Drug – bio-affecting and body treating compositions – Dentifrices
Reexamination Certificate
2000-02-17
2002-07-23
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Dentifrices
C424S048000, C424S053000, C424S401000, C424S614000, C514S900000, C514S901000, C514S902000, C514S494000
Reexamination Certificate
active
06423300
ABSTRACT:
FIELD OF INVENTION
The present invention provides oral compositions comprising a zinc compound containing free available zinc and at least one stabilized or stable E
h
raising compound distributed in an oral vehicle. The present invention is further directed to a method of inhibiting the formation of anionic sulfur species in the oral cavity and preventing a lowering of the E
h
of the oral cavity. A method of simultaneously reducing oral malodor, gingivitis and periodontitis by preventing or reducing oral putrefaction is also provided by this invention.
BACKGROUND OF THE INVENTION
The hard and soft tissues of the mouth are covered with microbial populations that contain bacteria with different metabolic capabilities. The Gram-positive bacteria within these microbial populations readily catabolize carbohydrates to produce acids which attack the hard tissues of the oral cavity, resulting in the formation of dental caries lesions (cavities). In contrast, the Gram-negative bacteria, especially the anaerobes readily metabolize various amino acids contained in salivary (and to lesser extent other) peptides and proteins in the oral cavity to form end-products which favor the formation of oral malodor and periodontitis. This process of peptide, protein and amino acid degradation by the mouth bacteria is referred to as oral bacterial putrefaction. The mixture of malodorous compounds produced by the Gram-negative anaerobic bacteria during putrefactive degradation of proteins, peptides and amino acids include hydrogen sulfide, methyl mercaptan, and dimethyl sulfide (formed from the sulfur containing amino acids cysteine, cystine and methionine); indole and skatole (formed during the metabolism of tryptophan); cadaverine and putrescine (produced from lysine and ornithine); and butyrate and valerate (produced from the metabolism of other amino acids). The production of these malodorous compounds in the oral cavity results in a condition commonly referred to as oral malodor.
Hydrogen sulfide, methyl mercaptan, butyrate and propionate are putrefaction end-products that also have cell and tissue altering non-inflammatory roles in the periodontitis process. Hydrogen sulfide and methylmercaptan are compounds particularly effective in facilitating the oral epithelium penetrability of toxins and other large molecular weight compounds produced by Gram-negative bacteria, and leading to the inflammation and tissue degradation characteristics of gingivitis and periodontitis. Gingivitis is a condition in which the gingiva is red, swollen and bleeding. If left untreated, gingivitis may develop into periodontitis, a condition characterized by destruction of the periodontium, including epithelial attachment loss, periodontal membrane and ligament destruction, and loss of gingiva and alveolar bone. Severe periodontitis resulting in deep periodontal pockets may ultimately result in tooth loss.
Previous studies have largely focused on the use of germicidal agents to treat gingivitis-periodontitis and oral malodor. Until the findings by the present invention, previous studies have not recognized that gingivitis-periodontitis and oral malodor arise from a common process, oral bacterial putrefaction; also that this putrefaction can be inhibited by simultaneously lowering the ability of the oral bacteria to reduce the oxidation-reduction potential (E
h
) of the oral cavity and at the same time, raising the existing E
h
to where the oral environmental E
h
is not conducive to oral putrefaction and oral disease production.
The metabolism and growth of anaerobic bacteria in the oral cavity is favored when the E
h
. is lowered. The present invention has discovered that the oxidation-reduction potential (E
h
) is a key regulating factor in oral bacterial putrefaction. The lowering of the E
h
of the oral cavity has been found to occur in two steps, a depletion of oxygen followed by the generation of electron rich compounds. The present invention has discovered from studies on the isolation and catabolism by the oral bacteria of nitrogenous substrates in human saliva that the primary compounds responsible for lowering the E
h
of the oral cavity are non-volatile sulfur containing anions derived largely from cysteine and cystine (Table 1). These include the anionic sulfur species, sulfide (S
=
), hydrogen sulfide (HS
−
) and methyl mercaptan (CH
3
S
−
). Such anions favor an ecological environment of reduction (lower E
h
) that enables the Gram-negative anaerobic bacteria in the mouth to grow, engage in oral putrefaction and produce electron-rich compounds leading to and maintaining a prolonged lowering of the E
h
of the oral cavity and the undesirable conditions of oral malodor, gingivitis and periodontitis. A lower E
h
favors the oral bacterial putrefaction process whereas a higher E
h
is inhibitory.
TABLE 1
Lowest E
h
reached with the common amino acids when
incubated with the mixed bacteria in salivary sediment.
E
h
(millivolts)
amino acids
Group A
Group B
Group C
alanine
100
arginine
25
asparagine
70
aspartic
80
cysteine
20
cystine
−10
glutamic
30
glutamine
100
histidine
70
isoleucine
115
leucine
110
lysine
95
methionine
20
ornithine
55
phenylalanine
100
proline
100
serine
115
threonine
110
tryptophan
85
tyrosine
40
valine
105
salivary supernatant −25; water control 142
The present invention provides compounds that simultaneously (i) inhibit the formation of these electron-rich compounds and thereby prevent the E
h
from falling to harmful levels and (ii) react with any electron-rich compounds formed and by thus neutralizing them, raise the E
h
to safer levels. It has been surprisingly discovered in accordance with the present invention that an oral composition containing a zinc compound capable of providing free available zinc and a stabilized or stable E
h
raising compound can effectively prevent the lowering of the E
h
. This is crucial to preventing oral bacterial putrefaction, the metabolic process that is the basis and that results in the development of both oral malodor and gingivitis-periodontitis.
Zinc compounds, hydrogen peroxide, and chlorine dioxide have each been used as therapeutic agents in oral compositions to destroy harmful bacteria involved in oral malodor and gingivitis-periodontitis formation. Previous studies where zinc has been identified as having anti-microbial and anti-plaque effects have made no distinction between zinc compounds where the zinc is freely available and where it is not. (See for example, U.S. Pat. No. 4,289,755 to Dhabhar). The zinc species is an important element of this invention, since free available zinc (zinc ion) within the oral cavity is required to inhibit the E
h
lowering capability of a pathogenic, putrefactive microbiota. Zinc compounds used in the compositions previously described include compounds where zinc is not freely available. Zinc that is bound or complexed to various ligands and zinc species that have a low solubility and form precipitates are prevented from reacting with the E
h
lowering enzymes and products produced by the putrefactive microbiota and hence are poorly suited for the purposes of this invention.
The solubility for zinc compounds vary as shown in the table below.
Solubility of selected zinc compounds
Solubility
Compound
Formula
(g/100 cc)
zinc chloride
ZnCl
2
432 @ 25° C.
zinc citrate
Zn
3
(C
6
H
5
O
7
)
2
slightly soluble
zinc acetate
Zn(C
2
H
3
O
3
)
2
30 @ 20° C
zinc lactate
Zn(C
3
H
5
O
3
)
2
5.7 @ 15° C.
zinc salicylate
Zn(C
7
H
5
O
3
)
2
5 @ 20° C.
zinc sulfate
ZnSO
4
soluble
zinc oxide
ZnO
0.00016 @ 29° C.
zinc nitrate
ZnNO
3
)
2
infinitely soluble
Data are from the
Handbook of Chemistry and Physics
, Chemical Rubber Company, 67th Edition CRC Press, Boca Raton, Fla., 1986-87.
It is evident from this table that the amount of zinc that will be soluble and available in the oral cavity for controlling pathogenic microbiota will vary considerably. Those zinc compounds that provide low levels of zinc ion in solution, such as zinc oxide, are unsuitable for
Codipilly Milroy
Kleinberg Israel
Jagoe Donna
Krass Frederick
The Research Foundation of State University of New York
LandOfFree
Compositions to control oral microbial oxidation-reduction... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions to control oral microbial oxidation-reduction..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions to control oral microbial oxidation-reduction... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2907192