JPH0441417A - Composition for oral cavity - Google Patents

Abstract

PURPOSE:To obtain a composition for the oral cavity, containing k-casein, having an inhibitory activity against collagenase derived from humans and useful for preventing and treating periodontosis. CONSTITUTION:A composition for the oral cavity containing k-casein. The k-casein is obtained by adding bivalent cations to a solution of an alkali metal salt of milk casein (at 0.5-6.0 wt.% concentration expressed in terms of proteins and pH 7-10) normally prepared from cattle, goat and sheep milk according to a conventional method while cooling the milk to 0-15 deg.C. The aforementioned ingredient is contained in an amount of normally 0.001-10 wt.%, preferably 0.01-5.0 wt.% in the composition for the oral cavity. Since the above-mentioned ingredient is one ingredient of milk proteins, safety for use is extremely high without regard to the amount thereof blended.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention provides an oral composition containing Ni-casein, more specifically, a composition for preventing periodontal disease containing Ni-casein and having human-derived collagenase inhibitory activity. The present invention relates to therapeutically useful oral compositions.

[Conventional technology]

Periodontal disease is a general term for inflammatory diseases that include various pathologies in the periodontal tissue, but there are two main types: gingivitis, where inflammation is generally limited to the gingival region, and periodontitis, where inflammation reaches the alveolar bone and becomes chronic. Separated. Periodontitis used to be called alveolar pyorrhea, but as it becomes chronic, it causes destruction of the gingiva and alveolar bone, leading to tooth loss.Periodontitis accounts for 5% of tooth loss, and it is common among middle-aged and elderly people. Approximately 80% of people are affected.

Periodontal disease is caused by a specific group of bacteria in the plaque in periodontal pockets, especially the black pigment-producing batataeroides (
Bacteroides) pathogenic theory is considered to be the most likely (for example, Journal of C11nical
Periodontology, Volume 13, 91
(see p. 2, 1986), and its periodontal tissue destructive action is thought to involve direct acting factors (such as enzymes and endotoxins) and indirect acting factors (mediated by host immune responses) derived from bacteria. However, in either case, the common point is that the collagen in the gums and alveolar bone is degraded and absorbed (American Journal of
Pathology, 92 t”, 509 pages,
(see 1978).

Collagenase derived from batatteroides and gingival fibroblasts are attracting attention as collagenases associated with periodontal disease. The former has recently been partially purified and is a rare enzyme that requires metals and thiols at the same time, but there are still many unknown points (Journal of Pe
Riodontal Research, Volume 23.

258, 1988). On the other hand, fibroblast-derived interstitial collagenase (hereinafter referred to as collagenase unless otherwise specified) has been elucidated in detail and its primary structure has been clarified (The Journal of Biologic
al Chemistry, Vol. 261, p. 6600, 1986). Collagenase is a rate-limiting enzyme in degrading interstitial collagen (type I, type ■, and type ■ collagen) in connective tissue, and plays an important role in collagen metabolism. Collagenase activity increases in inflamed gingiva (Journal of P
Eriodontal Research, Volume 16, Page 417.

1981) and that collagen is reduced from the early stages of gingivitis (Archieves of
0r-al Biology, vol. 18, p. 899,
(1973), it is thought that gingival collagenase is deeply involved in the progression of periodontal disease. Conventionally,
To prevent and treat periodontal disease, removal of plaque and tartar from periodontal pockets through scaling and root planing,
Removal of periodontal pockets (gingivectomy) was used.

In addition, a therapeutic agent containing the antibacterial minocytalin has recently been developed as a drug therapy.

It has been reported that minocycline has not only antibacterial activity but also the activity of inhibiting collagenase derived from Bacteroides and neutrophils in vitro (Journal
of the Japanese As5ociat
ion of Periodontology, 30
Vol. 182, 1988).

[Problem to be solved by the invention]

The above-mentioned known methods include physical therapy according to a doctor's instructions.

Treatment may be based on surgical or drug therapy.

However, considering that periodontal disease is a common disease with a high incidence rate, and that the condition tends to worsen before it is treated by a doctor, it is important to consider It is desirable to use highly safe food-derived materials for oral materials such as mouthwashes that eliminate the aforementioned pathogenic factors and are useful for the prevention and treatment of periodontal disease.

An object of the present invention is to provide a highly safe food material that is effective in preventing and improving periodontal disease.

[Means to solve the problem]

The present inventors found that among the above-mentioned causes of periodontal disease, inhibiting the activity of collagenase, which plays an important role in controlling the decomposition and absorption of gingival and alveolar bone collagen, is effective in preventing and improving periodontal disease. Focusing on a certain point, as a result of repeated research in search of collagenase inhibitors from a wide range of food-derived materials, we discovered that casein, a component of milk protein, has strong collagenase inhibitory activity, and completed the present invention. I ended up letting it happen.

The present invention relates to an oral composition characterized by containing casein.

Casein is a type of protein contained in milk, and is a phosphoprotein that is precipitated by adding acid to skim milk at 20° C. and adjusting the pH to 4.6.

Raw casein consists of two components, α- and β-casein, due to differences in electrophoretic mobility, and among these, α-casein is further composed of two components, αS- and Ni-casein (αS-casein is not present in human milk). ,).

Ni-casein contains 0.4 MCa of α-casein components.
CJ! It corresponds to the component soluble at pH 7, 0, 4℃,
In milk, it accounts for 13% by weight of total casein.

The method for producing casein used in the present invention is not particularly limited, and any commonly used method may be used. For example, a milk casein alkali metal salt solution obtained from cow, goat, or sheep milk by a conventional method (protein concentration: 0.
It can be obtained as a soluble fraction by adding divalent cations to 5-6.0% by weight, pH 7-10) under cooling at 0-15°C. Insoluble casein containing αS-casein as a main component is removed by precipitation, and casein is separated from the soluble fraction to obtain casein rich in casein.

When casein obtained by such a method is used in the oral composition of the present invention, commonly used known components can be optionally added depending on the type of composition.

Such oral compositions may be in the form of liquids, solids, or semi-solids, and preferred compositions include foods such as chewing gum, candy, drinks, toothpaste, cleaning agents, and troches. Examples include autopsy, liquid application, etc.

The excipients or auxiliary agents used to produce these oral compositions may be appropriately selected from those commonly used for the same purpose depending on the shape, and are not particularly limited. , such as lactose, starch, cornstarch, magnesium stearate, sorbitol, mannitol, carboxymethylcellulose, hydroxypropylcellulose.

Hydroxypropyl methylcellulose, saccharin,
Sodium lauryl sulfate, sodium lauroyl sarcosine, glycerin, polyethylene glycol, polyvinyl alcohol, carrageenan.

Gum arabic, gelatin, ethanol, menthol, fatty acids, citric acid, silicic anhydride, calcium diphosphate,
Hydroxyapatite, calcium carbonate, titanium dioxide, etc. are preferably used.

Sweeteners commonly used in foods are added to the above composition.

Colorants, fragrances, preservatives, etc. can be used as appropriate, and disinfectants such as chlorhexidine, antibiotics such as ampicillin, anti-inflammatory agents such as lysozyme, and hemostatic agents such as tranexamic acid are combined to prevent periodontal disease. It is also possible to enhance the improvement effect.

The collagenase inhibitory effect of casein in the present invention is unique, and αS, which is the main component of milk protein, is unique.
- and β-casein have no such effect.

The amount of casein in the oral composition useful for the prevention and treatment of periodontal disease produced in this way varies depending on the dosage form, but is usually 0.001 to 10% by weight, preferably 0.01% by weight. It is desirable that the amount is 5.0% by weight.

〔Effect of the invention〕

The oral composition according to the present invention has excellent inhibitory activity against collagenase, which is the cause of collagen absorption in the gingiva and alveolar bone in periodontal disease, by incorporating casein, and has excellent inhibitory activity against collagenase, which is the cause of collagen absorption in the gingiva and alveolar bone in periodontal disease. Useful for treatment.

Furthermore, since the oral composition according to the present invention contains casein, which is a component of milk protein, it is extremely safe in use regardless of the amount incorporated.

[Test example] Human collagenase inhibitory effect of casein 1, test casein ■αgα carin (Sigma, C-6780) ■β-casein (Sigma, C-6905>■ Casein (Sigma, C-0406) Trypsinized casein was treated with trypsin (Sigma, T)M) e12) at a final concentration of 0.3 mg/ml for 0.5, 10, 30 and 60 min, respectively, at 35°C. (Respectively, the sample name is ni-TO-T5. ni-TIO, ni-
Let T2O and &-T60. ), final concentration 0.3
Tryptic digest of casein with trypsin inactivated with mg/ml soybean trypsin inhibitor.

2. Collagenase The purified collagenase obtained by the method described in Japanese Patent Application No. 1-238941 is used.

3. Measurement of collagenase inhibitory activity The inhibitory activity of test casein against collagenase was measured using test casein measurement buffer (0.2M NaCl, 5mM
Calcium chloride, o, oss amount% Br1j35 and 0
．． 50mM containing 02% sodium azide by volume)
Mix a known amount of collagenase solution with a known amount of collagenase solution and react at 35°C for 10 minutes. t1 (manufactured by Cosmo Bio Inc.) was used as a substrate, and the method of Mizuben et al. (Japanese Jour
nal of Inflation, 4 volumes,
123, 1984) by measuring collagenase activity.

4. Test Results Table 1 shows that among the test caseins, only casein had a dose-dependent collagenase inhibitory activity, and TC
The so value was approximately 30 μg/ml. In contrast, αS- and β-, which are the main components of milk protein,
No inhibitory activity was observed for casein. The inhibitory activity of Ni-casein was inactivated over time by trypsin treatment, indicating that the main activity lies in the Ni-casein protein.

Table - Table [Example-1] Chewing gum casein β -T.

-T5 -TIO -T2O -T2O Final concentration (μg/mff1) 62.5 31.3 15.6 Collagenase inhibition rate (%) 5.0 4.0 82.8 74.3 52.1 20.7 86.4 66.5 48.7 19.3 Chewing gum base of oral composition containing casein as follows: 20.0 powder m
51.9 grapes y7.
10.0 starch syrup
1 casein in 18.0
Pour the whole amount of chewing gum base and the whole amount of starch syrup kept at 0.140°C into a Neegu and knead for 10 minutes, then add 1/3 of the powdered sugar and the whole amount of glucose and mix for 5 minutes.
Next, 1/3 amount of powdered sugar was added and kneaded for 5 minutes.Next, casein was mixed with the remaining 1/3 amount of powdered sugar and then added and kneaded for 5 minutes.[Example 2] Soft Candy - [Example 3] Toothpaste granulated sugar syrup (water 30%) Flavor cutinano pigment - Casein 60.3 56.0 0.3 0.1 0, 1 Preliminary! a.Pour granulated sugar, starch syrup and a small amount of water into a melting pot, bring to a boil to completely melt the granulated sugar,
This mixture was pumped into a vacuum cooker, heated at a vacuum degree of 460 mm Hg and a temperature of 80° C., and then taken out and transferred to a mixing pot.

Next, add casein, fragrance and gardenia pigment, mix thoroughly and spread on a cooling plate.
13 Chikara Raginan 0.9 lauryl g
Sodium acid 1.2 Saccharin
1.0 Butyl paraoxybenzoate
O,OO5 Chlorhexodine digluconate
0.1 fragrance 0.1 part casein 0.05 water
Manufactured according to the residual method. Namely, water, glycerin carrageenan, saccharin, butyl paraoxybenzoate, chlorhexidine digluconate,
After measuring the prescribed amounts of fragrance and casein and mixing them to swell the caking side, add dibasic calcium phosphate sodium lauryl sulfate and mix well.

After defoaming, it is filled into tubes to obtain toothpaste.

[Example 4] A toothpaste was obtained in the same manner as in Example 3, except that the amount of casein added to the toothpaste was 1.0% by weight.

[Example-5] Lozenge Silicic anhydride Magnesium stearate talc Hydroxyprobyl cellulose ni-casein 1.0 0.6 0.3 0°7 0.5 [Example-5] Mouthwash ethanol saccharin sodium fragrance Sucrose fatty acid ester ni-casein 20.0 0, 1 1.0 0.5 0.5 A mouthwash having the above formulation is manufactured according to a conventional method.

Claims (1)

[Claims] (1) An oral composition characterized by containing κ-casein.