Q & A
Q.What are the characteristics of lactic acid bacterium bacteriocin?
Lactic acid bacterium is one of the bacteria that has been deeply related to human life since ancient times, and is a generic term for bacteria that ferment sugar and produce a large amount of lactic acid.
Although this lactic acid bacterium is widely distributed in nature, it is especially found in fermented foods that are familiar to us, and contributes not only to improving its flavor and palatability but also to its preservability. ..
Examples include yogurt, cheese, pickles, which are fermented mainly with lactic acid bacteria, and traditional brewed foods such as sake, miso and soy sauce.
In addition, lactic acid bacteria enhance the shelf life of foods by performing lactic acid fermentation. This is because lactic acid bacteria make lactic acid and various antibacterial substances in foods.
One of them is an antibacterial peptide (protein) called bacteriocin, which is attracting attention as a safe antibacterial material.
The characteristics of bacteriocin derived from lactic acid bacteria are as follows.
1) Heat and acid resistance
2) As soon as it enters the body, it is decomposed into amino acids and is safe.
3) Instant sterilization at ultra-low concentration (1/1 billion, ppb level) compared to general antibacterial agents and antibiotics
4) Resistant bacteria are less likely to occur
5) Kill multidrug-resistant bacteria such as MRSA and VRE
6) Kill only harmful bacteria of interest
7) Tasteless and odorless
Q.What are the characteristics of lactobacillus bacteriocin "Nisin A"?
In the laboratory of Professor Kenji Sonomoto, Department of Life Sciences, Faculty of Agriculture, Kyushu University, we have been conducting various joint research with local companies, focusing on antibacterial peptides (proteins) made by highly safe lactic acid bacteria that we have eaten since ancient times. It was.
As one of the achievements, we have succeeded in the practical application (formulation) of the world-famous bacteriocin "high-purity nisin A".
Nisin is a small protein (34-amino acid peptide) produced by lactic acid bacteria (Lactococcus lactis).
It mainly shows antibacterial activity against bacteria that are closely related to lactic acid bacteria that make nisin (gram-positive bacteria).
Its antibacterial mechanism kills the bacteria of interest by puncturing the cell membrane.
This nisin has three analogs (“Nisin A”, “Nisin Z”, and “Nisin Q”). The first discovery was Nisin A, which was made by lactic acid bacteria isolated from fermented milk in 1928.
Commercialization was first sold in 1953 by a British company with the "Nisin A" formulation.
After that, the safety was recognized by the international organization WHO/FAO in 1969 and by the US FDA in 1988.
As a result, Nisin A has come to be used as a safe food preservative in more than 50 countries around the world.
Even in Japan, after being deliberated by the Ministry of Health, Labor and Welfare and the Food Safety Commission in 2009, all the genotoxicity tests, carcinogenicity tests, and other tests have been cleared, and they have been recognized as safe foods.
Furthermore, among the many lactic acid bacteria bacteriocin (antibacterial peptide), the biggest and only feature that only Nisin A has is safety.
Various lactic acid bacteriocins (antibacterial peptides) have been discovered all over the world, but as a result of GRAS certification by WHO and other health organizations in the world and the FDA in the United States, the study by Japan's Ministry of Health, Labor and Welfare regarding their safety, they were approved for food. "Nisin A" is the only lactic acid bacterium bacteriocin (antimicrobial peptide), and other lactic acid bacterium antimicrobial peptides are unapproved substances.
Among the antibacterial peptides, only Nisin A has the characteristic that the safety to the human body is guaranteed.
Q.What is "Nisin A" produced by lactic acid bacteria living in "Tofu" in Japan?
The lactic acid bacterium used in the laboratory of Professor Kenji Sonomoto is a lactic acid bacterium (Lactococcus lactis) found in the tofu “Okara” from Fukuoka Prefecture, and has the highest ability to make “Nisin A” among lactic acid bacteria in the world. It is a lactic acid bacterium.
By purifying this excellent lactic acid bacterium fermentation broth, the stable “high-purity Nisin A” used in “Neonisin-e®” can be made.
Q.What is "High Purity Nisin A"?
Fermented liquids of general lactic acid bacteria (supernatant liquid of yogurt, whey, etc.) have low stability and are easy to decompose, and also have a lot of salt and become cloudy and odorous.
"Nisin A" is also produced by a salting out method in which a large amount of salt is added to the fermentation liquid of lactic acid bacteria to precipitate the protein.
Therefore, it contains a large amount of proteins and salts other than "Nisin A" , and there is concern that it may affect the taste, which was not desirable for use as an oral hygiene agent.
The fermentation liquor is like salty and cloudy miso soup, and because "Nisin A" contains a lot of protein and salt, its use is limited to natural preservatives for foods such as ham, sausage, and cheese that use salt. Was being done.
If "Nisin A" is used in an amount that can be expected to be effective as an oral care formulation, it will have a strong odor and a salty taste.
In order to overcome this weakness, we have focused our efforts on the development of our original separation and purification technology, aiming for “Nisin A” of a quality (taste, odor, stability) that you will not notice if you put it in your mouth as it is, and research and development for 10 years Through these efforts, we have developed "high-purity and transparent", "salt-free and tasteless and odorless", "liquid and highly soluble and highly stable", and highly purified "high-purity Nisin A".
This is a unique technology that does not exist in the world. "High purity and transparent", "Salt-free and tasteless and odorless", "Liquid and excellent in solubility and high stability", "High purity Nisin A" is the only one in the world. It will be a formulation.
Q.What is "Neonisin-e®"?
"High-purity Nisin A" has been confirmed to show a strong antibacterial effect against gram-positive bacteria such as pathogenic Staphylococcus aureus and dental caries.
However, it has weaknesses such as no bactericidal effect against gram-negative bacteria such as Escherichia coli and periodontal disease-causing bacteria, and Candida and fungi.
Therefore, we selected "plum extract" and "Damask rose essential oil" derived from plants through selection tests of various natural substances.
It is said that antimicrobial substances derived from plants such as "Japanese plum extract" and "Damask rose essential oil" have antibacterial properties since ancient times.
However, since it requires a certain concentration, it has a strong taste that is not suitable for oral use. At concentrations that do not affect taste, antibacterial effects will not be exhibited.
As such, it is a substance that does not show antibacterial effects against Gram-negative bacteria and Candida bacteria alone.
As a result of repeated research, we have found the minimum necessary blending ratio of plant extract that has the antibacterial effect of "high-purity nisin A" against gram-negative bacteria and Candida.
The natural antibacterial agent with this unique blending ratio is "Neonisin-e®", and we have formulated it as a new oral antibacterial agent that has little effect on taste and taste against gram-negative bacteria and candida bacteria that have not been effective until now. Did.
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“Neonisin-e®” is a 100% natural antibacterial agent that has the effect of reducing pathogenic bacteria in the oral cavity, but even if it is ingested by accident, it is quickly decomposed into amino acids by digestive enzymes in the body, which makes it safe. It has a great advantage.
This is also the case when it is released into the environment, and because it is biodegraded into amino acids in the soil, it circulates as one of the nutrient substances in the biological ecosystem, and it can be said that it is a gentle antibacterial agent in harmony with the environment.
"Neonisin-e®" is a new age natural antibacterial agent that is safe to drink and has an instant bactericidal effect against tooth decay, periodontal disease bacteria, and Candida. And it is expected to be effectively used all over the world.
Q.What are the features of "Neonisin-e®"?
The main features are as follows.
Produced from the fungus found in Japanese tofu, an edible plant-derived food.
Instantly sterilize a wide range of trouble-causing bacteria in the oral cavity with ultra-low concentration.
If swallowed, it is safe because it is digested and decomposed as an amino acid in the intestinal tract.
If it is vomited, it is rapidly biodegraded in nature.
It is an antibacterial agent in a new era that is both human and earth friendly.
Q.What is the difference between "Neonisin-e®" and synthetic germicides and disinfectants?
The major differences are as follows.
"Compared with synthetic bactericides/disinfectants/antibiotics, it sterilizes at ultra-low concentration",
"If swallowed, it will be digested and decomposed."
"The bactericidal action has no side effects"
Conventional petroleum-derived synthetic bactericides also sterilize bacteria in the oral cavity, but if they are swallowed accidentally, they are unlikely to decompose, so they sterilize even the bacteria that work well in the intestinal tract, and There is a problem of breaking it.
In addition, because it is difficult to biodegrade even when it is exhaled, there was a problem to protect the microorganisms in the environment and the natural environment.
Many petroleum-based synthetic fungicides are industrially made from gas oil.
Due to side effects, it is regulated to 0.01 g or less in 100 g, anaphylactic shock is expressed and contraindication for use on mucous membranes other than the oral cavity, transfer to fetus or milk is reported, and long-term use for women is avoided There are things that we must have, such as organic chlorine compounds that are not found in nature and that can be converted to dioxins in a low-temperature incinerator.
Any medicine can be used, does a good job, and can be harmful.
Synthetic fungicides made from petroleum and chemical raw materials have excellent antibacterial properties, but side effects due to overdose and cases of accidental swallowing may occur, infants and elderly people who are not good at gargling and vomiting, people with disabilities, There was a problem in using pets and pregnant women who do not want to take chemically synthesized ingredients.
Alcohol (ethanol) is not recommended for infants, those who have a dry mouth, those who have a delicate mouth, those who have a rough mouth, allergies, and those who do not want to take alcohol.
As for disinfectants, hypochlorous acid is unstable and difficult to store, and strong stimulants such as chlorine, phenol and cresol are suitable for cleaning and sterilizing medical instruments, desks, floors, etc. The application for sterilizing bacteria inside and on the skin has a problem in continuous use on the human body because of the side effect of rough skin and breaking of the skin barrier.
In order to meet the needs of such people around the world, our research team has spent over 10 years researching and developing new antibacterial agents that are both effective and safe for the human body.
"Neonisin-e®" is a natural antibacterial agent made from antibacterial peptides (protein/bacteriocin) made by lactic acid bacteria and edible plant ingredients.
Its mechanism of action is to adsorb on the recognition site (lipid II) of the cell membrane of the target bacterium and instantly open a hole to kill the bacterium. After finishing its role of antibacterial property, it rapidly biodegrades as an amino acid.
Even if it is accidentally swallowed, it is decomposed and digested in the digestive organs, so it is kind to the stomach and body, and when it is exhaled, it is rapidly biodegraded, which is also kind to the global environment.
The biggest difference is immediate effect on target bacteria, safety on human body, and environmental friendliness.
Q.What is the difference between "Neonisin-e®" and plant antibacterial agents?
The major differences are as follows.
"Disinfect at ultra-low concentrations compared to plant antibacterial agents"
"If swallowed, it will be digested and decomposed."
"The bactericidal action has no side effects"
Until now, antibacterial agents made from plants had to be concentrated in order to exert their bactericidal effect, and there was always the problem of side effects.
Although plant-derived antibacterial agents sterilize bacteria in the oral cavity, they also have the side effect of sterilizing bacteria that work well in the intestinal tract and destroying the stomach.
Also, in the race for survival in the history of the earth, the toxicity of plants as a counter force against living organisms, that is, the counter force against bacteria (antibacterial property), can be used to exterminate only bacteria.
However, when a plant-derived antibacterial agent is used for human beings, which are living organisms, bacteria exist in the intestinal tract and skin and cannot be separated, so in order to eliminate bad bacteria, the good parts of the human body are also damaged. There are problems such as genetic side effects such as death, killing bacteria that work well in the body, burdening internal organs to detoxify and decompose in the body, and giving birth to malformed children.
"Neonisin-e®" has been proven by health institutions around the world that "it shows high antibacterial activity at extremely low concentrations", "decomposition when swallowed", and "no side effects". You can say the difference.
Plant-derived antibacterial agents include essential oils obtained by distilling plants in order to increase the concentration of plant extracts, and extracts and resins obtained by concentrated extraction.
For the long time since the birth of the earth, plants that animals do not like to eat have evolved the toxicity of being inedible in order to survive in the survival competition with animals, insects, microorganisms and molds that eat themselves. ..
Taking advantage of the toxicity of these plants, human beings have been used for medicine since ancient times as herbs and herbal medicines that are boiled or concentrated to enhance their effects. The medicinal properties contained in plants that have been used as medicines are gradually being elucidated in modern science, but not all are elucidated.
Although plant-derived antibacterial substances bring beneficial effects depending on the amount and method of use, there are issues regarding the amount and concentration at which clinical effects can be expected and the safety to the body.
For example, in Japan, there is a tree called cypress, which has been used for the pillars of homes, rice bowls, and bath tubs because of its antibacterial and antiseptic properties.
Japanese cypress has evolved to be toxic for protection in a hot and humid forest like Japan because it is not attacked by microorganisms, bacteria, molds and insects.
A small amount of hinokitiol, a substance obtained from the tree extract, is useful for termite repellent and rice preservation, but when concentrated and concentrated to a level that has a bactericidal effect on living things such as bacteria, malformation in rat experiments The risk of babies (teratogenic side effects) has been reported.
Therefore, there are problems in using it for pregnant women, infants, girls and women.
Concerning tea that is safe to drink, catechin, which is its ingredient, may be concentrated and concentrated to cause liver dysfunction, according to the Canadian Health Organization.
In short, the toxicity of plants can kill organisms that are organisms, but at the same time can harm humans that are organisms. This action/reaction is similar to the effect of anti-cancer drugs on cancer cells and the resulting damage to healthy cells.
Any medicine can be used, it works well, and it is harmful, but if the concentration is increased and the target bacteria are sterilized, the side effects will be stronger.
At the same time, it has been a difficult task to achieve both a stimulus and taste that humans and animals can put in the mouth and a stimulus and scent that can be applied to the skin at high concentrations.
Furthermore, sap-based hinokitiol, etc. has the strength of peeling off plastic tubes, which poses packaging issues, elderly people requiring nursing care who are unable to gargle or vomit, and who are suffering from illness or who have disabilities. There is anxiety about changes in condition due to use on the oral cavity and skin and burden on internal organs.
Our research team has also been researching and developing new antibacterial agents that are both effective and safe for the human body, including Japanese hinokitiol and tea catechin, as well as the world's herbs, mastic, and Asian herbal medicine, which have been reported in the past. We have spent more than 10 years researching ourselves in order to effectively utilize plant extracts, plant antibacterial agents, and animal antibacterial agents produced by plants such as propolis.
Since these plant antibacterial agents are non-patentable ingredients, we can easily utilize them for research and development and products.
However, although the drug is used in quantity, in the experiment in a petri dish, a plant-based antibacterial agent that can exterminate the target bacterium is also actually used clinically in the human body at a concentration that exterminates the target bacterium. If you choose to do so, the side effects will inevitably increase, and there were many difficulties in researching and developing products that you really want your family to use.
And over 10 years, we repeated the comparison of antibacterial activity in the classification of plant antibacterial agents all over the world, measurement of antibacterial activity by synergistic effect with lactic acid bacteria antibacterial peptide, evaluation of clinical effect and safety, etc. As a result, we arrived at the most effective and safe invention of "Neonisin-e®".
Its mechanism of action is to adsorb on the recognition site (lipid II) of the cell membrane of the target bacterium and instantly open a hole to kill the bacterium. After finishing its role of antibacterial property, it rapidly biodegrades as an amino acid.
In addition, it is also of great benefit to human beings that it exhibits high antibacterial activity at extremely low concentrations (one billionth of a ppb level) compared to general antibacterial agents and antibiotics.
Given that the bactericidal effect of the tea antibacterial agent tea catechin is 1, "Neonisin-e®" has a bactericidal activity several thousand times that of tea catechin and hinokitiol. In other words, the same bactericidal effect can be achieved at an ultra-low concentration of several thousandths.
"Neonisin-e®" was discovered by British people about 100 years ago from the cheese that humans have eaten for thousands of years, and the repeated dose toxicity at WHO and other health organizations in developed countries, as well as Japan's Ministry of Health, Labor and Welfare, Carcinogenicity, reproductive toxicity, genotoxicity, and other safety-tested low-concentration Nisin A used in foods in over 50 countries,
It is made from trace amounts of edible plants, such as plums that people have eaten since ancient times, and whose safety has been established for edible use and skin.
The biggest difference is immediate effect on target bacteria and safety on human body.
Q.What is the difference between "Neonisin-e®" and "lactic acid bacteria"?
The big difference is "immediate effect" and "safety".
Unlike lactic acid bacteria, "Nisin A" has the following characteristics.
1) Heat and acid resistance
(Lactic acid bacteria themselves are weak to heat and acid)
2) Instantly sterilize at extremely low concentration (1/1 billion, ppb level) compared to general antibacterial agents and antibiotics
(Lactic acid bacteria themselves do not have bactericidal power)
3) Less resistant bacteria
(Lactic acid bacteria themselves have no immediate effect)
4) Kills multi-drug resistant bacteria such as MRSA and VRE
(Lactic acid bacteria themselves do not have bactericidal power)
5) Kill only harmful bacteria of interest
(Lactic acid bacteria themselves do not have bactericidal power)
6) Tasteless and odorless
(Lactic acid bacteria have odor and taste)
This research project in Japan has been conducting research on lactic acid bacteria antibacterial substances (human, animal, insect, plant-derived) collected from all over the world for over 20 years.
Kenji Sonomoto, Professor Emeritus at the Faculty of Agriculture, Kyushu University, has discovered more than 20 kinds of novel lactic acid bacteria antibacterial substances (bacteriocins), and is the world's leading researcher with the highest number of discoveries in the world.
Dr. Sonomoto has screened the antibacterial properties, evaluated the efficacy, and evaluated the safety of hundreds of lactic acid bacteria collected from all over the world.
However, it was verified that none of the lactic acid bacteria antibacterial substances collected from all over the world for 20 years can have antibacterial activity higher than that of "Nisin".
And there is a fact that other universities, companies, and research institutes all over the world have not yet been able to find an antibacterial peptide having a bactericidal activity that exceeds "Nisin" discovered about 100 years ago.
In other words, it can be said that "Nisin" had a strong antibacterial activity that could be discovered even with the technology and knowledge about 100 years ago, and it is thought that substances beyond that may not exist on Earth.
In terms of safety, cheese has been used by humankind for thousands of years, and has more safety than Nisin, which was discovered about 100 years ago and has been researched and evaluated by WHO and other health institutions around the world. The antibacterial peptide to be obtained does not exist, and even if it is discovered, it will take decades more to verify its efficacy and safety before it is useful to humankind.
Based on the above, we believe that the following is useful.
Further research into “Nisin”, which was discovered about 100 years ago and proved to be safe in the world and has a strong bactericidal power, will contribute to the development of humankind who face difficulties.
There are many foods and cosmetics in the world that contain lactic acid bacteria themselves.
It can be said that products that appeal to the usefulness of lactic acid bacteria, especially antibacterial properties, are products that anticipate the effects of antibacterial substances, that is, antibacterial peptides.
Lactic acid bacteria are edible, and in terms of safety appeal, it gives a very good image as an antibacterial product containing lactic acid bacteria.
And even today, various lactic acid bacteria are discovered all over the world every year.
The lactic acid bacterium that produces "Nisin" is called "Lactococcus lactis".
There are many types of "Lactococcus lactis bacteria", and the one used for "neonisin-e®" is "Nisin" discovered in 2002 by Professor Kenji Sonomoto of Kyushu University. It is a special lactic acid bacterium strain that stably produces a large amount.
And you can also make yogurt, drinks, foods, oral care products, and skin cosmetics that contain this live Lactococcus lactis.
In addition, if the lactic acid bacterium-containing product is a lactic acid bacterium that acts alive, it is possible to increase it by using yogurt at home.
However, products containing lactic acid bacteria for oral care and skin use have the following major problems.
Living lactic acid bacteria (probiotics) do not have antibacterial properties themselves, but exert their antibacterial properties by producing antibacterial substances such as hydrogen peroxide, aldehydes, and lactic acid bacteria antibacterial peptides (bacteriocin).
However, there are four major hurdles in actually exerting an antibacterial effect in the oral cavity where about 700 kinds of bacteria live up to 1 trillion.
The first hurdle is that it is difficult to establish lactic acid bacteria in the oral cavity.
In fact, it's easily washed away by saliva, drinks and toothpaste.
Also, as in the case of intestinal bacteria, lactic acid bacteria ingested from commercially available yogurt etc. are also excreted from the body within a few days in the intense competition for survival of many types of intestinal bacteria that already live, and actually enter the intestines. Just as it is difficult to settle in, it has been difficult for bacteria to settle into the oral cavity from the outside.
The second hurdle is that lactic acid bacteria cannot be expected to be clinically immediate and have a bactericidal effect.
Even if the ingested lactic acid bacteria could be established among the bacteria resident in the oral cavity, the production of antibacterial substances is unknown because lactic acid bacteria are easily affected by the oral environment. In addition, it takes tens of minutes or more before the antibacterial effect is produced.
In addition, a large amount of lactic acid bacteria is required to affect the indigenous bacteria in the oral cavity that exceed the maximum of 1 trillion ingested lactic acid bacteria.
However, how much the number of lactic acid bacteria contained in an oral care product used at one time can affect has actually been a clinical issue.
In addition, it was difficult to eat a large amount of yogurt or to ingest lactic acid bacteria.
In addition, the fact that a large amount of lactic acid bacteria and yogurt are contained in the oral cavity leads to the side effect of corroding teeth.
In other words, it had to be washed off with saliva, drink, toothpaste, etc., and there was a problem with the clinical effect.
The third hurdle is that lactic acid bacteria die when used as a product, and a bactericidal effect cannot be expected.
Live lactic acid bacteria will rot at room temperature, so synthetic preservatives (paraben, also known as paraoxybenzoic acid, sodium benzoate, sorbic acid K) are used for oral care products such as toothpaste and mouthwash, and cosmetics for the skin. , Phenoxyethanol, phytic acid, etc.), alcohol (ethanol), plant essential oils must be added. In addition, synthetic bactericides (CPC, also known as cetylpyridinium chloride, etc.), sodium hydrogen carbonate (baking soda/alkali), and soap (alkali) may be added.
If so, the bacteria will die, no antibacterial substances can be expected to be produced from the dead bacteria, and the combination of lactic acid bacteria will be meaningless.
Dead bacteria that have died due to preservatives and heat-treated dead bacteria do not work in the oral cavity because they are dead.
In the intestine, there are reports that dead bacteria may feed enterobacteria, but the action of dead bacteria in the oral cavity has not been globally proven, and there was a problem.
And the fourth and final hurdle is that safety to the human body has not been proven.
If there is experimental data that has a bactericidal effect on live lactic acid bacteria or dead lactic acid bacteria (killed bacteria that have been sterilized by heat treatment, etc.), the bacteria will produce ・Hydrogen peroxide produced, aldehydes, antimicrobial peptides (bacteriocin), etc. The presence of antibacterial substances may be considered.
It has a bactericidal action, but hydrogen peroxide and aldehydes produced by lactic acid bacteria may affect the human body.
In addition, if the antibacterial effect is some kind of lactic acid bacteria antibacterial peptide (bacteriocin), there was a new issue.
About 100 kinds of lactic acid bacterium antibacterial peptide (bacteriocin) have been found in the world including human, animal and insect origins, but verification of cytotoxicity, repeated dose toxicity, carcinogenicity, reproductive development toxicity, genotoxicity, etc. This is because only Nisin A is the only food additive approved in Japan as WHO.
Other novel lactic acid bacteria antibacterial peptide (bacteriocin) is derived from lactic acid bacteria, but it is an unapproved substance without safety information that has not been verified/established and may be accidentally swallowed. There was a problem in using infants who are not good at exhaling, elderly people, people with disabilities, pets, pregnant women who do not want to take chemically synthesized ingredients, etc.
Many of the newly discovered lactic acid bacteria antibacterial peptides (bacteriocins) have not been reported to have side effects, but this is because the global research has not progressed and the risks have not been clarified.
Based on the above, the use of lactic acid bacteria per se in oral care products and cosmetics for skin has been a challenge for expected factors.
"Neonisin-e®" has overcome these four hurdles.
"Neonisin-e®" is used in foods in more than 50 countries around the world after having been verified by WHO and other health institutions in developed countries that produce plant-derived lactic acid bacteria, and has been approved by the Japanese Ministry of Health, Labor and Welfare. This is a natural antibacterial agent with higher activity after separating and purifying "Nisin A", a lactic acid bacterium antibacterial peptide (bacteriocin), from bacteria and combining it with trace amounts of edible plant components.
Its mechanism of action is to adsorb on the recognition site (lipid II) of the cell membrane of the target bacterium and instantly open a hole to kill the bacterium. After finishing its role of antibacterial property, it rapidly biodegrades as an amino acid.
Compared with general antibacterial agents and antibiotics, it shows high antibacterial activity even at extremely low concentrations (one billionth of a ppb level), and even with a small amount, a very high bactericidal effect can be obtained. It has unprecedented benefits to humanity.
The biggest difference is immediate effect on target bacteria, safety on human body, and high effect in a small amount.
Q.What is the difference between "Neonisin-e®" and other "lactic acid culture extract"?
The labeling of "Neonisin-e®" is "Lactic acid bacteria culture extract", "Plum fruit extract", and "Damask rose oil".
This is because "Neonisin-e®" is a mixture of the above ingredients.
Ordinary "lactic acid bacterium culture extract" is a liquid obtained by fermenting lactic acid bacteria, and in many cases, it is like the supernatant of yogurt.
And many things such as water, impurities, and salt are turbid in the fermented liquid.
On the other hand, "Lactobacillus culture extract" used in "Neonisin-e®" is very different from other fermentation liquors, and only the antibacterial peptide "Nisin A" produced by lactic acid bacterium is unique from the fermentation liquor fermented with lactic acid bacterium. It will be isolated and highly purified by biotechnology.
It is "highly purified Nisin A" as a highly pure lactic acid bacterium antimicrobial peptide liquid, which can take out only about one-tenth of the amount from ordinary lactic acid bacterium culture liquid, which requires more than 10 times the manufacturing cost and labor.
Highly purified "Nisin A" has a 100 times or more difference in the purity, degree of purification, stability and effect from the fermentation liquid of normal lactic acid bacteria.
The patented ingredient "Neonisin-e®", which has been researched and developed through industry-academia collaboration with Kyushu University etc., has the same name as other "lactic acid bacterium culture extract" in terms of ingredient display, but the actual dimension is completely different.
Q.What is the origin of the lactic acid bacteria used for the production of "Neonisin-e®"?
Even if you say "lactic acid bacteria" that you can eat, their habitat and origin are various.
Even if you say "lactic acid bacteria" with a good image, it will be completely different depending on the bacterial species and strain.
There are also lactic acid bacteria derived from the ground, rivers, insects and animals, and humans. There are also lactic acid bacteria that live in the intestinal tract (feces) and excrement of animals, and in blister and sludge.
There are also lactic acid bacteria found in plaque accumulated in the mouth of people who cannot brush their teeth but have caries or periodontal disease, and lactic acid bacteria found in the feces and dirt of other people.
Actually, the strains of adult feces and dental plaque are often stronger than the bacteria of feces and dental plaque of infants and children, and bacteria isolated from human feces and dental plaque of adults are used. The reality is that there are many cases.
However, yogurt, beverages and oral products made by fermenting other people's feces and dental plaque bacteria do not want to put it in ourselves, families, children and patients' mouths and do not apply it to the skin. There is a big problem.
Regarding the antibacterial peptide (bacteriocin) that may be mixed in the "fermented products" of the bacteria derived from feces and dental plaque, there is a possibility that the habitat of the bacteria may be effective against miscellaneous bacteria. Antibacterial peptides (bacteriocin) other than “A” are unapproved substances that have not been verified for safety by WHO, the world health organizations, or the Japanese Ministry of Health, Labor and Welfare.
"Lactococcus lactis" used in the production of "Neonisin-e®" is a lactic acid bacterium found in Japanese tofu, a clean and safe food of plant origin.
And for decades, a lactic acid bacterium that inhabits plant-derived foods that mass-produces lactobacillus antibacterial peptide "Nisin A", which has been licensed around the world. It is a research result.
The lactic acid bacteria used in "Neonisin-e®" are clean and safe lactic acid bacteria found in edible plant-derived foods, so you can safely put them in your mouth.
For the type and origin of lactic acid bacteria that you put in your mouth, we recommend that you check the name of each bacterium on the Internet.
Q.Does "Neonisin-e®" use "lactic acid bacteria derived from animals (humans, livestock, etc.) (bacteria that live in feces of humans and animals)"?
Not used at all.
As mentioned above, this point is due to the background of long and deep research including the world's leading researcher of lactic acid bacteriocin research that can be applied to food at the Faculty of Agriculture of Kyushu University. Will be.
"Neonisin-e®" is a "put it in your mouth" formulation.
Not "animal-derived fungus" that lives in "excretion" in the intestinal tract of "animal", which is found from human or animal feces, etc.
We use "Lactococcus lactis", which is a "plant-derived fungus" that lives in "food" found in Japanese "tofu".
For the type and origin of lactic acid bacteria that you put in your mouth, we recommend that you check the name of each bacterium on the Internet.
Q.Is "Nisin A" different from "Neonisin-e®"?
The major differences are as follows.
Sterilize "Gram-negative bacteria" and "Candida bacteria",
"High stability" and "tasteless and odorless"
About 100 years ago, it was discovered in cheese in the United Kingdom, "Nisin", which has been used as a safe preservative in foods in 50 countries all over the world, is a "gram positive bacterium" (caustic bacteria in the mouth, etc.). Only) has a bactericidal effect, and there is a problem that periodontal bacteria, aspiration pneumonia-causing bacteria, "gram-negative bacteria" that cause bad breath, and "candida (yeast/fungus)" do not sterilize.
The importance of toothbrushing has spread through the educational efforts of dentists and dental hygienists, and the prevalence of tooth decay has decreased, while periodontal disease, aspiration pneumonia, oral candida, etc. have increased as the population ages. There was a need for antibacterial agents that comprehensively sterilize the bacteria that cause problems in the oral cavity, "Gram-positive bacteria," "Gram-negative bacteria," and "Candida bacteria."
And general “Nisin” has low stability and is easily decomposed, and it also has a lot of salt and becomes cloudy and odorous. Since it is like miso soup that is salty and cloudy, its use was limited to natural preservatives for foods such as ham, sausage, and cheese that use salt.
If Nisin is used in an amount that can be expected to be effective as an oral care preparation, it will have a strong odor and a salty taste.
In the case of small additions that do not affect the taste, that is, products with "Nisin" that is not salty and has no odor will actually be meaningless.
“Neonisin-e®” has overcome this weakness.
Through collaboration with industry, academia and government, we have focused our efforts on the development of our original separation and purification technology, aiming for "Nisin A" of the quality (taste, odor, stability) that you will not notice if you put it in your mouth, and after 10 years of research and development Developed "Nisin A", "high purity and transparent", "salt-free and tasteless and odorless", "liquid and highly soluble and highly stable", and highly purified.
This is a unique technology not found in the world. "Highly pure and transparent", "Salt-free and tasteless and odorless", "Liquid and highly soluble and highly stable", "Highly purified Nisin A" are the only formulations in the world.
Furthermore, by combining the problems of "Nisin", which until now had only a bactericidal effect only with "Gram-positive bacteria", in combination with edible plant extracts at a unique mixing ratio, an antibacterial spectrum against "Gram-negative bacteria" and "Candida bacteria" Expand.
Overcoming the weaknesses of "Nisin" up to now, we have invented and patented "Neonisin-e®", which is ideal as a natural antibacterial agent.
And in 2013, it became the world's first to open the way to the healthcare application of lactic acid bacteria antibacterial peptide (bacteriocin).
Although "Nisin" and "Neonisin-e®" have similar notations, they were actually different inventions.
Q.Does "Neonisin-e®" disinfect the virus?
It does not disinfect.
Bacteria and viruses are different.
Bacteria are small organisms. It is called a unicellular organism because it has only one cell.
Bacteria can grow by replicating the same bacteria as you have, as long as you have a nutrient source. There are also harmful bacteria that enter the human body and cause illness. On the other hand, there are bacteria that are useful for human life. There are many kinds of bacteria in the human body, which maintain the environment from the mouth to the skin surface and intestines.
Escherichia coli, Staphylococcus aureus, and Mycobacterium tuberculosis are known as bacteria that can cause human diseases. Antibacterial agents (antibiotics, antibiotics) are drugs for combating bacteria.
Viruses, on the other hand, are about one-fifth the size of bacteria, very small, and do not have their own cells. Viruses have no cells, so they live by getting into other cells. When a virus invades the human body, it enters the human cell to make a copy of itself, and the cell ruptures, causing a lot of virus to fly out and enter other cells. In this way, the virus propagates.
Influenza virus, norovirus, coronavirus, etc. are known as viruses that can cause diseases in humans.
Since viruses are different in size and mechanism from bacteria, antibacterial agents (antibiotics, antibiotics) do not work.
Only a small number of antiviral drugs have been developed in the world.
Similarly, "Neonisin-e®" is effective against bacteria but cannot disinfect viruses.
However, a virus cannot exist alone, and it will always increase with bacteria such as unicellular organisms as hosts. Therefore, suppressing the reproduction of host bacteria also helps prevent infection.
With the influenza virus, it enters the respiratory tract through the nose and mouth with breathing and contact.
However, it seems that little is known that oral health is associated with more severe influenza virus infections.
The bacteria in the mouth excrete enzymes such as protease and neuraminidase as their metabolites. Proteases destroy proteins, and in a dirty state, viruses are more likely to enter through weak areas of the mucous membrane. In particular, the more severe the periodontal disease, the greater the tissue damage and the more likely it is to suffer.
Antiviral drugs such as Tamiflu and Relenza do not act directly on the virus, but suppress the action of proteases and neuraminidase, and prevent the spread of infection by trapping the influenza virus in the cells.
And "Neonisin-e®" instantly kills oral bacteria that produce enzymes such as protease and neuraminidase.
In addition, since the effects of Tamiflu and Relenza become worse when there are a lot of bacteria, oral care to suppress the growth of oral bacteria and to keep the mouth clean is important in order to speed up healing if affected.
According to the Japan Dental Association, thorough oral care has reported that the incidence of influenza has dropped dramatically by a factor of 10.
There are two routes of influenza virus transmission: “spray infection” and “contact infection”.
It is important to improve your immunity, and at the same time clean your nose breathing to prevent invasion, masks for going out, washing hands when you return, mouthwash, oral care, etc.
*We are confirming the new coronavirus as it is an unknown virus.
Q.Does "Neonisin-e®" make resistant bacteria?
It does not make resistant bacteria.
There are no research reports of the emergence of resistant strains of "Nisin" in the research institutes in developed countries, including the United Kingdom, which discovered "Nisin" in cheese about 100 years ago.
"Nisin", a protein and bacteriocin produced by lactic acid bacteria, is different from antibiotics that act over time because it has a characteristic of immediate action on bacteria (it takes time for bacteria to develop resistance), and it gives bacteria time. It has the feature that it does not make resistant bacteria.
Q.What is the negative effect of "Neonisin-e®" on the human body?
“Nisin” is a protein naturally contained in traditional fermented foods such as yogurt, cheese, and rice bran picked, and is a food that humans have eaten since ancient times.
Discovered in cheese in the United Kingdom in 1928 due to advances in science, “Nisin” was approved by WHO and FAO in 1969, and generally certified as safe (GRAS) in the United States in 1988. As a natural antibacterial agent that is safe for the human body by any of the absorption methods, it has been approved for use in more than 50 countries including developed countries.
In the United Kingdom, France, etc., the amount of licensed cheese is unlimited, and in Japan, after the deliberation by the Ministry of Health, Labor and Welfare and the Food Safety Commission in 2009, genotoxicity tests, carcinogenicity tests, and other tests are also conducted. All cleared and recognized as safe food.
For reference, the GRAS (generally recognized as safe) judgment that evaluates the safety of food is as follows.
The US Food and Drug Administration (FDA) provides data on food additives to prove that they are scientifically evaluated for human safety and the rigorous safety standard “logical certainty of being harmless”. Based on the above verification, GRAS (generally recognized as safe), that is, generally accepted as safe, is determined.
"Nisin" has undergone various verifications in 1988, and has received the GRAS judgment, like "salt", "vinegar", "spices", "spices" and "soy sauce".
You can also refer to the “Nisin” evaluation data provided by the Japanese Ministry of Health, Labor and Welfare.
Ministry of Health, Labor and Welfare Japan Food Safety Commission Additives Special Survey Committee
August 2007 Nisin Evaluation Report
https://www.mhlw.go.jp/shingi/2007/10/dl/s1024-15d.pdf
Q.Does "Neonisin-e®" also destroy human cells?
Do not break.
In research and safety verification by research institutes around the world, it has been proved that "Nisin A" kills only bacteria and does not destroy eukaryotic cells (human cells).
Due to its characteristics, it is expected to be used around the world for disinfecting healing wounds, pressure ulcers, and inflammation in the mouth.
Q.Is "Neonisin-e®" incompatible with inflammation and wounds?
Because it sterilizes only bacteria and does not destroy eukaryotic cells (human cells), I think that it is good for healing stomatitis, scratches, skin sores, and skin troubles.
Q.Porphyromonas glaae is a periodontal pathogen in dogs. Is "Neonisin-e®" sterilized?
"Neonisin-e®" sterilizes bacteria belonging to Gram-positive bacteria, Gram-negative bacteria, and Candida bacteria in the same manner.
Porphyromonas glaae is also a gram-negative bacterium of the same genus as Porphyromonas gingivalis, so sterilize it in the same way.
For the bactericidal effect against individual bacteria, please check the attributes of the bacteria.
Q.Can lactic acid bacteria "itself" kill Gram-negative bacteria and fungi?
The mechanism by which lactic acid bacteria (“Gram-positive bacteria”) make antibacterial peptides (bacteriocins) and kill other bacteria is to suppress the killing of similar bacteria (“Gram-positive bacteria”) in the competition for survival between bacteria. , That is, that they proliferate and survive.
And lactic acid bacteria have a self-tolerance mechanism so that they do not die by the bacteriocin they made.
Therefore, lactic acid bacteria can sterilize "Gram-positive bacteria" similar to themselves, but sterilize "Gram-negative bacteria" and "fungi/Candida bacteria" with completely different structures that have an outer membrane outside the cell wall. There was a problem that I could not do it.
Can lactic acid bacteria "itself" kill Gram-negative bacteria and fungi?
The mechanism by which lactic acid bacteria (“Gram-positive bacteria”) make antibacterial peptides (bacteriocins) and kill other bacteria is to suppress the killing of similar bacteria (“Gram-positive bacteria”) in the competition for survival between bacteria. , That is, that they proliferate and survive.
And lactic acid bacteria have a self-tolerance mechanism so that they do not die by the bacteriocin they made.
Therefore, lactic acid bacteria can sterilize "Gram-positive bacteria" similar to themselves, but sterilize "Gram-negative bacteria" and "fungi/Candida bacteria" with completely different structures that have an outer membrane outside the cell wall. There was a problem that I could not do it.
"Neonisin-e®" has overcome this hurdle.
We have expanded the antibacterial spectrum of bacteriocin, which was previously limited to only "Gram-positive bacteria", to "Gram-negative bacteria" and "Candida bacteria" by a new invention.
Overcoming the weaknesses of lactic acid bacteria and lactic acid bacteria antibacterial peptides up to now, we have achieved the invention and patent of "Neonisin-e®", which is ideal as a natural antibacterial agent.
Q.What are the expectations for "Neonisin-e®" in oral hygiene?
There are about 700 microbial species that parasitize the body, of which about 500 are present in the oral cavity.
Bacteria present in the oral cavity are called oral bacteria, and there are 100 million bacteria per ml in saliva.
Most of oral bacteria are so-called "non-pathogenic bacteria" that are harmless to the human body, but some of them are called "pathogenic bacteria" that cause dental caries (cavities), periodontal disease-causing bacteria, and yellow grapes. There are bacteria such as cocci and microorganisms such as Candida which is a type of mold.
However, there are usually only a few such pathogenic bacteria, so there is no problem.
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However, if you do not brush your teeth, bacteria will adhere to the tooth surface and multiply, creating large lumps of bacteria formed from various bacterial species.
This is the so-called dental plaque. The formation of dental plaque leads to the development of caries (cavities) and periodontal disease.
Dental caries is a disease that causes defects in teeth, and periodontal disease is a disease that destroys the tissues that support teeth, but both are bacterial infections.
Therefore, it is important to prevent the formation of dental plaque to prevent dental caries and periodontal disease.
In addition, recently, it has been reported and reported that such an oral disease affects or even causes the whole body.
For example, periodontal disease is originally a disease of periodontal tissues, but arteriosclerosis, diabetes, and effects on the fetus have been pointed out.
Therefore, the idea that oral health is related to general health is rapidly spreading.
There are a large number of bacteria in the oral cavity, and these bacteria co-exist and antagonize each other to form the human-specific bacterial flora.
Bacteriocin is a general term for antibacterial substances produced by bacteria, and a great many bacterial species produce their own bacteriocin.
By producing bacteriocin, bacteria suppress the growth of other bacteria and try to secure a place for their own growth.
Nisin A used in "Neonisin-e®︎" is a bacteriocin produced by lactic acid bacteria, but it is attracting attention as an extremely safe antibacterial substance.
To prevent dental illnesses such as dental caries and periodontal disease, it is important to thoroughly brush your teeth and encourage so-called "plaque control" without creating dental plaque.
However, it is difficult to brush the teeth firmly, and it is very difficult for the bedridden elderly and people with disabilities to brush their teeth.
In such cases, you can expect efficient plaque control by using an antiseptic-containing mouthwash.
However, many mouth rinses currently on the market are not good for drinking, and their use is limited. The antibacterial agent "Neonisin-e®" of the present invention, which is safe to drink, is considered to be a caries and periodontal disease preventive agent that can be widely used with great confidence.
In addition, "Neonisin-e®" is an important bacterium for the formation of dental plaque, and it has been clarified that it exerts a strong antibacterial activity against mutans streptococci known as a cariogenic bacterium.
Eliminating this mutans bacterium suppresses the formation of dental plaque, leading to the prevention of caries and periodontal disease.
Q.Does "Neonisin-e®" control only bad bacteria and increase only good bacteria?
The following are known in modern science:
1. Not able/cannot classify all human indigenous bacteria as good or bad.
2. There is no technology that can classify the same creature as good or evil and kill or make use of only one.
It is said that about 500 kinds of bacteria, including those that have not yet been named, live in our oral cavity up to 1 trillion.
In modern modern science, the identification of bacteria that cause tooth decay and periodontal disease among the resident bacteria in the oral cavity is progressing.
In fact, it is not possible to separate all the good bacteria and bad bacteria in the oral cavity including those that have no name.
In the oral cavity, even good bacteria, which are considered to be good bacteria, may have a bad effect in some situations (also called opportunistic bacteria),
On the contrary, it is not possible to scientifically deny that the indigenous bacteria, which are said to be bad for causing tooth decay and periodontal disease, also have a good function of suppressing bacterial invasion from the outside.
In other words, there is no evidence and no details have been researched or elucidated regarding the judgment of good or bad of indigenous bacteria.
Next, bacteria are classified as Gram-positive bacteria, Gram-negative bacteria, fungi, etc., and are not classified as good bacteria or bad bacteria.
The point is that there is no state-of-the-art technology to separate and sterilize the same organisms as good and bad.
The following are the current findings in the world's most advanced lactic acid bacteria research, that is, research on probiotics and lactic acid bacteria antibacterial peptides (bacteriocins).
The antibacterial substances and antibacterial peptides (bacteriocins) produced by lactic acid bacteria vary depending on the type, but there are many antibacterial spectra (range) to wide.
For example, “Nisin A”, one of the ingredients of “Neonisin-e®”, which was first discovered and most famous in the world, has the broadest antibacterial spectrum among lactic acid bacteriocins and kills most of Gram-positive bacteria. I will.
On the other hand, bacteriocin, which has a narrow antibacterial spectrum, kills only certain Gram-positive bacteria (Gram-positive bacteria closely related to the production bacteria).
It can be said that this is "a certain bacterium or bacteriocin selects and kills certain bad bacteria", but unfortunately it also kills the closely related Gram-positive bacteria to eliminate them completely. I will let you.
Among the closely related bacteria of Gram-positive bacteria, Streptococcus mutans bacteria that cause bad tooth decay and select "only" and "single sterilization" bacteria, substances and bacteriocins are still found in the world. not.
In other words, the latest technology cannot "sterilize by selecting only bad bacteria" and "increase only good bacteria" in the oral cavity.
We human beings are the same as the living things on the earth, but each of them supports each other, complements each other, acts and lives, and coexists in balance.
All living things on earth do not exist insignificantly, and in the situation where their functions and interactions are not elucidated in science, it is impossible to distinguish everything from good and evil, and it cannot be distinguished from superior and inferior Is the fact.
In addition, even in the same human being, it has been reported that the composition of salivary bacteria varies depending on ethnicity, family, and individual, depending on heredity and living environment. For each person, more than several hundred types of oral bacteria are good or bad. It cannot be said that the bacteria cannot be separated.
The bacteria and flora that we have in the oral cavity, skin, and intestines are not those that we have from birth, but the bacteria and flora that we inherit from our parents, and the most suitable bacteria for each individual protect our bodies. ..
Like human beings, creatures have good and bad sides for certain people and societies, but they are born and exist because they are needed, and live and coexist with their individual characteristics.
Invisible to the eye, it is the same for the same organism, bacteria.
The oral cavity suffers from trouble because it is one of the Gram-positive bacteria, Cariestobacilli, that lives in the mouth as an indigenous bacterium and does not normally cause any problems (useful for some reason). Produce acid from food waste and sugar as food to cause dental caries, and that periodontal disease bacteria, which are one of the Gram-negative bacteria, “excessively increase” between the teeth to form biofilms and cause inflammation of the gums. The cause is that it becomes dirty and the total number of bacteria “excessively increases” and flows into the lungs.
"Neonisin-e®" helps to keep the oral cavity healthy and peaceful by approaching the trouble-causing bacteria that are present as oral resident bacteria and cause "too many" problems.
For details, please see the paper.
※"Oral candidiasis"
Oral candidiasis is an infection caused by an opportunistic infection of Candida, which is a resident bacterium in the oral cavity. Onset of milky white mossy spots on the mucous membranes is caused by some underlying diseases, systemic factors such as weakly resistant infants and the elderly, who are being treated with immunosuppressants and antibacterial drugs. The treatment of oral Candida has usually involved oral care and the use of antifungal agents, powerful synthetic fungicides that kill mold. However, oral care alone cannot sterilize and cure oral Candida once it develops, and the use of antifungal drugs has the problem of resistant bacteria and side effects (stomach etc.), so it is safe and effective even if swallowed. There has been a worldwide demand for new therapeutic agents with high levels of efficacy.