JPS6036406B2 - Tooth cleaning composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to tooth cleaning compositions, particularly toothpastes or mouthwashes.

Dextranase is useful as a caries prevention agent because it removes bacteria from the dextran-containing coating on teeth or dental plaque.

However, dextranase has not been available, primarily due to its incompatibility with cellulosic binders or aqueous fluids commonly used in toothpastes.
Dextranase, when combined with cellulosic binders, causes gel-like or cream-like toothpastes to completely lose their hardness and separates the liquid, primarily aqueous, components from the solid composition. This results in cosmetically undesirable products. If the dextranase is combined with an aqueous liquid and with or without a cellulosic binder, the decomposition results in a significant inactivation of the dextranase: surfactants commonly used in tooth cleaning compositions. This decomposition is further strengthened by
Because at least one of these ingredients is present in a typical tooth cleaning composition, typically a cellulosic binder, an aqueous liquid, and a surfactant, the above-mentioned disadvantages prevent tooth cleaning compositions from being used. It was not possible to use dextranase in it.

The object of the present invention is to eliminate these disadvantages and to maintain its hardness even in the presence of a binder and a liquid, primarily an aqueous component, while not losing its activity in the presence of an aqueous liquid alone or a surfactant. It is an object of the present invention to provide a tooth cleaning composition or a mixture which can be used normally in the oral cavity, in particular a toothpaste or a mouthwash. To achieve this purpose, cells.

tooth cleansing agent containing bacterially sourced dextranase in the presence of a base-based binder and optionally a liquid, aqueous component, a binder, or other additives such as abrasives, surfactants, flavoring agents, and fluorinated ingredients. Compositions for use, possibly toothpastes or mouthwashes, are proposed. Surprisingly, tooth cleaning compositions containing dextranase of bacterial origin are selected from the group consisting of chlorides, sulfates, and nitrates of manganese, calcium, and magnesium ion-donating compounds. (hereinafter referred to as component A); and in the case of using bacterially sourced dextranase, 8-indolyl acid, giberelic acid, and/or furfurylaminopurine, etc. (hereinafter referred to as component A). It has been found that the previously known difficulties of separation in the presence of cellulosic binders are eliminated regardless of the presence of a stabilizing activator (referred to as a stabilizing activator).

The presence of a stabilizing active agent also increases the effectiveness of tooth cleaning compositions containing dextranase of bacterial origin, but the use of a stabilizing active agent alone does not reduce the separation. According to a preferred aspect of the invention, 8-indolylacetic acid, giberalic acid and/or furfurylaminopurine may be used as stabilizing active agents for bacterially sourced dextranases, especially in the presence of cellulosic binders. .

The stabilizing active agent, whether the stabilizing active agent is a phytohormone such as 8-indolyl acetic acid or a metal salt as mentioned above, has a range of 0.001 to 0. % by weight may be used. According to the invention, sulfoacetamides, in particular the sodium, potassium or ethanolamine salts of compounds of the general formula R(CH2)2-3NHCOCH2S03, are used as surfactants, where R is the number of carbon atoms. Fatty acid group (fatty acid group)

-), ie R'' contains 11 to 17 carbon atoms.

Preferably, the potassium salt of N-2-ethyllaurate sulfoacetamide is used. This surfactant is 0.0
Preferably, 5% by weight or 5% by weight is used.
．． The dextranase used according to this invention can be produced in various ways.

Dextranase enzymes are commonly used in Penicillium funiculosium.
ium) or from mycogens in a dextran-containing medium or from Leuconostoccum mesenterioides (Fig.
It is obtained in commercial grade from A. rioides).

The latter contains about 95% Q-1,6-glucosidic bonds and about 5% Q-1,3-glucosidic bonds. Dextranase produced from Benicillinium bacteria is particularly 1,6
Hydrolyzes one bond. Dextranase can also be used in a suitable manner, such as in the British Dental Journal J (124
Volume, 196 Gunou April 16th M. 8p, 343-349
2,742,39 minor or by Cuccia et al.
It can also be manufactured according to the method of ``Ofcterjolo Bag'', Vol. 64, p. 513.

According to Bowen, dextranase is ATTCI0
588,903-1600;
rioides) and L. ``Archives of Oral Biology'' outside of Wood, except for propagation with Mesenterioides 25oo.
11, 1066 and below. Additionally, dextranase was added to a flask containing 250ml of growth solution of 0.5% yeast extract and 1% dextran.
enjcillimmfunioulosmm) followed by culturing for 4 days at 30 qo on an incubator.

The culture was then centrifuged for 20 min at 3,000 mC and filter paper (
42) and dialysed against deionized water in a 16-rib "Visking" tube to obtain a
Concentrate to 5,000 ml by dialysis against 5,000 ml of polyethylene glycol. The dextranase produced by this method has a molecular weight of 200,000 and 275.
,000. This may be further purified if desired by fractionation using ammonium sulfate. Bacterial-source dextranases, which are generally produced according to bacterial enzymatic processes, are preferred.

Bacterial source dextranase is Q1,3-dextran or Q1 containing bacterial source dextranase.
, 6-, and Q1,3-, and Q1,4-dextranase by adding a mixture of Bacillus coagulans NR.
It can be obtained from a variant of RL B-3877 (Beckmann Dextranase Catalog No. 680000). Bacterial strains are grown in shaker flasks or acid-locked containers.
5, and can be kept at 40 qo for 1 to 5 days and grown. Sterile growth materials contain carbohydrates such as glucose, sucrose, cellulose or starch and nitrogenous compounds such as ammonium salts, gelatin, casein or protein digests and yeast extracts, corn steeps or stannate salts. The dextran and variants described above together with a mixture of growth stimulants and preservatives, such as the soluble retentate of alcoholic distillation. The enzyme can be concentrated and filtered or subjected to centrifugation to precipitate the cells or intracellular dextranase. Extracellular dextranase can be precipitated using ammonium sulfate, acetone, sodium sulfate or similar salts, and intracellular dextranase is autolyzed and extracted. Following the salt fractionation step, the enzyme can be purified by conventional acid chromatographic methods and can be coagulated or stabilized by the addition of proteins, dextran, salt, etc.; this purification step Usually processed at chilled temperatures. The dextranase content of the tooth cleaning composition of the present invention depends on the dextranase activity measured in Beckman units, which is 1.0% per minute from raw dextran at 3500 and pH 6.0. It corresponds to the amount of enzyme that produces 0 mountain M of reducing sugar.

Bacterial source dextranase with an activity of 90 to 250 units (as determined by Lowry) of 0.004 to 5% by weight can be used.

A dextranase produced by a suitable method and having an activity of 9 protein units of 100 to 150, for example 117, is used in an amount of 0.01 to 0.2% by weight.
The metal ions of manganese(b), calcium and/or magnesium used as stabilizing activators can be obtained from all non-digestive salts,
Water-soluble salts such as sulfates, nitrates, and especially chlorides are preferred.

Stabilizing active agents are typically used for tooth cleaning, unless the tooth cleaning composition is a mouthwash concentrate that has four times the amount of active ingredient due to the intended 3:1 dilution. 0 of the weight of the composition
．． 001 to 0.3%, preferably 0.1 to 0.3
%, most preferably from 0.2% to 0.25%.

After the stabilizing active agent is preferably added to the dextranase, the dextranase is incubated in an incubator for 1 hour at 370 °C before making the final formulation of the tooth cleaning composition.

In this case, the activity of dextranase was determined using the sugar method of Noering and Penfield (“Helvetica simica acta”).
Helv. Chim. Ac. )” Volume 31, p286,
1948). That is, maltose produced by the action of dextranase is quantified photometrically. 0.5%,
Hydrated maltose (C, 2 days, 20,...days 20
) Expresses dextranase activity per milligram.

The tooth cleaning composition of this invention, when it is in the form of a cream or gel toothpaste, contains about 20 suitable ingredients such as an aqueous solution of sorbitol, propylene glycol, and polyethylene glycol 400;
The total water content is 20%, preferably 15%.

The tooth cleaning composition according to the invention, when in the form of a toothpaste or gel, contains dicalcium phosphate as well as resinous abrasive-like condensation products such as melamine and urea with formaldehyde. , dihydrate, dicalcium phosphate (anhydrous), tricalcium phosphate, magnesium carbonate, calcium carbonate, calcium pyrophosphate, calcium sulfate and/or water-impregnable abrasives such as pentonite. Among these, dicalcium phosphate dihydrate, anhydrous dicalcium phosphate and calcium carbonate are preferred.

The amount of abrasive is generally between 20% and 75% of the weight of the toothpaste. The surfactants that are desirable for most tooth cleaning compositions significantly reduce dextranase activity.

However, according to the present invention, a new class of detergents with reduced activity can be used. That is,
A C,2-free, C,8 fatty acid sulfoacetamide in which the N-atom is substituted with a lower alkyl group, having the formula CH3
Particularly preferred is N-2-ethyllaurate potassium sulfoacetamide having (CH2), oNHCOCH2CH2S03K.

It has been found that these special surfactants can coexist with dextranase even in the absence of stabilizing active agents.

Additionally, sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl, and N-palmitoyl sarcosinate may also coexist with dextranase. Other suitable surfactants are nonionic surfactants such as the condensate of sorbitan monostearate and approximately 60 moles of ethylene oxide, and the addition products of ethylene oxide and propylene oxide, and the condensates of propylene glycol. It is a cleaning agent. Binder materials are typically used in amounts up to about 10%, preferably up to about 5%, and most preferably about 0.2-1.5% by weight of the oral composition.

These surfactants are preferably used in an amount of about 0.05 to 5% by weight of the tooth cleaning composition.

The tooth cleaning composition contains silicone, chlorophyll compounds,
No alcohol, menthol, ammonifying substances such as urea or diammonium phosphate, or 0.01, and 5
% by weight, preferably 0.05 to 1.0% by weight of NI-
(4-chlorobenzyl)-W-(2,4-dichlorobenzyl) biguanide; p-chlorophenyl biguanide;
4-chlorobenzhydryl biguanide; 4-chlorobenzhydrylguanylurea; 1,6-di-p-chlorophenylbiguanidohexane; N-3-lauroxypropyl-N5-p-chlorobenzylbiguanide; mono(lauryldimethylammonium) -81 (p-chloro-penzyldimethylammonium) octane dichloride: 5,6
-Jik. Rho2-guanidino-penzimidazole; N
I-p-chlorophenyl-N5-lauryl biguanide;
5-amino-1,3-bis(2-ethylhexyl)-5
-Methylhexahydropyrimidine; 2,2'-dihydroxy-3,5,6,3',5',6'-hexachlorodiphenylmethane;2,2'-dihydroxy-5,5-dicoo diphenylmethane or As well as antimicrobial agents such as their sulfur addition salts, they may contain the usual additives, ie coloring or whitening agents such as titanium dioxide and preservatives such as sodium benzoate. The tooth cleaning composition of the present invention may also contain 0.01 to 5% by weight of flavoring or sweetening agents such as horsetail oil, methyl salicylate, brown sugar, sodium cyclamate or saccharin.

In addition, it contains sodium fluoride, stannous fluoride, potassium fluoride, stannous potassium fluoride (SnF2KF), sodium hexafluorostannate, stannous salt fluoride, sodium fluorozirconate and -fluoride. A fluorine-providing compound such as sodium phosphate is generally used in an amount of 0.0 fluorine.
It may contain 1 to 1%, preferably 0.01%, and a buffer system may optionally be present.

The following experiments demonstrate that mixing Component A increases dextranase activity (Experiment 1) and provides better co-shallowness of bacterial source dextranase and thickening agent on cellulose main structure (Experiment 2). It shows.

Experiment 1 0.067M phosphate buffer containing dextranase (pH 6.0)
．． Dextranase control samples were prepared by mixing 0.5' of phosphate buffer and 2% leuconostoc mecentrioid dextran with 0.4' of phosphate buffer and 2% of leuconostoc mecentrioid dextran.
produced a scream.

This mixture was incubated at 40°C for 45 minutes. The activity of dextranase (Beckman Catalog No. 680,000) was 117 units/female protein. different ingredients A
To prepare a comparable mixture using 0.5 to 0.067M phosphate buffer with dextranase, the dextranase to phosphate buffer ratio was also 5 m/10 m. was added to the phosphate buffer and 2% dextran solution 2.0 skin containing the metal salt to be compared, which was then kept warm in the same way as the control sample,
2.0 of dinitrosalicylic acid, heated to boiling and then cooled in ice, the activity was then determined as a percentage compared to a control sample by the Noering and Bernfield sugar method. 29 as a metal salt solution
．． 4 or 39.6 or 40.6 9/10w [P0
0.02MCaC12-, MnC corresponding to 4-buffer
12-, and 0.025 of the MgC12 solution, and 0.067 in an amount such that the volume of the two solutions is 2.0 solution and the final volume of the sample before incubation is 4.0 secretion each.
Used with M phosphate buffer. At the same time, 0.02
M auxin solution (8-indolyl acetic acid) 0.001
Comparative experiments were conducted using 0.005 and 0.025 secretions, and the results shown in Table 1 were obtained.

・Table 1 Stabilizing active agent in phosphate buffer* Helv. Chim. Acta (volume 31 p286
These values were measured using the method described in
The presence of component A significantly increases dextranase activity.
That is, it clearly shows that the number increases to approximately 5 to 13 tones.

Experiment 2 A cellulose binder and the dextranase obtained by the Bowen method described above [from a non-reactive streptococcal strain or Leuronostoc mesenterioides (Le River on
The viscosity of a composition of carboxymethyl cellulose with dextranase obtained from bacteria was determined to determine its compatibility with ostoc mesen and rioides).

A gel obtained from 100' of glycerin, 39' of carboxymethylcellulose, and 53' of water was used as a control mixture.

Dextranase of bacterial origin (Beckmann dextranase, 117 units of activity/nail 9 protein) was added to the control mixture.
9 out of 10 was added and this gave the results listed in Table D': Table D These values clearly show that the dextranase of bacterial origin does not affect the viscosity.

The invention will be illustrated by the following examples:
Example 1 A toothpaste according to the invention was produced having the following composition: This toothpaste made up to 100% with water had excellent cleaning properties and stability.

For comparison, a storage test was conducted in which the above-mentioned toothpaste paste containing no magnesium chloride and an additional 0.2% by weight of water was used as a control, and this toothpaste was increased to about 50q0 for up to 9 weeks. Ta. The toothpaste of this invention containing 0.2% magnesium chloride was 17 times more stable than the corresponding toothpaste that did not contain this ingredient.

Example 2 A mouthwash having the following composition was manufactured.

This mouthwash concentrate was diluted 3 times with water to obtain an excellent tooth cleaning solution.

Example 3 A mouthwash concentrate was prepared according to the method of Example 2 with the only exception that sodium carboxymethylcellulose was omitted.

Claims (1)

[Scope of Claims] 1. A tooth cleaning composition comprising a cellulosic binder, comprising: bacterial source dextranase; chlorides, sulfates, nitrates and mixtures thereof of ion-providing compounds of manganese (II), calcium, and magnesium; A composition comprising: a component selected from: