be used as nutrients for bacteria, the
reduction of the compounds will inhibit bacterial growth. More
specifically, the stabilized chlorine dioxide oxidizes
carbohydrates, proteins and lipids. Since these compounds arise
as bacterial byproducts and debris from dead and dying cells, are
of salivary origin and are the mechanism of agglutination of the
plaque mass, their degradation/oxidation retards plaque growth.
The initial bacterial residents of the plaque mass are
aerobic, oxygen using organisms. The saliva bathing the plaque
matrixes the source of oxygen. As the plaque thickens, the
deeper layers have a reduced oxygen content. The thicker the
aerobic population of plaque matrix, the lower the oxygen level
in the saliva. This permits the deeper layers of the plaque
matrix to develop an anaerobic population of bacteria (Globerman,
D.Y., and ~leinberg, I., Intra-Oral POz and Its Relation to
Bacterial Accumulation on the Oral Tissues; Saliva and Dental
Caries, (Sp., Supp. Microbiology Abstr.) 1976 pp. 275-292).
Clinical observations by the inventor lead to the
discovery that the use of stabilized chlorine dioxide as a mouth
- ~3~8~0
rinse will raise the level of oxygen in the saliva. The raised
level of oxygen within the plaque matrix will inhibit anaerobic
bacterial growth. As periodontitis is caused by anaerobic
bacteria, the potential for the development of periodontitis is
reduced by stabilized chlorine dioxide as a rinse.
The inhibition of acquired pellicle formation, the
prevention of bacterial agglutinization and the oxidization of
the plaque mass through rinsirg with chlorine dioxide in aqueous
solution are independent of the germicidal capacity of such
solution. Furthermore, these factors in combination with the
bacteriocidal capacity of chlorine dioxide in aqueous solution
renders the solution an effective pellicle and plaque inhibitor.
The permeability of sublinqual mucous tissue within the
mouth is increased substantially by exposure to hydrogen sulfide
(HzS) and methyl mercaptan (CH3SH). Gaffer and Rizzo papers
referenced in ~Effect of Hydrogen Sulfide and Methyl Mercaptan on
the Permeability of Oral Mucosa, J. Dent Res. 63(7), July, 1984,
pp 994-997). Accordingly, the toxic bacterial products attendant
plaque which produce these compounds have a related effect on
tissue permeabi~ity. Since chlorine dioxide breaks the di-
sulphide bonds of both these compounds, the use of chlorine
dioxide in aqueous solution as a mouthwash would reduce the
penetration potential of pathogenic materials. Evidence exists
that endotoxin and lipopolysaccharide from gram negative bacteria
are the worst of the products to penetrate the tissues.
1338390
Application of endotoxin to gingiva has caused gingival
inflammation (Ibid).
Chlorine dioxide in aqueous solution used in treatment
of plaque acts upon attendant gram negative bacteria. Thereby,
the inventor has learned though experimentation and observation
that chlorine dioxide can be a preventative product leading to
oral health.
~XAMPLE I
DEODORIZING MOUTHWASH
In an effort to find a suitable control agent for mouth
odor, attention was directed towards the use of chlorine dioxide.
The characteristics of stabilized chlorine dioxide which make it
especially useful is that it is antiseptic, a bactericide,
generally colorless, odorless, highly stable and has no apparent
detrimental or deleterious effect on humans at the concentrations
involved. As pointed out above, mouth malodor is primarily
caused by volatile sulfur compounds, such as hydrogen sulfide,
methylmercaptan and dimethyl mercaptan. As pointed out above,
these chemicals are produced as degradation products of
microorganisms acting on exogenous and endogenous proteinaceous
substrates, oral epithelium, food debris and saliva. In order to
control mouth odor, a deodorizing mouth wash consisting of a
solution of .02% chlorine dioxide in deionized water was utilized
as a rinse. Evidence indicates efficacy at lesser dilutions to
.005% with more rapid effect at dilutions to .2%. Sulfides are
- ~3~8~0
readily oxidized by chlorine dioxide. Bacteria implicated in the
production of malodor were also effectively controlled.
Inhibition of these microorganisms will reduce dental plaque
formation and maintenance process.
The chlorine dioxide mouthwash or rinse solution serves
to attack production and origin of malodor from the mouth by
splitting the sulfide bonds of both hydrogen sulfide and
methylmercaptan. Therefore, delivery of stabilized chlorine
dioxide provides reduction and elimination of these odors.
Further, the bacteriostatic, bactericidal, fungistatic and
fungicidal activity of stabilized chlorine dioxide will reduce
the number of microorganisms which assist in the production of
oral debris leading to disintegration of the organic compounds
ultimately producing hydrogen sulfide and methylmercaptan. The
known organisms include staphylococci, B. Subtilis, B.
Byrocaneous, Colon bacilli, Black Pigmented Bacteroides,
Clostridia, B. sporogenes, B. histolyticum and T. mucosum.
The mouthwash may be delivered s a simple rinse which
bathes the tongue. Literature indicates that over SO% of mouth
odor originates on the mouth and tongue surface, particularly the
posterior dorsal surface of the tongue. Accordingly, a rinse is
an effective treatment. However, persons with periodontal
involvement may have an increase in oral malodor from
disintegrated epithelial cells. A mouth rinse will not penetrate
to attack gingival crevicular odorizers. To optimize treatment
with a mouthwash containing stabilized chlorine dioxide, the wash
1~38890
must be delivered into the periodontal pockets as well as dorsal
and lingual surfaces of the tongue. The preferred treatment to
accomplish this is achieved by inserting the delivery tip of a
syringe into the pockets or gingival crevices or by administering
the wash by a mechanically powered water irrigating device such
as one of the type sold under the trademark "Water Pik",
manufactured by Teledyne Corp. Following irrigation, the user
can swish the wash throughout the mouth, covering the dorsal
surface of the tongue and other areas.
To improve the taste and appearance of the chlorine
dioxide solution, appropriate sweeteners and colorings such as
saccharin, peppermint and FTC #3 coloring agent may be added as
is common with commercially available mouthwashes and is well
known to those in the art.
EVALUATION OF NOul~ASH CONTAINING
CHLORINE DIOXIDE FOR ITS EFFECT ON
VOLATILE SULFUR COMPOUNDS
The test mouthwash which had a concentration of 0.05%
was dispersed in 3/8 oz. aliquots in individual plastic
containers. The study was performed over a three hour period on
six human subjects with objectionable early morning
concentrations of volatile sulfur compounds (VSC) greater than
0.5 ng CH3SH/10 ml mouth air.
Rinsing Procedure: Following initial early morning VSC
analysis on the day of evaluation, subjects were instructed to
12
1~38890
rinse, with vigorous swishing of rinse between teeth, for 30
seconds with 3/8 oz. volumes of the test mouthwash. After the
rinse was expectorated, the mouth was rinsed for 30 seconds with
15 ml of 18 megavolt pure water.
VSC Analysis: All VSC analysis were performed in
duplicate on each subject at the following times:
1. Initial screening to select subjects with
objectionable early morning concentrations of VSC.
2. On the day of evaluation, analysis were performed
on early morning mouth air samples before rinsing. These values
served as controls. Thus, each subject served as his own control
against which the effect of the rinse was calculated.
Immediately following these analysis, the subjects rinsed and
were re-analyzed, 3 minutes, 13 minutes, one hour, two hours and
three hours post rinsing. The results are summarized on the
following table:
o m 1 ~ O o
l. ~a890
~ O
+ t - ~ ~ u:>
CO ~ C~ ~D O
_~ ~ o ~~o ~r oo
o :~ . . . l.
o o o c o
r o
o~ . .
~ o oo o o o
~> o
C~
a~ . ... o
~co~o ~ o ~ o oo
_~ o
l~7 ~ ~ ~7 ~
z ~ ~ o o o o o o
E~ O
o ~ ~ ~ u~ ~ a
3 ~
~ c~ . . . . . .
~ m o o o o o o
Z:
~ ~ .n 1-- o ~1
O ~ ~ ~ o
O
n ~ o
:C
~ ~1
a ~
o o o o o o
~ ~. . . . . .
O ~c~ ~
t-- ~ a~ o s~
~. . a~
1:0 0 0 0 0 0
a~ _~ O
O~_ OCO ~ ~3
r
~O _IO_~ O ~ ~
S O
_I ~C~ O00 ~~O
O _IO O.1 _I O
.,1 ~
~3
O
~) ~ h
U~ OOOOO-~
14
'' '' 13~g890
The effectiveness of chlorine dioxide was tested both
in vivo and in vitro and demonstrated that stabilized chlorine
dioxide will kill at the 99% level in ten seconds streptococcus
mutans, the principle organism implicated in the etiology of
dental caries as well as other strains of organisms as
demonstrated by the following tests:
` 1338890
IN VITRO
BACTERICIDAL EFFECT OF C10z AGAINST STREPTOCOCCUS MUTANS
pH 200 ppm C102 SURVIVED
of Treatment
Medium Seconds Organisms/0.2ml No.Organisms %Kill
40,000 68 99.83
4.80 10 40,000 16 99.96
40,000 5 99.99
40,000 1336 99.66
5.95 10 40,000 98 99.76
40,000 101 99.75
29,600 *TNTC 0.0
5.01 10 29,600 125 99.58
29,600 70 99.76
29,600 *TNTC 0.0
6.06 10 29,600 *TNTC 0.0
29,600 122 99.59
9,400 744 92.10
5.06 10 9,400 176 98.10
9,400 44 99.50
9,400 1248 86.7
6.02 10 9,400 920 90.2
9,400 640 93.2
* Too numerous to count
16
- 133889U
THE BACTERICIDAL EFFECT OF Cl02
AGAINST BACTEROIDES GINGIVALIS
200 ppm Cl02 SURVIVED
pH ofTreatment Organisms/ No. %
MediumSeconds 0.2ml Organisms Kill
5.21 5 53 0 100%
53 0 100%
53 0 100%
______________ _ ___
5.96 5 53 0 100%
53 0 100%
53 0 100%
` ` 133~890
THE BACTERICIDAL EFFECT OF C10z AGAINST BACTEROIDES
NELANINOGENICUS
pH 200 ppm C10z SURVIVED
of Treatment
~edium Seconds Organisms/0.2ml No. Organisms % Rill
100,000 100,000 0
5.3 10 100,000 100,000 0
100,000 5,000 95
100,000 50,000 50
6.15 10 100,000 50,000 50
100,000 0 100
100,000 100,000 0
4.97 10 100,000 100,000 0
100,000 3,000 97
100,000 50,000 50
5.86 10 100,000 50,000 50
100,000 0 100
10,000 10,000 0
4.99 20 10,000 0 100
10,000 0 100
10,000 5,000 50
6.29 20 10,000 0 100
10,000 0 100
18
~3~890
THE BACTERICIDAL ~ C~l OF C102 AGAINST BACTEROIDES
MELANIOGENICUS
~continued)
pH 200 ppm ClO ~UKVl~V
of Treatment
Medium Seconds Or~anisms/p.2ml No.Organisms % Kill
10,000 10,000 0
4.97 20 10,000 0 100
10,000 0 100
10,000 3,000 70
5.85 20 10,000 0 100
10,000 0 100
8,560 *TNTC 0
4.97 10 8,560 312 96.3
8,560 67 99.2
8,560 *TNTC 0
5.87 10 8,560 2 99.9
8,560 1 99.9
*Too Numerous to Count
1338890
MATERIALS AND METHODS
Materials used in all experiments:
1.0 AC 5215 Odorid, C102 1000 ppm, Biocide Chemical Co.
Norman Ok
1.1 Chlorine-free distilled water employed throughout
1.2 Stirring apparatus, magnetic mixer with magnetic bar;
IEC Centrifuge 6000
1.3 Petri plates (12 x 50mm, 15 x 100mm).
1.4 HCl 0.1 N. NaOH p.1 N
1.5 Sodium thiosulfate solution 15%, employed 0.04 ml
1.6 Orthotolidine (o-toluidine) JT Baker, Baker Grde,
boiling point 200-200 C
C C H~ HN2, Standard Methods for Examination of
Water and Wastewater, 14th Ed. 1975 Neutral
Orthotolidine Regent, 0.04 ml employed
1.7 Diluent, saline with 0.5% Tween 80
Materials used in individual experiments:
1.0 Exp. Streptococcus mutans ATTC ~27152
1.1 Brain Heart Infusion Broth employed for initial culture
1.2 Plate counts performed on plate count agar.
2.0 Exp. Bacteroides gin~ivalis ATTC #33277
2.1 Anaerobic Tryptic Soy Agar (TSA) with 5% sheep blood
employed for initial isolation
2.2 Plate counts were performed on anaerobic TSA with 5%
horse serum
~L~3~89U
3.0 Exp. Bacteroides melaninogenicus ATCC #15930
3.1 Anaerobic TSA with %5 sheep blood was employed
throughout
3.2 Extended time interval for stirring of organisms was 30
seconds
4.0 Exp. Actinobacillus actinomycetuemocomitans ATCC #29522
4.1 Initial cultures prepared on chocolate agar
4.2 Plate counts were performed on anaerobic TSA without
sheep blood
Methods:
Initially each ATCC culture employed was grown on the
media documented under each organism. After isolation, all
cultures were maintained on appropriate media. The initial
bacterial count was determined by plating ten-fold serial
dilutions of the selected organism in its respective medium.
After incubation, the bacterial colonies were counted and 0.2 ml
of the selected dilution was employed against Cl02. ClOz was
employed at 200 ppm. 0.8 ml of CL02 was mixed with 0.2 ml of
organisms suspension and mao=mixed for the selected length of
time in seconds: 5, 10, 20 and 30. Two organism - ClOz mixtures
were mixed by a 45 tilting rotation in a small tube for the
selected period of time.
In each experiment, subsequent to each mixing time of
Cl02 was neutralized by the addition of 0.04 ml of sodium
1338890
thiosulfate. To assure complete neutralization of excess Cl02
has occurred, 0 04 orthotolidine was added to each ClOz -
organism-sodium thiosulfate mixture. If residual Cl02 is
neutralized, the mixture remains clear. If residual Cl02 is
present, the mixture turns yellow after the addition of
orthotolidine. Additional controls to determine the effect of
each reagent singly or in combination against each organism
include solidum thiosulfate-organism mixtures and sodium
thiosulfate orthotolidine organism mixt~res. A control plate
count without reagents was included for each organism.
All cultures except Streptococcus mutans were grown
anaerobically in CO at 37C for 48-96 hours. Streptococcus
mutans were grown aerobically at 37C for 48 hours.
IN VIVO CHLORINE DIOXIDE EVALUATION
Thirty-nine periodontal pockets in twenty-nine
patients were examined by dark field and phase microscopy. The
motility and density of bacteria were evaluated from zero to
three with zero being no activity and three very active.
Of the thirty-nine teeth, thirty were molars, three
were bicuspids and six were in the anterior region. Pocket depth
ranged from 4 to 12 millimeters.
The patients were instructed to use a 0.1% chlorine
dioxide solution twice daily. Four of the patients used chlorine
1338~90
dioxide as a mouth rinse and twenty-five used it as an irrigant
with monoject 412 twelve cc syringe.
The findings follow:
I~38890
CLINICAL EFFECT OF .1% CHLORINE DIOXIDE
BEFORE BEFORE
SUR- BEFORE AFTER % DARR DARR %
TOOTH t CODE t FACE PHASE PHASE C~ANGE FIELD FIELD CHANGE
14 001 N 2 0100% 3 1+50%
23 001 D + 0100% 2 + 75%
002 D 0 0 0~ 1 0100%
18 003 D 2 0100% 2+ 1- 70%
004 L + 0100% + + 0%
18 004 D 2 0100% 2+ 1 60%
14 005 M 2 1 50% 2 2 0%
005 L 1 0100% 2 0100%
006 L 0 0 0% 2 0100%
19 007 D 0 0 0% 3 0100%
31 008 B 2 0100% 2+ 0100%
7 009 D 3 0100% 3 2 33%
2 010 M 1 0100% 2 0100%
4 011 M 0 0 0% 2 0100%
011 D 1 0100~ 3 1- 75%
3 012 M 2 1- 63% 3 2 33%
14 012 M 2 1 50% 3 2 33%
18 013 M 0 0 0% 3 1 67%
3 014 M 0 0 0% 1 0100%
2 015 M 2 1 50% 3 2 33%
2 015 D 2 + 75% 3 + 83%
21 016 D 0 0 0% 2+ 0100%
14 017 N 1 0100% 3 2 33%
3 018 M 1 0100% 1 0100%
32 019 D 1+ 0100% 2 0100%
31 020 B 2 + 75% 3 + 83%
2 021 M 2+ 1 60% 3 2 33%
32 022 D 1 0100% 1 + 50%
24
- 1~38890
CLINICAL EFFECT OF .1% C~LORINE DIOXIDE
(continued)
BEFORE AFTER
BEFORE AFTER % DARK DARK %
TOOT~ t CODE ~ SURFACE PHASE PHASE CUANGE FIELD FIELD CHANGE
31 023 M l 0 100% 3 0100%
3 024 D 2 0 100% 2 0100S
025 D 2 0 100% 3 1 67%
26 025 D 0 0 0% 3 1 67%
4 026 M 2 0 100% 2+ 1- 70%
12 026 M 1 + 50% 3 + 83%
8 027 B 1 0 100% 2 1 50%
3 028 M 1 0 100% 3 1 67%
31 029 M 1 + 50% 3 1+50%
11 030 D + 0 100% 1 + 50S
13388gO
EVALUATION DATA
Phase
(Thirty Pockets with Activity)
Number of Pockets% Resolution% of Total
21 100% 70%
2 75% 6.67%
1 63% 3.33%
1 60% 3.33%
50% 16.07%
Mean resolution
(All bacterial activity stopped or was reduced)
Dark Field
(Thirty-nine Pockets with Activity)
Number of Pockets% Resolution% of Total
14 100% 35.89%
3 83% 7.69%
2 75% 5.13%
2 70% 5.13%
4 67% 10.26%
1 60% 2.56%
50% 12.82%
6 33% 15.38%
(Two of the pockets exhibited no reduction in bacteria after the
use of chlorine dioxide)
26
-
13~38830
EXAMPLE II
TOOTHPASTE
As demonstrated above, stabilized chlorine dioxide can
be an effective agent on odor producing microorganisms and
enzymes. However, the effectiveness of chlorine dioxide can be
enhanced when included as an ingredient of a toothpaste.
Toothpaste is more effective than a rinse for removing malodor
from the gums or gingiva. The action of the brush dislodges dead
cells and putrescent debris from the gingival crevices as well as
on the various mouth surfaces and on the tongue. The chlorine
dioxide contained in the toothpaste acts as discussed above to
prevent malodor and serve as a deodorizer by attacking hydrogen
sulfide and methylmercaptan. A typical toothpaste would have the
following composition: stabilized chlorine dioxide approximately
.005% to .2%; detergent polishing agent; calcium carbonate or
silica gel; flavoring, saccharin; peppermint; coloring agent.
These other ingredients may vary and are the basic ingredients in
many toothpastes as is well known to those in the art. Other
formulations including chlorine dioxide as the active ingredient
would work as well.
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EXAMPLE III
ANTI-PLAQUE AGENT
Dental plaque, as mentioned above, is formed by a
combination of actions begi nni ng with acquired pellicle from
saliva coating the tooth and a subsequent adhesion to the coating
by streptococcus organisms. S. Mutans degrade sucrose into
glucose or fructose which are then compounded into dextrans and
levans. The dextrans act as a nutrient substrate for the growth
of additional organisms and the production of acids which
demineralize tooth enamel and dentin causing tooth decay. The
stabilized chlorine dioxide reacts with sulphated glycoproteins
to inhibit or reduce pellicle formation through oxidation of the
sulphide bonds. Streptococcus sanguis more frequently than
streptococcus mutans will adhere to pellicle to provide dextrans
by way of glucocyltransferases. Chlorine dioxide is lethal to
streptococcus mutans in vitro and materially reduces their
numbers in vivo. The reduction of motility and mytosis by
chlorine dioxide will reduce the amount of plaque formation.
Dental plaque formation subsequent to any acquired pellicle is
reduced when the microbial content of the mouth is reduced. Thus
chlorine dioxide is an effective anti-microbial agent which
functions as a dental plaque inhibitor or retardant and as an
anti-cariogenic agent. Preferred concentrations are in the range
from .005% to .2% in aqueous solutions as for example, in
deionized water with suitable coloring and flavorings for patient
comfort.
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EXAMPLE IV
ANTI-GINGIVITIS, ANTI-PERIODONTITIS AND
GINGIVAL BLEEDING PREVENTATIVE
Gingivitis and the various forms of periodontitis are
known to be caused by bacteria. Principal forms implicated are
Black Pigmented Bacteroides and Actinobacillus
Actinomycetumcomitans. Gingivitis occurs from toxins produced by
the aerobic bacteria in coronal dental plaque and periodontitis
occurs from toY; nC produced by anaerobic bacteria in infection
extending into periodontal pockets or spaced between the gingiva
(gums) and the tooth root. Thus, control of gingivitis is by
oxidation of compounds produced as bacterial by products that
otherwise would be the mechanism of agglutination of the plaque
mass in the coronal dental plaque and control of periodontitis by
raising the level of oxygen in the saliva to raise the level of
oxygen in the plaque matrix and inhibit anaerobic bacterial
growth in the plaque matrix found in the gingival crevices and
elsewhere.
By the use of an oxidizing agent of the strength of
chlorine dioxide in the mouth, it will increase the amount of
aerobic bacterial population which will prevent the accumulations
of anaerobic populations in the higher oxygen tension. Since the
anaerobes stimulate the immune reaction, which include lymphocyte
cloning and subsequent release of the compliment cascade to
induce inflammation and bone loss, the chlorine dioxide will help
prevent periodontitis through its higher oxygen tension created
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in the saliva. Further in this particular application, the
higher oxygen tension will provide more oxygen available to
convert the adjacent tissues from anaerobic into aerobic
glycolysis. This will increase the number of
adenosinetriphosphate molecules to increase the energy available
for adjacent cells. The covering epithelial cells are the source
of intracellular cementing glycoproteins and proteoglycans. If
the cells do not have enough oxygen to function in aerobic
glycolysis, there will be 1/18 the ATP production and with it the
interference of active transport (delivery of nutrition to the
cells) as well as cell adhesion to hold an effective covering and
minimize bacterial penetration into the underlying connective
tissues.
Clinical evidence had documented improvement in
treatment of the above diseases when stabilized chlorine dioxide
is used. The organisms currently implicated in the above are
listed as follows:
1. Gingivitis
Actinomyces forms including Actinomyces
Israeli
Coccus forms
2. Acute Necrotizing Ulcerative Gingivitis
Spirochetes
Bacteroides Intermedius
Fusiform Nucleatum
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3. Juvenile Periodontitis
Actinobacillus Actinomycetumcomitans
Capnocytophagia
Bacteroides Intermedius
4. Adult periodontitis
Bacteroides Gingivalis
Bacteroides Intermedius
Actinobacillus Actinomycetumcomitans
Vibro Nucleatum
Fusobactium Nucleatum
Fusobactium Bacteroides
Anaerobic Cocci
Research has demonstrated that stabilized chlorine
dioxide is lethal to Bacteroides gingivalis and Actinobacillus
Actinomycetumcomitans in vitro at the 95% level in twenty seconds
with a .02% concentration. Research in vivo demonstrates that
these organisms are significantly reduced or eliminated in humans
when chlorine dioxide agent is applied to the pocket area using a
syringe or water injection device with a needle to force
penetration into the gingival crevices with the chlorine dioxide
concentration in the range of .05% to .2%. Both gingivitis and
periodontitis cause an increase in the rate of epithelial cells
sloughing, aggravate oral malodor and cause some ulceration of
tissue leaving the gingival bleeding; such bleeding is also
reduced by treatment with a solution of stabilized chlorine
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dioxide through splitting of the di-sulphide bonds of hydrogen
sulphide and methyl mercaptan.
Stabilized chlorine dioxide in aqueous solution is thus
highly useful in the treatment of gingivitis, periodontitis and
bleeding gingiva.
BXAMPLE V
DENTURE SOAR
The malodors of the mouth result substantially from the
volatile sulfur compounds which are present in saliva. Saliva
coats and penetrates dental prosthetic devices including full
dentures and partial dentures and forms an acquired pellicle.
Further, food and other cellular debris adheres to dental
prosthesis. Both anaerobic and aerobic bacteria accumulates on
and in the microscopic faults and pores of these prosthetic
devices and form a plaque matrix, as discussed above. Stabilized
chlorine dioxide in aqueous solution has been demonstrated as a
bactericide. It is also effective for neutralizing sulfur-based
malodors, removing organic debris from dental prosthesis and as a
disinfectant. As a dental soak the solution is antimicrobial,
removes sulfur compounds and breaks down organic material and can
be used in solution form having a concentration of from
approximately .002% to .27%.
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EXAMPLE VI
CELLULAR DEBRIDEMENT AGENT
Many wounds and desquamative diseases such as Lichen
Planus, Desquamative Gingivitis and desquamative dermatological
disease are aided by organic debridement agents and antimicrobial
agents. Solution or composition contA; n; ng stabilized chlorine
dioxide in aqueous solution in .05% to .1% and higher
concentrations is effective to treat these problems. One
particular application would be in veterinarian applications and
for the purpose of reducing odor attendant to these wounds and
diseases.
EXAMPLE VII
SANITIZER AND COLD STERILIZATION AGENT
The known bacterial, fungicidal and viralcidal
characteristics of chlorine dioxide also make it extremely useful
as a sanitizer which can be a solution in which materials can be
dipped or by application in an aerosol spray. The sanitizer can
be used for food, sickroom use, bathroom and cold sterilization
of many instruments and pieces of equipment not generally
amenable to autoclave sterilization. Again, the concentration of
the stabilized chlorine dioxide would be preferably in the range
of from .005% to 2.0%.
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EXAMPLE VI I I
CONTACT LENS SOA~C
Contact lenses accumulate bacteria and cellular debris
from the eye. The known bactericidal, fungicidal and viralcidal
capacity of stabilized chlorine dioxide along with its low
toxicity makes stabilized chlorine dioxide solution an ideal lens
soak. In addition, the capacity to degrade organic debris helps
keep the lens clean and nonirritating. The preferred range of
concentration is .005% to .2% in sterilized water.
It will be seen from the foregoing that stabilized
chlorine dioxide in solution or as part of composition or
compound is effective in treating and preventing the formation of
mouth malodor, inhibiting acquired pellicle and as a suitable
plaque control agent, a bactericide, viralcide and fungicide
superior to other compositions used today. Stabilized chlorine
dioxide has been used for many years in other areas and extensive
study in animals and in man have demonstrated its low toxicity
and safety. Chlorine dioxide is approved by the Environmental
Protection Agency for water purification, food preparation and
preservation as well as bacteriostatic, fungistatic and
viralstatic agent.
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