WO2006038318A1

WO2006038318A1 - Gingivitis remedial or preventive agent

Info

Publication number: WO2006038318A1
Application number: PCT/JP2005/003868
Authority: WO
Inventors: Yasufumi Itaya
Original assignee: Kobayashi Pharmaceutical Co., Ltd.
Priority date: 2004-09-30
Filing date: 2005-03-07
Publication date: 2006-04-13
Also published as: JP2006096711A

Abstract

[PROBLEMS] To provide an agent capable of easy and effective remedy or prevention of gingivitis, realizing reduced irritation on gingivitis affected parts. [MEANS FOR SOLVING PROBLEMS] Easy and effective remedy or prevention of gingivitis can be attained by the use of an agent comprising a disintegration abrasive and an antibody against whole bacterial cells, or bacterial cell constituents, of Streptococcus mutans. The antibody can be obtained from the foremilk of cow immunized with whole bacterial cells, or bacterial cell constituents, of Streptococcus mutans.

Description

Specification

Gingivitis improving agent or preventive agent

Technical field

[0001] The present invention relates to a gingivitis improving agent or preventive agent. The gingivitis improving agent or preventive agent of the present invention contains an antibody against Streptococcus mutans and a disintegrating abrasive. Background art

[0002] In recent years, the number of patients with gingivitis has increased, and improvement and prevention thereof have been demanded. The major cause of gingivitis is plaque. Plaque adheres directly to the periodontal tissues such as gums and gums, causing inflammation, and also adheres to the tooth surface. The acid produced in the plaque on the tooth surface decalcifies the tooth enamel, causes decoration, and gingivitis is caused by the progress of decoration. In other words, in order to improve and prevent gingivitis, it is necessary to remove not only periodontal tissue but also dental plaque.

[0003] However, when a patient with gingivitis tries to clean the mouth with a conventional dentifrice, the affected area is stimulated and painful, and it is difficult to sufficiently remove plaque. In addition, abrasives contained in dentifrices may damage gums and exacerbate gingivitis. Therefore, it cannot be said that conventional dentifrices have sufficiently improved and prevented gingivitis.

[0004] About 70% of dental plaque is considered to be bacteria, about 20% are polysaccharides formed by bacteria, and about 10% are food residues. Plaque formation is caused by oral bacteria, mainly composed of Streptococcus mutans bacteria, synthesizing polysaccharides from sucrose. On the other hand, it is considered that breast milk obtained by immunizing mice with whole cells of Streptococcus mutans contains antibodies of the bacteria. Thus, a method has been reported in which this breast milk is used to suppress the colonization of Streptococcus mutans bacteria in the oral cavity and prevent decoration (see Patent Document 1). However, this method is effective for improving and preventing gingivitis.

Patent Document 1: Specification of British Patent No. 1505513

Disclosure of the invention

Problems to be solved by the invention [0005] The present invention has been made in view of the circumstances as described above, and is suitable for use by patients with gingivitis and can easily prevent gingivitis in non-patients. I will provide a.

Means for solving the problem

[0006] As a result of diligent studies to solve these problems, the present inventors have found that Streptococcus

'It was found that the improvement or prevention effect of gingivitis can be remarkably enhanced by using an antibody against a whole microbial cell or a bacterial cell component of mutans and a disintegrating abrasive, and the present invention has been completed. That is, the present invention provides the following.

(1) A gingivitis ameliorating agent or preventive agent comprising an antibody against a whole cell or a cell component of Streptococcus mutans and a disintegrating abrasive.

(2) A gingivitis ameliorating agent or preventive agent comprising a colostrum colostrum composition immunized with whole cells or components of Streptococcus mutans and a disintegrating abrasive.

(3) The gingivitis improving or preventing agent according to (2), wherein the content of the colostrum composition is 0.01 to 10% by weight with respect to the total weight of the gingivitis improving or preventing agent.

(4) The cell component is a cell wall fraction, a fibrous structure fraction, a pilus component fraction, a darcosyltransferase fraction, a protein antigen fraction, or a combination thereof of Streptococcus mutans, (2 ) Or (3) gingivitis improving agent or preventive agent.

(5) Streptococcus mutans is a human-type Streptococcus mutans or a mutant thereof, and its serotype is c, d, e, f, or g, (1) one of (4) An agent for improving or preventing gingivitis.

(6) The gingivitis improving agent or preventing agent according to any one of (1) and (5), wherein the disintegrating abrasive comprises disintegrating silica gel.

(7) The gingivitis improving agent or preventing agent according to any one of (1) and (6), wherein the pH of the gingivitis improving agent or preventing agent is in the range of 4-10.

BEST MODE FOR CARRYING OUT THE INVENTION

[0007] The gingivitis improving agent or preventive agent of the present invention comprises an antibody against a whole cell or a cell component of Streptococcus mutans and a disintegrating abrasive. Here, Streptococcus mutans bacteria include mutants. [0008] The antibody against the whole cell or cell component of Streptococcus mutans can be produced by various known production methods, whether it is a polyclonal antibody or a monoclonal antibody. For example, an animal may be immunized with all or a cell component of Streptococcus mutans, and an antibody may be obtained from the secretion or tissue of the animal. A preferred composition containing the antibody includes a composition obtained from breast milk of rush immunized using whole cells or components of Streptococcus mutans as an antigen. Among them, a colostrum composition is preferable.

[0009] As used herein, colostrum refers to milk collected within 24 hours after delivery, and colostrum composition is a composition separated from the colostrum, obtained by processing the colostrum. Composition, and colostrum itself. Immunization of animals such as sushi is carried out using whole cells or components of Streptococcus mutans within one to three months before delivery.

[0010] The colostrum composition may be liquid or solid. Examples of the solid composition include those obtained by converting colostrum into a powder form by freeze drying. Various methods known as formulation methods can be used for the production method of the colostrum composition. The colostrum composition is considered to have an effect of activating the skin in the oral cavity as well as preventing and reducing plaque accumulation.

[0011] Various known bacteria that are not particularly restricted by Streptococcus mutans can be used.

Among them, serotypes preferred by human Streptococcus mutans and mutants thereof are c-types present in the oral cavity of people who prefer c, d, e, f, or g type strains. More preferably, the strain belongs to.

[0012] Streptococcus mutans may be subjected to various known cultures and pretreatments.

. For example, an externally dialyzed solution of BHI medium can be used as the medium, and the grown bacteria can be washed and then treated with formalin.

[0013] Examples of the bacterial cell component include a cell wall fraction, a fibrous structure fraction, a pilus component fraction, a gnolecosyltransferase (GTF) fraction, a protein antigen fraction, and combinations thereof. Each fraction can be obtained by various known methods.

[0014] When a colostrum composition is used, the amount of colostrum composition relative to the total weight of the gingivitis improving agent or preventive agent is 0.01 wt% or more, preferably 1 wt% or more, more preferably 2 wt% or more. In Therefore, it is 30 wt% or less, preferably 20 wt% or less. If it is less than the above range, the effect of colostrum may not be sufficiently obtained, and if it exceeds the above range, it is not economical.

[0015] The gingivitis improving or preventing agent of the present invention contains a disintegrating abrasive. Here, the disintegrating abrasive refers to an abrasive whose average particle diameter decreases when it is subjected to polishing under a load. Disintegrating abrasives not only remove plaque without excessively irritating and abrading the gums and gums, but can also enhance the expression of antibody effects.

[0016] Materials for the disintegrating abrasive include crystalline silica gel, dibasic calcium phosphate dihydrate, dibasic calcium phosphate, anhydrous, monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, insoluble metaphosphate Examples include sodium, aluminosilicate, aluminum oxide, aluminum hydroxide, tribasic magnesium phosphate, magnesium carbonate, magnesium sulfate, titanium oxide, and carbon. These may be used alone or in combination of two or more. These materials are preferably porous.

[0017] The initial average particle size of the disintegrating abrasive is preferably in the range of 9 1 100 / im.

The average particle size after polishing under load is not particularly limited, and is selected according to the use mode of the agent of the present invention. For example, a particle with an average particle size in the range of 0.1-2 μηι after 200 seconds of brushing under a load of 600 g; an initial average particle size of 9 to 100 / im, and brushing under a load of 600 g for 10 seconds Later, particles with an average particle size of 0.5-50 μm can be used.

In this specification, the average particle size and the particle size distribution are expressed as values measured based on laser diffraction and laser scattering methods. “Brushing at a load of 600 g” means that 0.5 g of the agent of the present invention is applied to a toothbrush and brushing is performed with a load of 600 g under the condition of a 300 mm width and 200 strokes per minute. .

[0019] The amount of the disintegrating abrasive with respect to the total weight of the gingivitis improving agent or preventive agent is 5 wt% or more, preferably 10 wt ° / _o , 95 wt% or less, preferably 60 wt% or less.

In the gingivitis improving agent or preventive agent of the present invention, the disintegrating abrasive is considered to bring about an excellent effect by gradually disintegrating in the process of using a load. That is, when a gingivitis improving agent or preventive agent is used as a toothpaste, since it has a relatively large particle size at the start of toothbrushing, large dirt can be efficiently removed. Continue brushing teeth However, when fine particles become dirty, the particles become disintegrated under load and the particle size becomes small, so that the shape becomes effective for removing fine particles. Thus, the change in particle size over time is useful for removing dirt and plaque in the mouth. Furthermore, if the disintegrating abrasive is porous, the particles will disintegrate and the specific surface area will increase if you continue brushing your teeth, so that you can efficiently absorb and remove dirt, plaque, malodorous components, pigments, etc. in the oral cavity. .

[0020] The gingivitis ameliorating agent or preventive agent of the present invention includes other components effective for removing plaque within a range not inhibiting the effects of the present invention; carriers such as gelling agents and solvents; surfactants; It contains various known ingredients such as coloring materials, coloring agents, fragrances, preservatives, and the like.

[0021] Active ingredients other than antibodies and disintegrating abrasives include allantoin, ε-monoaminocaproic acid, tranexamic acid, azulene, vitamins such as vitamin C and sputum, and herbal medicine extracts. Gelling agents include sodium carboxymethylcellulose, methylcellulose, sodium carboxymethylhydroxyethylcellulose, hydroxyethylcellulose, sodium alginate, carrageenan, gum arabic, xanthan gum, tragacanth gum, carragham gum, polyvinyl alcohol, polyacrylic. Examples thereof include sodium acid, carboxybinole polymer, and polybulurpyrrolidone. The content of the gelling agent is usually 0.3-5 wt% with respect to the total weight of the agent of the present invention. Examples of the solvent include water and ethanol. Surfactants include anionic, nonionic, cationic, and zwitterionic surfactants. Examples of the sweetener include sweeteners such as saccharin sodium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perilartine, and p-methoxycinnamic aldehyde. Examples of the fragrances include essential oils such as peppermint and spearmint, 1 menthol, carvone, eugenol, and vanitol.

[0022] The dosage form of the gingivitis improving agent or the preventive agent of the present invention is not particularly limited. The solution may be in the form of a solid preparation such as a cream, paste, tablet, capsule, powder, granule or the like. It may be in the form of a liquid agent such as a suspension or emulsion. Specifically, the gingivitis improving agent or preventive agent according to the present invention includes dentifrice such as toothpaste, powder dentifrice, liquid dentifrice, etc .; mouthwash; intraoral pasta; gingival massage cream; It is provided in various forms such as tablets; lozenges; foods such as chewy / fungam, ice cream and whipped cream. Depending on the purpose of use and mode of use, the amount of colostrum composition and disintegrating abrasive, and Other types and amounts of ingredients are selected.

[0023] The gingivitis improving agent or the preventive agent of the present invention is stored in an appropriate container according to the dosage form and is used. When the gingivitis improving agent or preventive agent of the present invention is a solid agent, for example, when it is in the form of a toothpaste, a toothpaste, a massage cream, etc., the shape of a plastic tube, an aluminum foil laminate tube or the like is variable as a preferable container. Plastic containers; metal containers such as aluminum tubes. When the gingivitis improving agent or preventive agent of the present invention is a liquid agent, for example, in the case of liquid dentifrice or mouthwash, it may be contained in a plastic container such as a PET container. As the container, a light-shielding container is preferable.

[0024] When the gingivitis improving agent or preventive agent of the present invention is a solution or paste, the pH is not necessarily limited, but is typically pH 4 or higher, preferably 5 or higher, more preferably 5. It is 5 or more, 10 or less, preferably 9 or less, more preferably 7.5 or less.

Example

[0025] The present invention will be specifically described below with reference to experimental examples and examples, but the present invention is not limited to these examples.

(Experiment 1)

A paste having the following composition was prepared. The antibody contained in colostrum was used, and disintegrating silica gel was used as a disintegrating abrasive. Colostrum composition was obtained by pulverizing ushi milk collected within 24 hours after delivery by freeze-drying. Usushi was previously immunized with Streptococcus mutans.

[0026] Colostrum composition 10.0% by weight

Disintegrating silica gel (initial average particle size at the time of preparation: 30 μm,

(Brushing under 600g load, average particle size after 200 seconds: 1 μm)

10.0% by weight

Polyoxyethylene polyoxypouylene block copolymer (average molecular weight)

20. 0% by weight

Sodium lauryl sulfate 0.2% by weight

Glycerin 20.0% by weight

Gelatin 0.1% by weight Saccharin sodium 0.5% by weight

Methylparaben 0.3 wt%

Fragrance (Menthol) 1.0% by weight

Ion-exchanged water 37. 9% by weight

Total 10.0% by weight

(Comparative Example 1)

A paste having the following composition was prepared in the same manner as in Example 1 except that the colostrum and adult composition was changed to a component derived from normal ushi milk that was not immunized with Streptococcus mutans. .

[0027] Milk component (Normal ushi milk was pulverized by freeze-drying)

10.0% by weight

(Brushing under 600g load 200 seconds average particle size: 1 μm)

10.0% by weight

Polyoxyethylene polyoxypouylene block copolymer (average molecular weight)

20. 0% by weight

Sodium lauryl sulfate 0.2% by weight

Glycerin 20.0% by weight

Gelatin 0.1% by weight

Sodium saccharin 0.5 weight ^_0/0

Methylparaben 0.3 wt%

Fragrance (salmon menthol)

Ion-exchanged water 37. 9% by weight

Total 10.0% by weight

(Comparative Example 2)

A paste having the following composition was prepared in the same manner as in Comparative Example 1 except that the disintegrating silica gel was changed to a hardly disintegrating silica gel.

Milk component Ordinary ushi milk was pulverized by freeze-drying. ) 10.0% by weight

Hardly disintegrating silica gel (initial average particle size at the time of preparation: 30 / m) 10.0% by weight polyoxyethylene polyoxypropylene block copolymer (average molecular weight)

20. 0% by weight

Sodium lauryl sulfate 0.2% by weight

20. 0% by weight

Gelatin 0.1% by weight

0.5% by weight

Methylparaben 0.3 wt%

Fragrance-menthol)

Ion-exchanged water 37. 9% by weight

Total 10.0% by weight

(Comparative Example 3)

A paste having the following composition was prepared in the same manner as in Example 1 except that the disintegrating silica gel was changed to a hardly disintegrating silica gel.

Colostrum composition 10.0% by weight

Difficult silica gel (Initial preparation)

(Average particle size: 30 μm) 10. 0% by weight

Polyoxyethylene polyoxypouylene block copolymer (average molecular weight)

20. 0% by weight

Sodium lauryl sulfate 0.2

20. 0 weight?

Gelatin 0.1 weight

Saccharin sodium 0.5

Methylparaben 0.3.

Fragrance 0-menthol)

Ion-exchanged water 37.9 straight

Total 10.0% by weight [Evaluation Example 1]

Two patients each with gingivitis were allowed to use the above paste as a dentifrice for 1 week, and a sensory test was conducted. The results are shown in Table 1 below.

[Table 1] Table 1 Improvement effect of gingivitis

◎ Especially excellent

〇 Excellent

厶 Slight effect

X effect not seen

[0031] As can be seen from Table 1, the gingivitis improving or preventing agent of the present invention exhibits excellent performance.

Industrial applicability

[0032] In the present invention, by combining an antibody against a whole cell or a cell component of Streptococcus mutans and a disintegrating abrasive, the effect of improving or preventing gingivitis is improved as compared with the case where each is used alone. Can be improved. Furthermore, the agent for improving or preventing gingivitis of the present invention is suitable for long-time use because there is little irritation to the affected area even when used by gingivitis patients.

Claims

The scope of the claims

[1] A gingivitis ameliorating agent or preventive agent comprising an antibody against a whole cell or a cell component of Streptococcus mutans and a disintegrating abrasive.

[2] A gingivitis ameliorating agent or preventive agent comprising a colostrum composition of urchin immunized with whole cells or components of Streptococcus mutans and a disintegrating abrasive.

[3] The gingivitis improving or preventing agent according to claim 2, wherein the content of the colostrum composition is 0.01 to 10% by weight based on the total weight of the gingivitis improving or preventing agent.

[4] The cell component is a cell wall fraction of Streptococcus mutans, a fibrous structure fraction, a pilus component fraction, a darcosyltransferase fraction, a protein antigen fraction, or a combination thereof. The gingivitis improving agent or preventive agent according to 2 or 3.

[5] The Streptococcus mutans bacterium is a human Streptococcus mutans bacterium or a mutant thereof, and the serotype is c, d, e, f, or g type. The gingivitis improving agent or preventive agent of description.

[6] The gingivitis improving agent or preventive agent according to any one of claims 1 to 5, wherein the disintegrating abrasive contains disintegrating silica gel.

[7] The gingivitis improving or preventing agent according to any one of claims 1 to 6, wherein the gingivitis improving or preventing agent has a pH in the range of 4-10.