Drug – bio-affecting and body treating compositions – Dentifrices – Plant extract of undetermined constitution
Reexamination Certificate
2000-10-24
2004-11-09
Tate, Christopher R. (Department: 1651)
Drug, bio-affecting and body treating compositions
Dentifrices
Plant extract of undetermined constitution
C424S049000, C424S729000, C424S732000, C424S766000
Reexamination Certificate
active
06814958
ABSTRACT:
TECHNICAL FIELD
The present invention relates to food compositions, oral compositions and pharmaceutical compositions for preventing or treating periodontosis and methods for preventing or treating periodontosis by using these compositions.
BACKGROUND ART
Matrix metalloprotease (hereinafter referred to as “MMPs”) is a generic name of extracellular matrix protease which are characterized by having zinc (II) ion at their active sites. The metabolism of this extracellular matrix is adjusted mainly by the balance between the MMPs and metalloprotease inhibitors (TIMP) which is specific for MMPs and is derived from organizations. It is known that periodontosis such as the periodontitis is associated with the structural anomaly of the extracellular matrix components and the loss of metabolism balance such as synthesis and degradation of the extracellular matrix component resulting from the abnormal expression of MMPs.
More than 10 enzyme molecules are know as MMPs, including collagenase (MMP-1 and 8), stromelysin (MMP-3), gelatinase (MMP-2 and 9) and the like (Yoshihara, Niina: Inflammation and Immunity, 2, 177-185, 1994). These are produced by various kinds of cells.
In periodontosis such as gingivitis and periodontitis, MMPs seems to be deeply concerned in development and progress of periodontosis. It is suggested that MMPs concerning the organization destruction of gingivitis, periodontitis and like periodontosis are collagenase and gelatinase mainly produced by human gingival epithelium cells, gingiva fibroblasts and periodontal membrane cells. More specifically, it is thought as follows: periodontosises such as gingivitis and periodontitis are caused by the infection of periodontium with specific periodontosis original fungus (
P. gingivalis
). MMPs are produced by epithelial cells, gingiva fibroblasts and periodontal membrane cells in the periodontium which have received external stimulation by the pathogenic fungi. As the result, a periodontal membrane structure which connects teeth and periodontium is destroyed in cell-derived MMPs. Mainly by this destruction, the periodontosis occurs and develops (M. Kylmaniemi et al: J. Dent Res., 75:919-926, 1996). It is also suggested that the activity of the MMPs derived from periodontium is easily increased by one's smoking habit, development of diabetes and other factors which change the immune responsiveness of organisms, leading to the increased rate of the development and progress of gingivitis, periodontitis and like periodontosis.
Therefore, it is considered that the inhibitor of MMPs is effective for treatment and prevention of periodontosis such as periodontitis and gingivitis and the like. For example, there is a report on the use of tetracycline and its modification, which reportedly inhibit the MMPs derived from gingiva fibroblasts and epithelial cells, in the treatment of periodontitis (L. H. Nip et al: J. Periodont Res., 28: 379-385, 1993).
However, tetracycline-based antibiotics, which are synthetic substances, have particular side effects and risks of resistant microbe appearance in the human body. Considering this fact, it is not desirable that these antibiotics are taken in the long term for treating or preventing periodontosis such as periodontitis. Therefore, the desired MMPs inhibitor is of natural origin and has few side effect by taking the inhibitor, and has inhibitory effects on the MMPs derived from periodontium. Moreover, sufficient inhibitory effects on MMPs must be demonstrated at a normal and appropriate dose.
As the MMPs inhibitors of natural origin, for example, flavones or anthocyanidins of natural origin reportedly has the MMPs inhibitory effects (Japanese Unexamined Patent Publication No. 1996-104628). Reported inhibitors of natural origin on one kind of the MMPs, collagenase, include schizonepeta herb extract, mint extract (Japanese Unexamined Patent Publication No. 1994-183990), nordihydroguaiaretic acid (Japanese Unexamined Patent Publication No. 1992-217626) and polyporenic acid C (Japanese Unexamined Patent Publication No. 1997-40552). In addition, tetracyclic triterpene 20-carboxy-16-hydroxy-21-nor-5 &agr;-7,9(11)-lanostadien-3,24-dione which is extracted from
Daedalea dickiusi
and refined is also reported to have an inhibitory effect on collagenase (No. 1997-235293).
M. Makimura et al reported in J. Periodontol., 64(7):630-636, 1993 that catechins contained in tea showed the inhibitory effects on collagenase derived from prokaryotic and eukaryotic cells and on collagenase derived from gingival crevicular effusion of periodontosis patients.
Furthermore, Japanese Examined Patent Publication No. 1992-27204 reported the preventive effects of polyphenol extracted from green tea on dental caries and periodontosis.
A supplementary food product (trade name: Body Language, Oxyfresh Co., U.S.A.) appealing its anti-inflammatory effect on the gingiva is commercially available in the U.S.A. This supplementary food contains a grape seed extract which reportedly exhibits the inhibitory effect on some of the collagenase derived from fungus (L. Robert et al: Path. Biol, 38:608,1990) and coenzymes Q10.
Meanwhile, focusing on antioxidant effects, Japanese Unexamined Patent Publication No. 1995-196534 reports the synergistic antioxidant effect of the activity of the combination of hydrophilic polyphenol having the structure similar to that of catechin or flavonolignan (e.g., proanthocyanidin) and lipophilic carotenoid or lipophilic procarotenoid (e.g., vitamin E).
DISCLOSURE OF INVENTION
An object of the present invention is to provide a composition effective in preventing or treating periodontosis, particularly effective in preventing and treating periodontosis aggravated by smoking, particularly a food composition, oral composition and pharmaceutical composition.
The inventors of the present invention conducted extensive research and found the following: the MMPs inhibitory effect is increased by using an extract containing natural polyphenol in combination with at least one of vitamin C (and its salts), vitamin E, vitamin A and beta-carotene. They also found that excellent periodontosis preventive or therapeutic effect can be achieved by the composition containing these extract and vitamins. The present invention was accomplished based on these findings.
Additionally, it was found that the addition of a plant extract having an antibacterial activity to the above composition which comprises the extract containing the natural polyphenol and vitamins can remove the stimulation for the periodontium of the periodontosis original fungus, whereby the preventive effect or therapeutic effect can be increased.
Moreover, the inventors of the present invention found that the combined use of the extract containing the natural polyphenol and the above vitamins in the presence of nicotine can further improve the inhibitory effect on the increase in MMPs concentration. Nicotine is a main stimulant found in cigarette smoke. The results of in vitro test reveal that the stimulation of nicotine produces adverse effects such as inhibition of periodontium cell proliferation, increased production of collagenase and the like. Accordingly, smokers tend to contract periodontosis and suffer fast progress of the same induced by smoking. Even a passive smoker, that is, a person who is under the environment where nicotine exists, such as the spouse of a smoker, tends to contract periodontosis and suffer fast progress of the same as well as the smokers. Based on the above, the inventors of the present invention found that the increase in the MMPs concentration in the oral cavity induced by smoking can be effectively inhibited by the composition which comprises the extract containing the natural polyphenol and the above vitamins.
The present invention provides the inventions listed below:
Item 1. A composition for preventing or treating periodontosis comprising (A) at least one member selected from extracts containing natural polyphenol and (B) at least one member selected from the group consisting of vitamin C or its salts, vitamin E,
Sughrue & Mion, PLLC
Sunstar Inc.
Tate Christopher R.
Winston Randall
LandOfFree
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