JPWO2011092835A1 - Long-lasting bactericidal disinfectant - Google Patents

Abstract

An antibacterial disinfectant for oral cavity comprising a metal ion having an antibacterial action, L-cysteine, L-ascorbic acid, a surfactant other than nonionic, a thickener and an astringent. One or more selected from the group consisting of sorbic acid, sorbate, benzoic acid, benzoate and paraoxybenzoate, sialic acid 5-10 ppm, protein 10-20 ppm and herb extract 100-200 ppm You may further contain 1 type, or 2 or more types chosen from more. The bactericidal antiseptic solution for oral cavity is extremely useful for prevention of oral infections including upper respiratory tract infections and dental fields, for mitigation of inflammation, and for support of treatment, and can be used especially for prevention of influenza and colds.

Description

  The present invention can be used for the prevention of oral infections including upper respiratory tract infections and dental fields, the reduction of inflammation, and as a support for treatment, and is particularly effective for the prevention of influenza and colds. Involved in persistent bactericidal disinfectants.

Microorganisms that were born 300 million years ago and have spread to hundreds of thousands of species since then have had good and bad effects on every aspect of human society and everywhere in nature. One of them is a symbiotic relationship, and ruminant stomach and cellulolytic bacteria, legumes and rhizobia are known as typical examples. Recent examples include Wolbachia as a source of vitamin B group, and the establishment of infection through collaboration between bacteria and influenza virus has also attracted attention as a kind of symbiotic relationship.
This discovery was triggered by a group of dental departments who participated in oral care with the aim of preventing aspiration pneumonia caused by oral disease in elderly care recipients. Of the upper respiratory tract infections (90% cold syndrome), which is the most common disease in daily life, the incidence of influenza is reduced to 1/10 of that in the facility It was drastically reduced. As a result of analysis of the reason, viruses exist due to destruction of protein membranes covering the upper respiratory tract mucosa by resident bacteria (eg, staphylococci) with strong protease (proteolytic enzyme) activity present in the oral cavity and foreign bacteria. The infection mechanism (receptor: sialic acid) is exposed, and a glycoprotein called HA (hemaglythione), which is like a spine on the surface of the virus, is adsorbed, fused, and penetrates into the cell. It was inferred that it was obstructing (Non-Patent Document 1). This new theory of bacteriology is highly theoretically consistent, and in the future, it will be necessary to proceed with extensive clinical trials targeting a wide range of age groups, but “gargle”, which has long been recommended for the prevention of colds, is considered to be toothpaste. Similarly, it is undoubtedly one of the reasonable ways to wash away bacteria and viruses that stick to the mucous membrane of the throat and nutrients in the mouth that is the hotbed of bacterial growth. It goes without saying that gargle is even more desirable if it has a disinfecting effect than just water.
This is because influenza virus genetic mutations are said to be 20 million times faster than humans, regardless of seasonality or new type, and do not deny the effects of vaccines. There are many twists and turns including the prediction of this point, and in that respect, the precautions with the disinfectant can be easily and simply and clearly and effective over a wide range.

However, many experts question the effects of “gargle”. Whatever the reason is gargle
(1) If it is just gargle, it will settle in the oral cavity and throat, and the number of inhabiting bacteria will be slightly reduced, and will be restored soon.
(2) If the virus adsorbs to the throat epithelial cell (mucosa), it will enter the cell in 10 to 15 minutes. In other words, if you don't gargle all the time, you can't prevent infection. This is unrealistic.
(3) Even if gargle is frequently performed, frequent gargles mechanically damage mucosal epithelial cells, which is equivalent to the action of protease.
(4) It also wipes away mucus, the key defense function, to facilitate infection with pathogens.
(5) Conventionally, there is a problem of side effects of gargle for disinfection. For example, a widely used iodine-type gargle is excellent, but mucosal cell damage is recognized, and allergic reactions occur depending on the constitution. It is also contraindicated for people with thyroid disease. There are many people who feel uncomfortable in terms of taste due to the coloring of teeth and clothes. Other commercially available gargles have been pointed out to some extent with side effects.

  By the way, prior to this, the present inventors have developed a universal sterilizing and disinfecting solution having an effective sterilizing and antibacterial action against pathogenic bacteria and viruses (Patent Document 1). "Universal disinfectant" is a basic substance of life, its main ingredient is "amino acids, vitamins, and minerals" as its main component, and it is extremely safe and contains general bacteria, acid-fast bacteria, fungi, spores and It has a wide antibacterial spectrum up to viruses, and it is a disinfectant that is wide and convenient for disinfection, including skin, mucous membranes, wounds, excrement, instruments, equipment, environment, and even plants. Table 1 below outlines the results of the disinfection effect of the universal disinfectant and a known disinfectant.

As for the toxicity of the universal disinfectant, the following results were obtained as a result of tests in the Department of Immunology, Kinki University School of Medicine.
(1) LD50 in mice is orally administered (po) 1mL Estimated 10mL ... 18L converted to human
(2) Intraperitoneal administration (ip): 4 mL ... 7.2 L in terms of human
(3) Animal cells (monkey kidney CV-1 and human lymphocytes) are diluted 10 times and about half of the cells grow without any damage (4) No abnormalities are observed even when applied to the skin for a long time From the above test results, it is no exaggeration to say that the safety of “universal sterilizing liquid” is equivalent to that of ordinary drinking water and mineral water.

  In Example 4 of Patent Document 1, when a universal sterilizing solution is used as gargle water, it has an equivalent disinfecting effect as compared to the conventional poppyyon iodine, and the gargle effect lasts for 60 minutes. It has been confirmed that it is superior in terms of safety and safety.

International Publication No. 2009/133616 Pamphlet

Mieko Adachi et al., Geriatric Dental Medicine Vol. 22, No. 2, pp. 83-88, 2007

  Therefore, when the gargle effect using the all-purpose sterilizing disinfectant solution of Patent Document 1 was further tested over time, when the number of bacteria before gargle was 100%, it was about 30% in about 3 hours after gargle. Obtaining the knowledge that the number of bacteria has recovered, it was found that there is room for further study on the sustainability of the disinfection effect in order to use the universal disinfectant disinfectant solution as gargle water.

  Therefore, the present invention eliminates the drawbacks of the conventional gargles described above and further reaches the upper respiratory tract infections, oral infections and dental infections including the block of influenza infection system based on the new theory. Effective for the prevention and treatment of inflammation, relief of inflammation and removal of bad breath, and can be used safely for multiple purposes. It has excellent disinfection effect and has excellent disinfection effect. The object is to provide a liquid.

  As a result of intensive studies, the present inventors have improved the disinfection effect against viruses and bacteria than the universal disinfection solution by mixing a thickener and an astringent with the universal disinfection solution described in Patent Document 1. In addition, the present invention has been completed by successfully increasing the sustainability of the disinfection effect.

That is, the present invention
[1] An antibacterial disinfectant for oral cavity, comprising a metal ion having antibacterial action, L-cysteine, L-ascorbic acid, a non-ionic surfactant, a thickener and an astringent,
[2] Antibacterial metal ions are trivalent iron ions (Fe ³⁺ ), divalent iron ions (Fe ²⁺ ), zinc ions (Zn ²⁺ ), copper ions (Cu ²⁺ ), cobalt ions (1), or two or more selected from the group consisting of (Co ²⁺ ), nickel ions (Ni ²⁺ ) and silver ions (Ag ⁺ );
[3] The concentration of metal ions having antibacterial action is 50 to 200 ppm for III-valent iron ions, 110 to 400 ppm for II-valent iron ions, 7.5 to 125 ppm for zinc ions, 15 to 60 ppm for copper ions, cobalt The bactericidal disinfectant for oral cavity according to the above [2], which is 180 to 300 ppm for ions, 85 to 175 ppm for nickel ions, and 1 to 3 ppm for silver ions,
[4] The bactericidal antiseptic solution for oral cavity according to any one of [1] to [3], wherein the concentration of L-cysteine is 100 to 1000 ppm and the concentration of L-ascorbic acid is 100 to 500 ppm,
[5] Surfactants other than nonionic are alkylbenzene sulfonate, linear alkylbenzene sulfonate, polyoxyethylene alkyl ether sulfate, higher alcohol sulfate, sodium lauryl sulfate, lauroyl sarcosine sodium, stearyl dimethyl chloride Any one of [1] to [4] selected from the group consisting of benzeneammonium chloride, benzalkonium chloride, benzenetonium chloride, alkyldiaminoethylglycine chloride and alkylpolyaminoethylglycine hydrochloride. Bactericidal disinfectant for oral cavity,
[6] The bactericidal antiseptic solution for oral cavity according to any one of the above [1] to [5], wherein the concentration of the surfactant excluding nonionic is 20 to 100 ppm,
[7] The oral cavity according to any one of [1] to [6], wherein the thickener is one or more selected from the group consisting of corn starch, agar, sodium alginate, chondroitin sulfate and hyaluronic acid. Disinfectant,
[8] When the concentration of the thickener is singly added, it is 20000 to 35000 ppm for corn starch, 1000 to 1500 ppm for agar, 5000 to 8000 ppm for sodium alginate, 8000 to 15000 ppm for chondroitin sulfate, and 3000 to 5000 ppm for hyaluronic acid. The bactericidal disinfectant for oral cavity according to the above [7],
[9] The bactericidal antiseptic solution for oral cavity according to any one of the above [1] to [8], wherein the astringent is alum, catechin, bittern or hop extract,
[10] The bactericidal antiseptic solution for oral cavity according to [9], wherein the concentration of the astringent is 8000 to 12000 ppm for alums, 5000 to 10000 ppm for catechins, 8000 to 20000 ppm for bitterns, 10000 to 15000 ppm for hop extract,
[11] The method according to any one of [1] to [10], further including one or more selected from the group consisting of sorbic acid, sorbate, benzoic acid, benzoate, and paraoxybenzoate. Bactericidal disinfectant for oral cavity,
[12] The bactericidal antiseptic solution for oral cavity according to the above [11], wherein the concentration of sorbic acid, sorbate, benzoic acid, benzoate and paraoxin benzoate is 50 to 100 ppm,
[13] Any one of [1] to [12], further including one or more selected from the group consisting of 5 to 10 ppm of sialic acid, 10 to 20 ppm of protein, and 100 to 200 ppm of herbal extract or essential oil. Bactericidal disinfectant for oral cavity,
[14] One or more herbal extracts or essential oils selected from the group consisting of eucalyptus, mint, chamomile, lavender, oregano, glove, rosemary, thyme, neroli, pine, bergamot, cedarwood, hinokitiol, and tea tree oil The bactericidal disinfectant for oral cavity according to the above [13],
[15] The bactericidal antiseptic solution for oral cavity according to any one of the above [1] to [14], wherein the pH is adjusted within a range of 2.5 to 4.0,
[16] Sterilization for oral cavity according to any one of [1] to [15], wherein the relative viscosity is 1.5 to 2.2 when the viscosity of tap water is 1 as measured by an Ostwald relative viscometer. Regarding disinfectant.

The bactericidal disinfectant for oral cavity of the present invention is excellent in safety, excellent in bactericidal disinfection against viruses and bacteria, and excellent in sustainability of the effect. It is possible to prevent various diseases that develop due to oral or upper respiratory tract infection for a long time. Therefore, the infection of the disease can be efficiently prevented by regularly gargle and rinse the mouth about 3 to 4 times a day.
In addition, by enabling sterilization of causative bacteria of caries existing in the oral cavity, oral care such as prevention of dental caries and bad breath can be achieved.

  As described above, the present invention was developed based on Patent Document 1, and the following components described in Patent Document 1 can be incorporated into the present invention.

(1) Metal ion having antibacterial action The metal ion having antibacterial action may be any metal ion used in Patent Document 1, for example, III-valent iron ion (Fe ³⁺ ), II-valent iron. ^Examples include ions (Fe ²⁺ ), zinc ions (Zn ²⁺ ), copper ions (Cu ²⁺ ), cobalt ions (Co ²⁺ ), nickel ions (Ni ²⁺ ), and silver ions (Ag ⁺ ). These metal ions may be used alone or in combination.
The amount of the metal ions in the bactericidal antiseptic solution for oral cavity of the present invention may be appropriately adjusted so as to obtain a desired bactericidal power. For example, iron ions are 50 to 200 ppm, and II-valent iron ions are 110. It is preferable to be -400 ppm, 7.5-125 ppm for zinc ions, 15-60 ppm for copper ions, 180-300 ppm for cobalt ions, 85-175 ppm for nickel ions, and 1-3 ppm for silver ions.

Moreover, as said metal ion, what is necessary is just to use the said various compounds which are soluble in water and become ion, for example. For example, for Fe ³⁺ ions, ferric chloride, ferric nitrate hexahydrate, ferric nitrate nonahydrate, ferric nitrate n hydrate, ferric phosphate n water Japanese, ferric citrate, n-hydrate, etc., Fe ²⁺ ions, iron chloride, tetrahydrate, gluconate, iron citrate, iron oxalate, etc., Zn ²⁺ , zinc citrate Dihydrate, zinc gluconate, etc., Cu ²⁺ for copper chloride, dihydrate, diammonium copper chloride, dihydrate, copper nitrate, trihydrate, etc., Co ²⁺ , cobalt gluconate Trihydrate, cobalt hydroxide, cobalt citrate, etc., Ni ²⁺ includes nickel nitrate and the like, and Ag ⁺ includes silver sulfate, silver phosphate and the like.

(2) L-Cysteine L-cysteine is a kind of sulfur-containing amino acid and is an essential component for skin metabolism, assists the production of collagen and cooperates with L-ascorbic acid to suppress the generation of melanin. It is a major component of skin, nails and hair and is widely distributed throughout the body. Surprisingly, L-cysteine itself not only exhibits an antibacterial action depending on how it is used, but also has an SH group (a thiol group in which sulfur and hydrogen are bonded) and an antibacterial metal ion in the molecular structure. Amplifies strong bactericidal properties, promotes the destruction of cells by inhibiting DNA, inactivating enzymes, inhibiting metabolic functions, denaturing proteins or generating free radicals. It contributes to the stability of the component by strong antioxidant action and reducing action, has high biocompatibility, strongly adheres to pathogens, and thus plays a role of promoting permeability. The optimum concentration differs slightly depending on the type and concentration of metal ions contained, but is preferably several times the ion concentration. For example, the content of L-cysteine in the sterilizing solution of the present invention is preferably 100 to 1000 ppm.

(3) L-ascorbic acid The action of L-ascorbic acid is as described above. The content of L-ascorbic acid in the bactericidal antiseptic solution for oral cavity of the present invention is preferably 100 to 500 ppm.

(4) Surfactant Excluding Nonionic System As the surfactant excluding the nonionic system, the surfactant used in Patent Document 1 may be used. Examples include ionic surfactants and amphoteric surfactants.
(Anionic surfactant)
Alkylbenzene sulfonate (ABS), linear alkyl benzene sulfonate (LAS), polyoxyethylene alkyl ether sulfate (AES), sodium lauryl sulfate, sodium lauroyl sarcosine, higher alcohol sulfate (AS)
(Cationic surfactant)
Stearyldimethylbenzylammonium chloride, benzalkonium chloride, benzethonium chloride (amphoteric surfactant)
Alkyldiaminoethylglycine hydrochloride, alkylpolyaminoethylglycine hydrochloride The surfactants other than the nonionic system may be used alone or in combination of two or more.

  In the bactericidal antiseptic solution for oral cavity of the present invention, the bactericidal action is amplified and the bactericidal time is remarkably shortened by containing 20 to 100 ppm of the surfactant excluding the nonionic system.

(5) Others The bactericidal disinfectant for oral cavity of the present invention contains at least one selected from the group consisting of sorbic acid, sorbate, benzoic acid, benzoate, and paraoxybenzoate esters, so that it can be sterilized. It becomes possible to improve power.
Examples of the sorbate include potassium sorbate and sodium sorbate.
Examples of the benzoate include potassium benzoate, sodium benzoate, calcium benzoate, ammonium benzoate, and zinc benzoate.
Examples of the paraoxybenzoates include isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate, and propyl paraoxybenzoate.
The concentration of the sorbic acid, potassium sorbate, benzoic acid, benzoate, and paraoxybenzoic acid esters in the bactericidal antiseptic solution for oral cavity is preferably 50 to 100 ppm.

  Next, in developing the bactericidal disinfectant for oral cavity of the present invention, the components added to the universal bactericidal disinfectant described in Patent Document 1 were examined.

<Manufacture of universal sterilization solution>
Production example A
Solution I: 0.96 g of ferric chloride hexahydrate (FeCl ₃ .6H ₂ O) is dissolved in 200 ml of purified water.
Solution II: 1 g of L-cysteine, 0.1 g of L-ascorbic acid, 0.05 g of potassium sorbate, and 0.1 g of sodium lauryl sulfate are dissolved in 800 ml of purified water.
Next, Solution I and Solution II were mixed and 0.6 ml of 1N hydrochloric acid was added to adjust to pH 3.0 to produce a universal sterilizing solution.

  Hereinafter, various universal sterilization disinfectants were produced by the same production method, and designated as Production Examples B, C, D, and E.

  As is apparent from the above composition, the “universal sterilizing solution” is composed of safe components and has a broad antibacterial spectrum. Therefore, the following examination was carried out for the purpose of maintaining the antiseptic effect while maintaining this antibacterial spectrum.

(1) Viscosity In conventional gargles, not only bacteria, viruses and dust, but also mucus adhering to the mucous membrane, which is the key to the defense function from external enemies, is washed away, and the mucous membrane becomes apparent. It was pointed out that it was giving the chance of infection. For example, it is known that if the mucus on the frog's body surface is removed with a detergent, it will soon infect the mildew and will eventually die. However, there is a suspicion that a similar phenomenon occurs in conventional gargles.

  Therefore, the present inventors have speculated that the outflow of this mucus may be partially solved by giving viscosity to the gargle without replacing the mucus. This is because it is assumed that by replacing mucus, which is originally present, by covering the mucous membrane with the mucous membrane, it is possible to capture viruses and bacteria, which are external enemies, with mucus while maintaining the effect of conventional gargle. .

(Bactericidal artificial mucus)
Prior to the experiment, we asked 20 men and women of all ages to monitor how viscous they could be without unease and resistance.

  An Ostwald relative viscometer was used for measuring the viscosity. The principle is to measure the relative viscosity by measuring the time during which the liquid surface that sucks up the sample liquid under a constant temperature passes through the score lines L1 to L2 by its own weight. By the way, the viscosity of the “universal sterilization liquid” was 1 as equal to tap water. As a result, it was concluded that gargle can be performed without any discomfort if the relative viscosity is 2.2 or less, although there are individual differences. The viscosity was adjusted by adding a food thickener (starch, dietary fiber, etc.) to the universal sterilizing solution.

  Next, relative viscosity with a thickener (starch, dietary fiber, etc.) added to various foods in place of the purified water used in producing the representative examples A, B, and C of the universal sterilizing solution. It was decided to verify the sterilizing effect of the test disinfecting liquids a1, b1, and c1 prepared using the liquid adjusted to 2.

As representative test bacteria, S. aureus 209P as a representative of Gram-negative (-) bacteria. E. coli O-157 was adopted. Each bacterial suspension (1 × 10 ⁹ cells / saline water) was dropped into the viscous test disinfectants a1, b1, and c1 so as to be 1% by weight, and one platinum ear-fishing fungus over time. Then, it was inoculated into ordinary broth and agitated and cultured at 37 ° C. under aerobic condition. And the grade of the bactericidal disinfection effect was determined by the presence or absence of the proliferation of bacteria. The results are shown in Table 4 below.

The sterilizing power of universal sterilizing liquids A, B, and C prepared with purified water is expressed as “++” for convenience.
++: There is no significant difference between the sterilizing power of the universal sterilizing solution and the test sterilizing solution. ++: The sterilizing power of the test disinfecting solution decreases and sterilization takes time. ++: The sterilizing power of the test disinfecting solution. Fell considerably. Cannot be used-: The sterilizing power of the test disinfectant is inactivated.

  As is clear from the results shown in Table 4, the sterilizing power was reduced depending on the type of thickener added. This decrease was confirmed to be deeply involved in the weakening of spores and viruses.

  A wide variety of thickeners other than those listed above were tested, and corn starch, agar, sodium alginate, chondroitin sulfate, hyaluronic acid are suitable as thickeners for all-purpose disinfectants and used in combination. It proved that there was no problem.

Next, the degree of adhesion of the disinfectant solution to the mucous membrane was observed.
15 minutes from the upper gingival area where scouring is carried out 15 times 3 times once with a test disinfecting solution containing 0.15% agar in the all-purpose disinfecting disinfecting solution A and having a relative viscosity of 2.2, and once for 15 seconds 3 times. When a simple bacterial test was performed in which the bacteria were caught with a platinum loop every time, it was observed that the bacteria were almost aseptic for about 30 minutes and then gradually increased. That is, although this viscous liquid is gradually released from the mucous membrane, it is said that it adheres to the gingiva in a state where the sterilizing ability is sufficiently maintained for about 1 hour.

In addition, as a result of searching for a simpler inspection method, 0.05% of food additive Dye Blue No. 2 was added to the test disinfectant and gargled, and the blue color attached to the gums and oral mucosa By visually observing the process of fading, it was found that there was an approximate parallel relationship with the actual bacterial test. In the following tests, the addition of Blue No. 2 was added. Adopted. Bacteriological tests were also conducted at key test points. In addition, when the lower limit of relative viscosity was calculated | required by the said test method, the conclusion that 1.5 was required was obtained. Therefore, the relative viscosity is preferably 1.5 to 2.2.
As a result of the experiment, the ranges of the concentrations of various thickeners exhibiting the above viscosity are as shown in Table 5 below.

  However, it was difficult to say that the persistence of the sterilizing and sterilizing effect by gargle was improved by one step or two steps only by applying viscosity as described later.

(2) Application of astringent action Astringent action means that a protein in the vicinity of the surface of the mucous membrane or skin is temporarily or continuously reversibly coagulated and denatured to produce a water-insoluble substance. In this way, by applying a dense barrier on the surface of the mucous membrane or skin, the effect of alleviating external irritation and improving antiseptic, analgesic, texture, etc. is shown. In particular, the throat is covered with a pleated mucous membrane and is strongly converging.

  Examples of foods and food additives having an astringent action include alum, catechin (tannin), bittern, hop extract and the like.

  Test disinfectants a2, b2, and c2 obtained by adding various concentrations of astringents to the all-purpose disinfectant disinfectants A, B, and C have a concentration that does not cause discomfort or discomfort in the oral cavity or throat by 20 people. It was monitored and the bactericidal power when the upper limit concentration was added was verified in the same manner as in Table 4.

As is apparent from the results in Table 6, the astringent had little effect on the bactericidal activity regardless of the type.
Next, when gargle was performed with the test disinfectant a2, the sterilization duration on the mucous membrane was measured. When 0.05% amount of Blue No. 2 was added and observed in the upper gingival part, it varied slightly depending on the type of astringent, but about 1.5 hours for alum, 2 hours for catechin, 1 hour for bittern and hop extract Strongly effective. The results are shown in Table 7.

  Table 7 shows the results of the test disinfectant a2, but the test disinfectants b2 and c2 showed similar results.

  In addition to the determination with the pigment, the change of the bacteria was measured according to a conventional method by wiping with a sterile gauze while changing the location of the upper gingival part with the passage of time, but the results were similar to the above table. For example, catechins were almost aseptic until about 90 minutes, and the appearance of bacteria was gradually observed thereafter, but after 180 minutes, the number of bacteria was 10-15% before gargle. The mechanism by which the sterilization effect by gargle continues is that the mucous membrane shrinks due to the astringent action, and the antiseptic solution is embraced and covered with an insoluble thin film, resulting in a double strong barrier on the mucosa, such as viruses and bacteria It is inferred that pathogens block the adhesion to mucous membranes and skin surfaces.

  In addition, as an astringent, it is excellent in bactericidal power and its sustainability when used alone rather than adding different kinds of astringents, and the optimum concentration is 8000 to 12000 ppm for alums, and 5000 to catechins. It was confirmed that it was 10,000 ppm, bitterns 8000-20000 ppm, and hop extract 10000-15000 ppm.

  In addition, several types of compounds exist as alums and catechins. In addition, bitterns are bitter liquids remaining after the salt extracted by boiling seawater, and the main components thereof include magnesium sulfate, and magnesium chloride, sodium chloride, potassium chloride and the like. Although it is generally used for coagulation of tofu, it has been elucidated that it has a fat absorption inhibitory action and a blood sugar inhibitory action, and is now applied to various foods and cosmetics. Meanwhile, catechins have been confirmed to have various pharmacological effects such as antibacterial activity, antiviral activity, antioxidant activity, anticancer activity, and detoxification activity.

(3) Combination of Viscosity and Convergence Based on the above test results, it was decided to verify the effect when viscosity and astringency were imparted.

  Table 8 shows a part of the results of the bactericidal disinfectant E for oral cavity obtained by adding various effective thickeners and astringents to the universal disinfectant disinfectant E.

As a result of the above combination test, the duration of sterilizing power by gargle with the addition of the thickener alone was about 1 hour, and the duration of the astringent alone was about 2 hours. The synergistic effect of extending was expressed. Although not all bacteria in the mouth were killed, the bactericidal effect lasted for 5 to 7 hours on the mucous membrane. Moreover, it took 6 hours for the number of bacteria in saliva to be 10-15% before gargle.
The results in Table 8 are the results when the universal sterilizing liquid E is used as a base, but similar good results are obtained when the universal sterilizing liquids A to D are used as a base.

  From the above, the thickener used in the bactericidal antiseptic solution for oral cavity of the present invention is one or more selected from the group consisting of corn starch, agar, sodium alginate, chondroitin sulfate and hyaluronic acid. It is preferable. In addition, when added alone as a thickener concentration, it should be 20000-35000 ppm for corn starch, 1000-1500 ppm for agar, 5000-8000 ppm for sodium alginate, 8000-15000 ppm for chondroitin sulfate, 3000-5000 ppm for hyaluronic acid. Is preferred.

  Moreover, as an astringent used for the bactericidal disinfectant for oral cavity of this invention, it is preferable that it is 1 type chosen from the group which consists of alums, catechins, bitterns, and a hop extract. The concentration of the astringent is preferably 8000 to 12000 ppm for alums, 5000 to 10000 ppm for catechins, 8000 to 20000 ppm for bitterns, and 10,000 to 15000 ppm for hop extract.

(4) Further improvement of potency of bactericidal antiseptic solution for oral cavity (I) Improvement of affinity for mucous membrane The main components of bactericidal disinfecting solution for oral cavity are amino acids, vitamins and minerals that are basic components of living body. As a result of earnestly pursuing to give higher affinity to mucous membranes, it was found that certain herbal extracts and essential oils are effective.
The herb extract or essential oil includes one or more selected from the group consisting of eucalyptus, mint, chamomile, lavender, oregano, glove, rosemary, thyme, neroli, pine, bergamot, cedarwood, hinokitiol and tea tree oil. Can be mentioned.

  By including the herb extract or essential oil in the bactericidal antiseptic solution for oral cavity, there is an advantage that not only the affinity to the mucous membrane is improved but also antibacterial activity is exhibited and excellent anti-inflammatory properties are exhibited. Furthermore, the fragrance of herbal extracts and essential oils reaches the limbic system directly through the mucous membranes, which is transmitted to the hypothalamus to stimulate the autonomic nervous system and hormone system, and the neurochemical substances involved in each are secreted. It is also expected to stimulate the immune system by adjusting the balance between the mind and body. Also, it has been scientifically confirmed that inhaled lungs are diffused and sent to capillaries throughout the body to produce a unique medicinal effect.

By adding appropriate amounts (100-200 ppm) of these herbal extracts and essential oils, it is linked to a number of physiological functions including anti-inflammatory action accompanying taste and smell and contributes to further enhancement of added value. Yeah. Furthermore, the persistence of the bactericidal effect was increased by an average of 1 to 1 and a half hours due to the improvement of the affinity for mucous membranes, and among them, the addition of eucalyptus and mint exceeded 8 hours.
The herbal scent itself disappears naturally from the mouth about 30 minutes after gargle.

(II) Addition of influenza virus infection-preventing substances (a) Influenza is infected because hemagglutinin (HA), which is like a number of spines on the surface of the virus, adsorbs to sialic acid present in epithelial cells of the mucosa. Begins. Therefore, by containing a small amount of sialic acid (5 to 10 ppm) in the bactericidal antiseptic solution for oral cavity, even if a large amount of virus enters the respiratory tract, it is first adsorbed on this sialic acid, and the viscous oral bactericidal disinfection There is an advantage that the virus is entangled in the liquid and deactivated in a few minutes. Even if time elapses after gargle and the efficacy of gargle water drops, it is not easy to reach mucosal cells if the virus adsorbs to the sialic acid contained.

(B) Addition of protein (Protein) Viral infection is facilitated by a highly active protease produced by certain bacteria in the oral cavity that damages epithelial cells in the throat. By including protein in the bactericidal antiseptic solution for oral use to prevent this action, the existing protease has the advantage that the contained protein is first degraded, inactivated and disappeared, making virus infection difficult. The type of protein is not particularly selected and a minute amount of 10 to 20 ppm is sufficient, and this concentration does not affect the bactericidal effect of the bactericidal disinfectant for oral cavity.

  In addition, the bactericidal disinfectant for oral cavity of this invention can be prepared by adding and mixing the said various components to water or heated water. The order of addition is not particularly limited. Moreover, water used as a medium also includes tap water, ion exchange water, pure water, purified water, etc., and may be appropriately selected according to the purpose of use.

  Moreover, in the bactericidal antiseptic solution for oral cavity of this invention, by adjusting to acidity, it contributes to the maintenance and stability of the titer of the component of a bactericidal disinfecting solution, and supports the penetration | invasion inside a pathogen. The pH of the sterilizing / disinfecting solution of the present invention is preferably 2.5 to 4.0. A known pH adjuster can be used for adjusting the pH.

  Note that sterilization as used in the present invention refers to killing bacteria present in the oral cavity. Moreover, it can be said that the disinfection and sterilization in the present invention have a remarkable effect that is different from conventional products in that the effect is sustained. Here, when gargle is performed using a conventional gargle, the number of bacteria in the oral cavity is recovered over time even if it is once reduced. On the other hand, in the present invention, recovery of the number of bacteria in the oral cavity after gargle can be significantly delayed.

In addition, the pathogen referred to in the present invention refers to viruses and bacteria that can cause disease by infection from the oral or upper respiratory tract, and is a causative agent of various infectious diseases such as intestinal infections and respiratory infections, Salmonella ( Salmonella spp.), Shigella spp., Vibrio parahaemolyticus, Vibrio choreae, Escherichia coli O-157, Campylobacter jejuni, pseudomembranous colitis (Clostridium difficile), Clostridium perfringens, Yersinia enterocolitica, Helicobacter pylori, Ameba Shigella (Entemoeba histolytica), Bacillusu cereus, Staphylococcus scus Clostridium botulinum, Haemophilus influenzae, Streptococcus pneumoniae, Chlamiadia pneumoniae, Legionella lung Bacteria (Legionella pneumoniae), Branhamella catarrhalis, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Type A streptococci (Storeptcoccus pyogenes), Corynebacterium diphtheellae pertussis, pertussis B, pertussis B (Chramidia psittaci), methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Proteus spp. Acinetobacter spp.), Enterococcus faecalis, Staphylococcus saprophyticus, type B streptococci (Storeptcoccus agalactiae), and the like.
Examples of the virus in the present invention include influenza virus, rhinovirus, coronavirus, adenovirus, RS virus, avian influenza virus, norovirus, hepatitis virus, AIDS virus, rotavirus and the like.

In the present invention, it is possible to prevent infection of the pathogen from the oral or respiratory tract by sterilizing the mucous membrane such as the oral cavity and throat with the bactericidal disinfectant for oral cavity of the present invention by gargle, rinsing, etc. become. In addition, the bactericidal disinfectant for oral cavity of the present invention is composed of components with little irritation, and can be used for disinfection in the nasal cavity, which is another infection route.
In addition, even in non-human animals, it is possible to prevent infection of the pathogen by including the oral sterilization liquid of the present invention in the oral cavity or by sterilizing the nasal cavity.
As a method for disinfecting the oral cavity and nasal cavity, conventional methods may be used.For example, in addition to gargle and rinsing, the oral cavity is sprayed with an oral bactericidal disinfectant or a swab containing an oral bactericidal disinfectant. Or what is necessary is just to contact the surface of a nasal cavity.
Examples of non-human animals include domestic animals such as cats, dogs, rabbits, chickens, sheep, goats, pigs, cows and horses.

  It should be noted that the dose of oral bactericidal disinfectant appropriate to ensure the preventive pharmaceutical benefit is selected according to parameters known to those skilled in the art, such as the age, sex, and weight of a human or non-human animal.

  As described above, the bactericidal antiseptic solution for oral cavity of the present invention is composed of components having excellent safety, and in addition to excellent bactericidal disinfection, viscosity and astringency are combined to prevent infection. It is presumed that an insoluble barrier is placed on the target mucosa or skin surface and a viscous bactericidal antiseptic solution is contained on the mucosa or skin surface to prevent infection by pathogens such as viruses and bacteria.

  In addition to this, there is a strong double barrier, and by including sialic acid and / or protein in the bactericidal antiseptic solution for oral cavity, infection prevention can be further strengthened. Furthermore, by including herbal extract or essential oil in the bactericidal disinfectant for oral cavity, the mucosal hydrophilicity and physiological action of herbal extract or essential oil are synergistic, and a convenient five-fold defense system is constructed, and the pathogen remains alive. By demonstrating a defense function that is not brought close to or close to cells, it is possible to significantly extend the sterilization effect of gargle compared to conventional gargle water.

  Hereinafter, specific production examples and examples will be described, but the gist of the present invention is not limited thereto. The gargle water of the present invention can be produced in various ways by combining the constituents of the present invention and the concentration thereof, but here, it is limited to a representative example and adopted in the examples described later.

  The basic production method is preferably a method in which a solution [α] containing metal ions and [β] containing components other than metal ions are separately produced and mixed together (solution [α] + It is preferable that the thickener contained in the solution [β] is dissolved in advance by heating alone and the other components are added and dissolved in the solution.

  The respective volumes of the solution [α] and the solution [β] may be equal to each other, but preferably about 1: 9 or 2: 8 can prevent troubles of precipitation of components. Dilute hydrochloric acid is preferable for adjusting the pH (2.5 to 4.0).

[Production Example 1]
<Solution α>: 0.96 g of ferric chloride hexahydrate is dissolved in 200 ml of water.
<Solution β>: 8 g of sodium alginate is added to 800 ml of water and dissolved by humidification.
L-cysteine 1 g, L-ascorbic acid 0.1 g, potassium sorbate 0.05 g, sodium lauryl sulfate 0.1 g, alum (potassium aluminum sulfate) 8 g, L-menthol 0.2 g, sialic acid 5 mg, protein Add 10 mg of powder (from soybean) and dissolve.

Next, <Solution α> and <Solution β> were mixed and prepared by adding 0.6 ml of 1N hydrochloric acid.
Thereafter, the bactericidal antiseptic solution for oral cavity (abbreviated as “gargle water”) of the present invention was produced in the same manner, and the production examples were summarized as Tables 9-1 and 9-2 as 2 to 8.

<Test Example 1>
When gargling, I decided to look at the outline of the effect by the number of viable bacteria present in the saliva. Production Examples 1 and 2, as a comparison, gargle with only water, a widely used iodine-based gargle, and universal disinfectant A were also tested. 3 people in each test area, gargle 3 times for 20 seconds each time, immediately after that, 30 minutes later, 1 hour later, 0.5 ml of saliva collected every hour thereafter, and the number of viable bacteria present in 1 ml of saliva Measurement was performed according to a conventional method. The results are shown in Table 10. The numbers in the table are approximate values for the average of three people. The number in the parenthesis indicates the ratio of the number of bacteria when the number of bacteria before gargling is 100. During the measurement time, it was forbidden to eat or drink anything for the sake of accuracy.

As is clear from the results shown in Table 10, the number of bacteria just after gargle with tap water is only 5%. However, it was found that the number of bacteria returned to its original value as time passed.
On the other hand, in the case of popidone iodine recommended as a mouthwash, it decreased to 2% immediately afterwards, but then gradually increased to a level of 30% after 1 hour, and returned to 5% after 5 hours. When the universal disinfectant was used, it was maintained at 2% immediately and 15% after 1 hour, but after 8 hours, it returned to the original number of bacteria.
On the other hand, when this gargle water is used, the bacteria are not detected until 15 minutes later, appear for the first time after 30 minutes, 3-5% even after 1 o'clock, and maintain the same level for a while after that, gradually from 6 hours later It started to increase, and after 8 hours, about 20% (same level as 1 to 1.5 hours of universal disinfectant), it took 12 hours or more to recover to the original number of bacteria.
Although the number of bacteria in saliva is different from the number of bacteria on the mucous membrane, it can be said that the effect of the present gargle can be maintained for at least 8 hours. Therefore, using this gargle water, for example, gargle three times a day in the morning, noon, and evening, it is extremely effective in preventing infection against pathogens that cause infection from the oral and upper respiratory tract. Is estimated to be obtained.

<Test Example 2>
Next, the change in the number of viable bacteria present on the mucous membranes of three subjects was examined when gargled with gargle water prepared in Production Example 3. Saliva also adheres to the mucous membranes. Based on the assumption that the result will be the same as in Test Example 1, the sterilized gauze with a side of 5 mm over time while changing the sampling location from the upper gingival part that is not easily affected by saliva And measured according to a conventional method (Waps method). The results are shown in Table 11.
The number of bacteria before gargle was expressed as 100. Also, ♂ indicates a man and ♀ indicates a woman.

  From the results shown in Table 11, the number of bacteria attached to the gingiva was less than 5% even after 6 hours later than the recovery of bacteria present in saliva. Considering this data and the data of Example 1, it was estimated that it would take almost a whole day to reach the number of bacteria before gargle on the mucous membrane.

<Test Example 3>
Although the lip is not a mucous membrane, it is hardly affected by saliva. Therefore, the gargle water produced in Production Example 5 was applied to the lip, and the change of bacteria on the lip was examined.
The number of bacteria attached to the left half of the upper lip before application was measured and applied, and the number of bacteria attached to the right half of the upper lip after 4 hours, the left half of the lower lip after 8 hours, and the right half of the lower lip after 12 hours Measured. In the meantime, the meal was stopped by sucking a jelly-like nutritional food (Otsuka Pharmaceutical Co., Ltd., “Energen” (registered trademark)) with a straw to eliminate the influence from the outside as much as possible.
The results are shown in Table 12.

  From the results shown in Table 12, it was almost aseptic for about 10 hours regardless of the lips that were constantly exposed to many floating bacteria in the environment. It is speculated that the effect lasts for a long time because it can be coated on the lip surface with gargle water and not washed off with saliva.

<Test Example 4>
10 people who were bothered by bad breath were gargleed with gargle water produced by various production methods, 20 seconds 3 times (1 minute in total) twice / day for 1 week. The meal was free to eat except for odorous foods (garlic, garlic, etc.).
Breathe into the smell bag (2L) made of polyester material with high odorlessness every morning when you get up (before brushing your teeth), seal it with a silicone jar, and increase and decrease the bad breath and perform a sensory test on the properties with three odor-sensitive monitors It was. A part of the results are shown in Table 13.
In addition, the intensity of the odor sensation is displayed by a 6-step method. 0 ... Odorless 1 ... Slightly odor is finally felt 2 ... Smell that can be easily felt (the nature of odor can be imagined)
3 ... Clearly odor 4 ... Strong odor 5 ... Unusable odor

In addition, as an unpleasant indication method: 0 ... Neither pleasant nor uncomfortable -1 ... Slightly uncomfortable -2 ... Uncomfortable -3 ... Very uncomfortable -4 ... Extremely uncomfortable

As can be seen from Table 13, even if the person had a very strong halitosis, by using this gargling water, the odor was drastically reduced and almost no odor was caused by continuing gargle for 5-7 days. Originally, the person with weak smell became almost odorless after 1-2 days.
The discomfort that expresses the nature of the odor diminishes or disappears more quickly, and even those who still feel a little smell no longer have any discomfort.

<Test Example 5>
(1) Eight cases of periodontal disease that are difficult to treat (both have deep periodontal pockets) are treated with gargle water produced in Production Example 3 twice a day for only 2 months in the oral cavity for 2 months Continued.
In all cases, Poryphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans, which have high periodontal pathogenicity, were present, and the gingiva was swollen to some extent, and halitosis was strong and tooth wobble was observed.
The treatment results of three representative examples are shown in Table 14.

The clinical trial shown in Table 14 reflected that this gargle was effective as a support for the treatment of periodontal disease. Deeply in the periodontal pocket, it gradually decreased due to periodontal pathogens lingering in the alveolar pus leakage, and was almost undetectable after 2 months.
Although the opening of the periodontal pocket was not much changed, the gums were raised and the color tone returned to pink to red after 2 months, and all strong bad breath disappeared.
K. In Mr. T, the wobble of the teeth disappeared, and even hard peanuts were bitten.
If we continue to gargle as it is, some patients achieved a therapeutic result sufficient to hope that they would achieve complete healing without special treatment.

(2) Five people who had caries and had a blackish brown color were gargled twice a day with gargle water produced in Production Example 7 for several months. progress stops, strange to both reduce pain, darkening received the illusion as if it had healed tooth decay if at first glance whether to gradually deposits lime if it is lightly made C ₁ about tooth decay Continuing than two months.
In the case of C ₃ where the tooth decay was deep, the symptom was not changed with a slight decrease in color tone.

<Test Example 6>
Five patients suffering from chronic sinusitis were rinsed once daily with gargle water produced in Production Example 6 for 3 months. As a result of diagnosis based on subjective symptoms and pathological findings, all of the five patients showed relief of symptoms from about 2 weeks later, and two months later, this was confirmed by pathological examination and X-ray examination. Four months later, 3 out of 5 people were reported to be completely cured.

<Test Example 7>
Three people who were swollen or sore due to inflammation of the stomatitis or throat were rinsed twice a day with the gargle water of Production Example 2.
In any case, these unpleasant symptoms disappeared after 3 days at the longest after 1-2 days. This was similar to the case of taking a general anti-inflammatory enzyme.

<Test Example 8>
1 ml of H1N1 influenza virus solution cultured in SPF sperm eggs was diluted with 1000 ml of water.
Immediately after gargleing with the gargle water produced in Production Example 4 and after 1 hour, every 7 hours thereafter, the virus dilution was sprayed into the throat by spraying for 1 to 1.5 seconds into the throat. Neither suffered from influenza.

  Of the approximately 100 people who were gargleing with the gargle water prepared in each production example (no vaccine was administered yet), no one suffered from influenza. (Normally 5-6% morbidity)

Since the start of modern medicine, the field of medical care has been centered on therapeutic medicine, and preventive medicine has been disregarded. However, in Japan, which has entered an aging society both in name and reality, the practice of “preventive medicine” and “alternative medicine” has become more important for the suppression of medical costs while it has become enormous. The idea has been accepted and permeated and settled.
Except for so-called lifestyle-related diseases such as heart disease and diabetes, the proportion of infectious diseases is large, and most of the pathogens are established by invading through the respiratory tract and mouth. In order to prevent this, there is no doubt that correct knowledge about infectious diseases, hygienic environment and daily hand washing and gargle practice are the basic lines.
Aside from hand washing, traditional gargles are ad hoc and excessive gargles only damage the throat and promote infection.
The gargle water of the present invention is an improvement in convenience that eliminates these drawbacks, and its use will be unlimited unless the infectious disease is extinct from the earth.
For example, even in Japan, a country with advanced public health, 10 million people are infected with flu every year, and in 2009, a new swine-derived flu is rampant, especially among young people. In addition, gargle with this gargle water is simple and easy to defend and contain pandemic (global epidemic: estimated 100 million dead) due to mutation of highly pathogenic avian influenza virus (H1N5 type), which is also said to be a problem of time. The utility value is also high in that it can be made inexpensively.

  Although the invention has been shown and described in detail with reference to preferred embodiments thereof, various changes in form and detail depart from the scope of the invention as encompassed by the appended claims. Rather, it will be understood by those skilled in the art that it can be done herein.

Claims (16)

  An antibacterial disinfectant for oral cavity, comprising a metal ion having antibacterial activity, L-cysteine, L-ascorbic acid, a non-ionic surfactant, a thickener and an astringent. Metal ions having antibacterial action include trivalent iron ions (Fe ³⁺ ), II-valent iron ions (Fe ²⁺ ), zinc ions (Zn ²⁺ ), copper ions (Cu ²⁺ ), cobalt ions (Co ² ). ^The bactericidal disinfectant for oral cavity according to claim 1, which is one or more selected from the group consisting of ⁺ ), nickel ions (Ni ²⁺ ) and silver ions (Ag ⁺ ).   The concentration of antibacterial metal ions is 50 to 200 ppm for III-valent iron ions, 110 to 400 ppm for II-valent iron ions, 7.5 to 125 ppm for zinc ions, 15 to 60 ppm for copper ions, and 180 for cobalt ions. The bactericidal disinfectant for oral cavity according to claim 2, which is -300 ppm, 85-175 ppm for nickel ions, and 1-3 ppm for silver ions.   The bactericidal disinfectant for oral cavity according to any one of claims 1 to 3, wherein the concentration of L-cysteine is 100 to 1000 ppm and the concentration of L-ascorbic acid is 100 to 500 ppm.   Surfactants other than nonionics are alkylbenzene sulfonate, linear alkylbenzene sulfonate, polyoxyethylene alkyl ether sulfate, higher alcohol sulfate ester, sodium lauryl sulfate, sodium lauroyl sarcosine, stearyldimethylbenzene ammonium chloride, The bactericidal disinfectant for oral cavity according to any one of claims 1 to 4, which is one or more selected from the group consisting of benzalkonium chloride, benzethonium chloride, alkyldiaminoethylglycine chloride and alkylpolyaminoethylglycine hydrochloride. .   The bactericidal disinfectant for oral cavity according to any one of claims 1 to 5, wherein the concentration of the surfactant excluding nonionic is 20 to 100 ppm.   The bactericidal disinfectant for oral cavity according to any one of claims 1 to 6, wherein the thickener is one or more selected from the group consisting of corn starch, agar, sodium alginate, chondroitin sulfate and hyaluronic acid.   The concentration of the thickener is 20,000 to 35000 ppm for corn starch, 1000 to 1500 ppm for agar, 5000 to 8000 ppm for sodium alginate, 8000 to 15000 ppm for chondroitin sulfate, and 3000 to 5000 ppm for hyaluronic acid when added alone. The bactericidal disinfectant for oral cavity described in 1.   The astringent agent is alums, catechins, bitterns or hop extract, The bactericidal disinfectant for oral cavity according to any one of claims 1 to 8.   10. The bactericidal disinfectant for oral cavity according to claim 9, wherein the concentration of the astringent is 8000 to 12000 ppm for alums, 5000 to 10000 ppm for catechins, 8000 to 20000 ppm for bitterns, and 10,000 to 15000 ppm for hop extract.   The bactericidal disinfectant for oral cavity according to any one of claims 1 to 10, further comprising one or more selected from the group consisting of sorbic acid, sorbate, benzoic acid, benzoate and paraoxybenzoate.   The disinfectant for oral cavity according to claim 11, wherein the total concentration of sorbic acid, sorbate, benzoic acid, benzoate and paraoxin benzoate is 50 to 100 ppm.   The bactericidal disinfectant for oral cavity according to any one of claims 1 to 12, further comprising one or more selected from the group consisting of 5 to 10 ppm sialic acid, 10 to 20 ppm protein and 100 to 200 ppm herbal extract or essential oil.   The herb extract or essential oil is one or more selected from the group consisting of eucalyptus, mint, chamomile, lavender, oregano, glove, rosemary, thyme, neroli, pine, bergamot, cedarwood, hinokitiol, and tea tree oil. Item 13. A bactericidal antiseptic solution for oral cavity according to item 13.   The bactericidal disinfectant for oral cavity according to any one of claims 1 to 14, wherein the pH is adjusted within a range of 2.5 to 4.0.   The bactericidal disinfectant for oral cavity according to any one of claims 1 to 15, which has a relative viscosity of 1.5 to 2.2 when the viscosity of tap water is 1 as measured by an Ostwald relative viscometer.