JP5434915B2 - Helicobacter pylori disinfectant - Google Patents

Description

The present invention is infected fixing the gastric mucosa and gastric mucus, proliferate and progresses from chronic gastritis gastric, duodenal ulcers, furthermore is relates to pesticides of Helicobacter pylori bacteria also trigger the gastric (Helicobacter pylori).

  Epidemiological investigations revealed that Helicobacter pylori chronic gastric mucosal infection is responsible for gastric cancer, stomach, and duodenal ulcer, and its removal and sterilization are recommended from both the prevention and treatment viewpoints. Yes.

  The bacterium was first isolated and discovered in human gastric mucosa in 1982. It is said that 70% of Japanese people over the age of 40 are infected and are now recognized as a national illness. It is a Gram-negative spiral gonococcus with extremely multi-flagellate flagells that lives mainly in close contact with the surface layer of the gastric mucosal epithelial cells and its intercellular spaces, and its pathogenic agent (chronic active gastritis) is a strong urease of this bacterium. It is presumed to be due to active oxygen produced from neutrophils infiltrating the gastric mucosa lamina propria by toxins such as ammonia and cytotoxin produced by activity.

As a result of persistent infection, the gastric mucosa gradually becomes old and thins, and then progresses to atrophic gastritis, which eventually becomes an ulcer, and further develops an refractory and highly recurrent ulcer that destroys the stomach wall. It is said that the cells eventually become cancerous and turn into gastric cancer.
In fact, 94% of gastric cancer patients were infected with high frequency from the gastric mucosa of the pyloric antrum in patients with stomach and duodenal ulcers, and the World Trade Organization (WHO) certified H. pylori as a reliable carcinogen. doing.

The above is similar to the case of hepatitis C, where hepatitis C virus (HCV) shifts from hepatitis to cirrhosis by engulfing hepatocytes over a long period of time and eventually leads to liver cancer.
For the examination of H. pylori, (1) a method of directly collecting stomach tissue using an endoscope and examining it by microscopic observation and culture; and (2) collecting exhaled breath before and after taking ¹³ C-labeled urea. However, there are several testing methods, such as a method for examining the presence or absence of H. pylori from the ratio of carbon dioxide contained therein, and (3) a method for examining the presence or absence of antibodies in blood or urine. The breath test is recommended for its rapid and high sensitivity, and the present inventors have also adopted it for the test.

At present, in order to sterilize Helicobacter pylori, various combinations of drugs, mainly antibiotics, have been tried. In Europe and the United States, bismuth preparations, triple combination therapy using metronidazole and antibacterial agents, and dual combination therapy using a combination of acid secretion inhibitor proton pump inhibitor and amoxicillin are the mainstream. Recently, therapies using prounothol, sofalcone and amoxicillin have also been carried out, but sufficient sterilization rates have not been obtained with any of these therapies. In addition, side effects such as diarrhea are a concern depending on the administration of antibiotics, and if sterilization fails, the risk of the emergence of resistant bacteria has begun to be pointed out (Patent Document 1).
For example, the current mainstream of disinfection and sterilization methods are two types of antibacterial agents (amoxicillin and clarithromycin) and gastric acid secretion inhibitor (PPI) taken twice a day for 7 consecutive days. Although it is about 80%, there are many cases where it is difficult to sterilize due to the emergence of drug resistant strains recently. Successful eradication improves tissue inflammation, reduces recurrence of ulcers, and reduces the risk of developing gastric cancer.

On the other hand, there are reports that the administration of special lactic acid bacteria and daily intake of antibacterial foods such as plum pickles are effective as methods that do not rely on drugs, but there are many experts who question the effectiveness with unknowns. .
Japanese Patent Laid-Open No. 11-189529 (paragraph 0004)

The present invention has been made in view of the above circumstances, and provides a Helicobacter pylori disinfectant excellent in safety that can be killed in a short time and substantially based on a concept that has not existed in the past. With the goal.
Further, the present invention, when used together with conventional antibiotics, the pesticides of Helicobacter pylori with excellent safety disinfection can allowed to substantially kill at a Helicobacter pylori carriers difficult with conventional The purpose is to provide.

  As a result of intensive studies on a disinfectant that can be sterilized by almost 100% even in cases where the conventional method does not lead to sterilization, and the method, the present inventors lurk inside and outside the gastric mucosa covered with gastric mucus. The present invention was completed by succeeding in killing H. pylori earlier and completely.

That is, the gist of the present invention is as follows.
[1] A metal ion having antibacterial action, L-cysteine, and L-ascorbic acid as main components, and a surfactant excluding nonionics as a main component ,
The metal ions having antibacterial action are (III) -valent iron ions (Fe ³⁺ ), (II) -valent iron ions (Fe ²⁺ ), zinc ions (Zn ²⁺ ), copper ions (Cu ²⁺ ), One or more selected from the group consisting of cobalt ions (Co ²⁺ ), nickel ions (Ni ²⁺ ) and silver ions (Ag ⁺ ),
Surfactants other than the nonionic are alkylbenzene sulfonate, polyoxyethylene alkyl ether sulfate, higher alcohol sulfate ester, sodium lauryl sulfate, sodium lauroyl sarcosine, benzalkonium chloride, benzethonium chloride and alkyldiaminoethylglycine hydrochloride One or more selected from the group consisting of:
A Helicobacter pylori disinfectant , wherein the concentration of L-cysteine is 25 to 250 ppm and the concentration of L-ascorbic acid is 20 to 100 ppm ,
[ 2 ] The concentration of metal ions having antibacterial activity is 30 to 100 ppm for (III) -valent iron ions, 50 to 250 ppm for (II) -valent iron ions, 5 to 10 ppm for zinc ions, 10 to 25 ppm for copper ions, The Helicobacter pylori disinfectant according to [ 1 ], wherein cobalt ion is 50 to 180 ppm, nickel ion is 40 to 85 ppm, and silver ion is 0.5 to 1 ppm ,
[ 3 ] The Helicobacter pylori disinfectant according to [1] or [2] , wherein the concentration of the surfactant excluding nonionic is 5 to 10 ppm,
[ 4 ] In any one of [1] to [ 3 ], further containing at least one selected from the group consisting of sorbic acid, sorbate, benzoic acid, benzoate, and paraoxybenzoate The described Helicobacter pylori disinfectant,
[ 5 ] The Helicobacter pylori disinfectant according to [ 4 ] above, wherein the concentration of sorbic acid, sorbate, benzoic acid, benzoate, and paraoxybenzoate is 10 to 20 ppm,
[ 6 ] The Helicobacter pylori disinfectant according to any one of [1] to [ 5 ], wherein PH is adjusted to 2.5 to 4.0,
[7] above [1] Ri consists Helicobacter pylori pesticides and antibiotics according to any one of to [6],
The antibiotic is a Helicobacter pylori disinfectant comprising three agents of amoxicillin, clarithromycin and a proton pump inhibitor ,
About.

  Today, “safety and safety” is the most important aspect in all fields, and health and medical care are no exception. It is said that the number of adult diseases (lifestyle-related diseases) and chronic infections due to the arrival of an aging society and the accompanying increase in medical expenses are inevitable, and in the developed countries, it will be markedly 60 million. This drug can contribute to the prevention and treatment of stomach, duodenal ulcer and gastric cancer caused by chronic infection with Helicobacter pylori. Once disinfection / sterilization is successful, the possibility of recurrence is almost zero. Furthermore, if used in combination with the current 3 mainstream of sterilization for several days, the success rate is almost 100% and side effects caused by long-term administration of antibiotics (diarrhea, allergy, hemorrhagic colitis, taste disorders, etc.) There is no expression of.

  The Helicobacter pylori disinfectant of the present invention is characterized in that it contains a metal ion having antibacterial action, L-cysteine and L-ascorbic acid as main components and a surfactant excluding a nonionic system.

(1) Metal ions having antibacterial action The metal ions having antibacterial action include (III) -valent iron ion (Fe ³⁺ ), (II) -valent iron ion (Fe ²⁺ ), zinc ion (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 Helicobacter pylori disinfectant of the present invention may be adjusted as appropriate so as to obtain a desired bactericidal power. For example, in the case of (III) -valent iron ions, 30 to 100 ppm, (II ) 50-250 ppm for valent iron ions, 5-10 ppm for zinc ions, 10-25 ppm for copper ions, 50-180 ppm for cobalt ions, 40-85 ppm for nickel ions and 0.5-1 ppm for silver ions. preferable.

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 / disinfecting solution of the present invention is preferably 20 to 250 ppm.

(3) L-ascorbic acid The action of L-ascorbic acid is as described above. The content of L-ascorbic acid in the Helicobacter pylori disinfectant of the present invention is preferably 20 to 100 ppm.

(4) Surfactants excluding nonionic surfactants The basic structure of surfactants consists of lipophilic groups that are familiar with oil and hydrophilic groups that are compatible with water, and its action is wet, moisture absorption, penetration, solubility, emulsification, dispersion, Wide range of foaming, lubrication, washing, antistatic, adsorption, film formation, antibacterial, cell membrane disturbance, rust prevention, etc. Synthetic detergents, kitchen detergents, toothpastes, rinses, emulsifiers, softeners, etc., are completely incorporated into our daily lives and are now recognized as essential.
Many surfactants have the above-mentioned effects, but as a surfactant excluding nonionics that can be used in the present invention in view of the viewpoint and aim of "sterilization and disinfection". Include the following anionic surfactants, cationic 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.

  Among these, surfactants other than nonionics are alkylbenzene sulfonate, straight bell alkyl benzene sulfonate, polyoxyethylene alkyl ether sulfate, higher alcohol sulfate, sodium lauryl sulfate, sodium lauroyl sarcosine, stearyl dimethylbenzene chloride. One or more selected from the group consisting of ammonium, benzalkonium chloride, benzethonium chloride, alkyldiaminoethylglycine hydrochloride and alkylpolyaminoethylglycine hydrochloride are preferred.

  The concentration of the surfactant excluding the nonionic system is preferably 5 to 10 ppm in the Helicobacter pylori fungicide.

(5) Others The Helicobacter pylori disinfectant 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.
The concentration of the sorbic acid, potassium sorbate, benzoic acid, sodium benzoate, and paraoxybenzoic acid esters in the Helicobacter pylori disinfectant is preferably 10 to 20 ppm.

  The Helicobacter pylori disinfectant of the present invention can be prepared by adding and mixing the various components to 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.

(6) pH
Moreover, in the Helicobacter pylori disinfectant of the present invention, by adjusting the acidity, it contributes to the maintenance and stability of the titer of the constituents of the Helicobacter pylori disinfectant and at the same time supports the penetration into the pathogen. The pH of the Helicobacter pylori disinfectant of the present invention is preferably 2.5 to 4.0. A known pH adjuster can be used for adjusting the pH.

  In addition, the Helicobacter pylori disinfectant of the present invention, when used in combination with antibiotics, makes it possible to disinfect even Helicobacter pylori with antibiotic resistance that was difficult to achieve with antibiotics alone. Exterminating effect.

  Examples of the antibiotic include amoxicillin, clarithromycin, and a proton pump inhibitor. Examples of the proton pump inhibitor include rampsolazole, omeprazole and the like. These antibiotics may be used alone or in combination of two or more. Especially, it is preferable to use together 3 types, amoxicillin, clarithromycin, and a proton pump inhibitor.

  The mechanism of action of the Helicobacter pylori disinfectant of the present invention is complex and not yet fully elucidated, but the antibacterial action of metal ions caused by cell membrane damage and destruction due to surface tension reduction (the center of the mechanism is strong oxidation) Active oxygen production by ion catalysis, generation of hydrogen peroxide by ion reduction, destruction of the cell itself by generation of OH radicals, coagulation and denaturation of proteins, disturbing enzyme system and inhibiting metabolic function Furthermore, it is assumed that it exhibits the ability of killing in a very short time by maximizing the effect of linking to bacterial -SH group, -COOH group, -OH group, etc. Yes.

  The Helicobacter pylori disinfectant of the present invention can be sterilized and exterminated by being taken into the stomach and brought into contact with Helicobacter pylori.

  As a method for delivering the Helicobacter pylori disinfectant into the stomach, the disinfectant can be used as it is or by drinking the disinfectant with other liquid components.

  Among these, as a method for controlling Helicobacter pylori, the killing effect can be enhanced by administering 75 ml or more of the Helicobacter pylori control agent.

  Further, the eradication effect can be enhanced by continuously administering the Helicobacter pylori eradication agent for 4 to 5 days.

  Hereinafter, specific production examples and examples will be described, but the gist of the present invention is not limited thereto.

Hereinafter, the development of the present invention will be described in order.
First of all, we started with a textbook of successful treatment methods that do not rely on surgical operations for chronic infections that have been difficult for the past.
One example is skin ringworm, which is caused by parasitosis in the stratum corneum on the surface of the skin, and when the protein (keratin) in the stratum corneum is propagated as a nutrient source, In the past, there was no choice but to apply drugs from the outside, but nowadays, imidazole antifungal drugs with relatively little toxicity are used for several months depending on the symptoms and combined with conventional external drugs. It is coming mainly. That is, it became possible to almost completely cure the stubborn athlete's foot which was said to be incurable by attacking ringworm fungus from inside and outside.
In chronic sinusitis (pyremic syndrome), antibiotics (many macrolides) are administered for 3 to 6 months as internal medicines, and external detergents (steroids, antibiotics, mucolytic agents, vasoconstriction) The patient was relieved from suffering by treating it with a small amount of a drug, etc., attached to the nasal mucosa as a nepriser.
Even in cases of hemorrhoids, especially internal hemorrhoids, relieving is quick by using oral medication and suppositories or ointments.
Furthermore, even in the case of chronic cutaneous candidiasis (superficial candidiasis), it has become possible to eliminate stubborn Candida by externally using an imidazole antifungal agent and a triazole internal medicine in combination.
Although it is not an infectious disease, it can be resolved quickly by improving systemic symptoms from the inside and roughening cream for rough skin. It is a place that we often experience in daily life that we can accomplish our objectives by acting simultaneously from inside and outside, not just disease. When attacking a castle from ancient times, it is similar to not only attacking from the outside, but also making it possible to quickly fall down even with a small amount of force by working on it to lead to collapse from the inside.
These facts indicate that when the lesion is located under the skin or submucosa, it is essential to attack the lesion simultaneously from inside and outside, not to administer the drug only from the outside or only from the inside, in order to achieve perfection and early treatment. It is suggested that.
The present inventors have adopted this phenomenon and actual situation for the elimination of Helicobacter pylori. For some reason, anatomically, the stomach and intestinal lumen are directly connected to the outside world, so the above treatment method can be applied from the idea and logic that "the stomach mucosa is an inverted body surface" It is because it was judged that.

[1] Destroying from the outside, sterilization (1) First, it was decided to verify the antibacterial activity of an in vitro test, although it was said to be effective against H. pylori. 2% by weight of a H. pylori suspension (1 × 10 ⁸ cells / ml) is added to an aqueous solution to which 10% of each food or plant extract is added, and the fungus is fished over time. Planting and culturing in an environment containing 5% carbon dioxide were observed for the damage of the fungus and its bactericidal effect.
The contact time was up to 5 minutes in consideration of the time spent in the stomach when ingested and acting on H. pylori.
Medium composition: (Skirow medium)
Proteose peptone 15g
Liver digestion powder 2.5g
Yeast extract 5g
NaCl 5g
Horse defibrinated blood 5ml
The results are shown in Table 1 below.

  As is clear from the above results, it was not adversary to kill H. pylori by contact for 5 minutes, but it could be confirmed that it did not cause any damage to H. pylori except for cocoa. Experimental contact for 30 minutes was also attempted, but the result was basically the same as the result in 5 minutes, but did not die.

Next, in a similar test, 1 × 10 ⁷ cells / ml of medium was inoculated into Shirorow medium supplemented with 10% of the above-mentioned extract sterilized with a filter, and the presence or absence of its growth was observed. ── (Setting that is in contact with the extract during the culture period)
Table 2 shows the results in a simplified manner.

The addition of 10% of the extract to the medium showed antibacterial action, but the action was growth-inhibiting or bacteriostatic, and did not show bactericidal effect as in the results in Table 1.
Broccoli sprouts, chamomile, scallops, mint, licorice, etc. showed similar results. In addition, a combination test of each extract was also attempted, but no additive or synergistic effect was observed, and it was obvious that it could not contribute greatly to the elimination and sterilization of Helicobacter pylori hidden inside and outside the gastric mucosa. In other words, it was unavoidable if it was ingested over a long period of time, and it was unavoidable if it was ingested for a short period of time.
Thus, only so-called sterilizing liquids remained in the test object.

(2) Of the existing sterilizing liquids, a sterilizing liquid which has been recently used for sterilizing foods and which is relatively safe for the human body was tested. Prepare a suspension of Helicobacter pylori (1 × 10 ⁸ cells / saline water) and add 2% by weight of the germ solution to the disinfectant solution. The bactericidal effect was observed with and without proliferation.
The results are shown in Table 3 below.

  The “strongly acidic water” is obtained by adding salt to water and electrolyzing it through a special membrane. The pH is 2.7 or less, the oxidation-reduction potential (ORP) is 1100 mV, and the residual chlorine is 20 ppm or more. It has a strong bactericidal power because it is far beyond the microbial growth environment with water. It is close to a sodium hypochlorite solution widely used as a sterilizing and disinfecting solution, and the sterilizing power is mainly brought about by a strong oxidizing action.

“Ozone water” means that oxygen (O ₂ ) is changed to ozone (O ₃ ) by passing oxygen through two electrodes sandwiched between dielectrics and discharging them by passing an alternating high voltage. It is aerated and dissolved in water. It contains about 0.1 ppm of ozone and destroys and lyses bacterial cell membranes with a strong oxidizing action.

  “Ozone nano bubble water” is a substance that gives physical stimulation to fine bubbles of ozone less than 50 μm, and dissolves them in water. It is pink and has not only a bactericidal action but also various physiological activities. It is said to be effective.

The used pesticide is called Helicobacter pylori sterilizing solution, and its composition is shown below (Production Example 1).
Production Example 1 (1000 ml)
FeCl ₃ · 6H ₂ O 0.96g
L-cysteine 1g
L-ascorbic acid 0.1g
0.05g potassium sorbate
Sodium lauryl sulfate 0.1g
3N HCl 1ml
Remaining water

  As is clear from the above table, all the bactericidal solutions were able to kill H. pylori by contact for about 10 seconds.

  Next, 10% and 20% amounts of the above-mentioned sterilizing medium were added to each of the above-mentioned sterilizing medium, and inoculated with Helicobacter pylori, and only Helicobacter pylori sterilizing liquid exerted a strong antibacterial action to inhibit the growth of Helicobacter pylori. I was killed. This is shown in Table 4.

This test result clearly demonstrates that, in the presence of organic matter, bactericidal components are rapidly decomposed or consumed in strongly acidic water, ozone water, and ozone nanobubble water, and the H. pylori bacteria can hardly be damaged. It was. That is, even if a sterilizing liquid excluding the Helicobacter pylori sterilizing liquid is sent into the stomach, it has been suggested that the effect may be rapidly reduced or invalidated by gastric mucus, food residues, and the like.
Therefore, gastric mucus is actually created artificially, and 10%, 20%, and 50% are added to each sterilizing solution. Immediately after the addition, 5 minutes, 10 minutes, and 15 minutes later, Helicobacter pylori is suspended. A turbid liquid (1 × 10 ⁸ cells / 1 ml of saline) was dropped 2% by weight and contacted, and the bactericidal effect was observed over time. The artificial gastric mucus used the composition shown in Table 5 below with reference to the US pharmacy method and the like.

  The gastric mucus is produced and secreted by the surface mucosa cells present on the surface of the gastric mucosa and the gland mucus cells on the surface of the stomach and is insolubilized in the insoluble mucus gel layer and the gastric lumen. It works as a barrier that protects the stomach with a thickness of. It is a complex mixture composed of various substances, and its main component is mucin (mostly glycoprotein consisting of carbohydrates), but it has not been fully elucidated.

  The obtained bactericidal effects are shown in Tables 6 (1) and (2). In the case of mixing after 10 minutes and 15 minutes, similar results were shown after 5 minutes of mixing, so they were omitted.

As is clear from the above results, when H. pylori is ingested immediately after mixing artificial gastric mucus, in the case of strongly acidic water, ozone water, ozone nanobubble water, the concentration of artificial gastric mucus is 10% and contact with H. pylori for 3 minutes or more. Died. In the case of Helicobacter pylori sterilization solution, it was not killed in 10 seconds, but it was killed in 30 seconds of contact.
When artificial gastric mucus was added in an amount of 20%, three species other than the Helicobacter pylori sterilizer did not die even after 5 minutes of contact, but the Helicobacter pylori sterilizer died in 1 minute.
In addition, when the amount was 50%, it was found that the three species were not killed by contact with 5 minutes but were killed by contact with Helicobacter pylori in 3 minutes.

Next, when Helicobacter pylori was added 5 minutes after mixing artificial gastric mucus, in the case of strongly acidic water, ozone water, ozone nanobubble water, gastric mucus concentration was not killed even at 10%.
On the other hand, the Helicobacter pylori sterilizing solution showed the same effect as that immediately after mixing artificial gastric mucus. That is, the mixture was killed in 10 minutes when mixed for 30 seconds and 20% when mixed for 1 minute, and mixed when mixed with 50% in 3 minutes.

  Based on the above test results, the sterilization liquid stays in the stomach for 5 minutes, and even if it is not toxic to strongly acidic water, ozone water, or ozone nanobubble water, it is administered to the stomach cavity and migrates in the mucus of the stomach. Eradication or inactivation of Helicobacter pylori and the H. pylori lurking under the mucous membranes has proven to be invincible.

  Therefore, in the future, it was decided to proceed with various experiments and tests only for the “H. As described above, the Helicobacter pylori sterilization solution has a basic substance of life activity as a main component and high mucosal affinity and cell permeability.

  Next, examples of various Helicobacter pylori sterilizing liquids produced in production other than Production Example 1 are summarized in Tables 7 (1) and (2) as Production Examples 2 to 10.

  Artificial gastric mucus was added to each Helicobacter pylori sterilization solution prepared in these production examples in 10%, 20%, 30% and 50% amounts, respectively, inoculated with Helicobacter pylori, and the death time was roughly measured. The results are shown in Table 8.

As is apparent from Table 8, in any Helicobacter pylori sterilizing solution, the addition of 10% artificial gastric mucus kills H. pylori on contact for 30 seconds to 1 minute, 20% to 1 to 2 minutes, 30% to 1 It was possible to kill in 5 minutes to 3 minutes and 50% in 3 minutes to 5 minutes.
For example, when administered (taken) in the 100 ml stomach, gastric mucus mixing is estimated to be about 20% at most during the 5-minute stay in the stomach, and therefore H. pylori can be killed within 2 minutes. It was.

  Next, Helicobacter pylori sterilization solution was diluted with water, 20% of artificial gastric mucus was added to the solution, and the concentration at which H. pylori dies within 5 minutes was investigated. This Helicobacter pylori sterilizing solution is almost harmless and non-toxic, but it is self-evident that it is easier to use if it is still effective after being diluted. The results are shown in Table 9.

  Any Helicobacter pylori sterilization solution was diluted 3 to 4 times (20% of artificial gastric mucus contained), and showed the ability to kill H. pylori within 5 minutes.

Furthermore, as a result of various tests on the necessary minimum amount of the surfactant that is most concerned among the components of Helicobacter pylori sterilizing solution, the concentration of amino acids, vitamins and minerals as main components is not significantly affected. It became clear that the concentration shows a sufficient bactericidal effect.
This is thinner than the concentration of surfactant remaining in the mouth after we brushed the mouth every day and rinsed the mouth once or twice daily and there is no problem. (By the way, general toothpaste contains about 5% of surfactant such as sodium lauryl sulfate as a detergent and foaming agent-50000ppm)

  As a result of diligently carrying out various tests including the above test, the concentration of the main component was 30 to 100 ppm for (III) -valent iron ions, 50 to 250 ppm for (II) -valent iron ions, and 5 to 10 ppm for zinc ions. 10 to 25 ppm for copper ions, 50 to 180 ppm for cobalt ions, 40 to 85 ppm for nickel ions, 0.5 to 1 ppm for silver ions, L-cysteine concentration is 25 to 250 ppm, and L-ascorbic acid concentration is 20 to 20 ppm. 100 ppm, 5 to 10 ppm of surfactant excluding nonionic, and 10 to 20 ppm is sufficient for H. pylori when sorbic acid, sorbate, benzoic acid, benzoate and paraoxybenzoate are included. I found out that I could show sterilization ability.

  The bactericidal solution produced based on the above knowledge is referred to as “Pylori colori” (registered trademark) solution in the present specification, and production examples (per 1 L) are shown in Table 10 below.

[2] Destruction and sterilization from the inside We decided to follow the combination of antibiotics and gastric acid secretion inhibitors, which are currently widely used for sterilizing H. pylori.
Applicable to health insurance is a combination of penicillin-type amoxicillin (AMPC) and macrolide-type clarithromycin (CAM), and gastric acid secretion inhibitor proton pump inhibitor (PPI) lansoprazole or omeprazole. It is said that the success rate is 80% by taking 3 drugs twice a day (morning, after dinner) for 7 days continuously, but according to one theory, 50% is divided by the appearance of resistant H. pylori Therefore, it is desirable to isolate and collect Helicobacter pylori inhabiting the gastric mucosa and conduct a susceptibility test. Based on the results, it is desirable to administer antibiotics, but basically the conventional three-drug eradication method is used. You can adopt it.
Hereinafter, examples in the production examples of the above-mentioned “H. pylori / colori solution”, examples in “3 agents”, and examples in which both are used together will be described.

<Example 1> Only "H. pylori colori solution" is administered Urea breath test (urea: ¹³ C Ubit tablet, Otsuka Pharmaceutical, carbon dioxide carbon isotope ratio analyzer, POC one, Otsuka Electronics Co., Ltd.) 10 people were given "H. pylori colori solution" once a day for 100 hours after fasting for 8 hours. After administration, they were laid on the left side of the body for 5 minutes. A method of aiming and sterilizing was adopted (continuous administration for 7 days).
The clinical trial results were judged immediately after completion of the administration and by a 1 month urea breath test. The results are shown in Table 11 (1).
As is clear from the results shown in Table 11 (1), 2 cases (20%) were successful in sterilization in 10 cases where only “H. pylori cholori solution” was administered, and 6 cases had considerable effects. Unfortunately, it was not completely sterilized, and the remaining two were less effective.
In consideration of the pre-administration test values of 2 successful eradication patients, the values of ¹³ C change are 8.5% and 7.5%, and the values are low. It was done. There were no side effects observed in all the trial subjects.

Therefore, the next 8 patients (80%) who conducted the same clinical trial of only “H. pylori colori solution” for 10 infected persons with ¹³ C change of 10% or less succeeded in complete sterilization. The results are shown in Table 11 (2).
Although the activity of Helicobacter pylori in the above-mentioned infected persons was weak, the eradication success rate was 80%, and the results were comparable to or better than the published “three-agent” internal use. There were no side effects observed in all the trial subjects.

The evaluation criteria in Tables 11 (1) and (2) are shown below.
Judgment ◎: Presumed to be completely dead
○: Although there was a considerable effect, H. pylori was gradually recovered without reaching complete death
△: Effective but not sufficiently killed by Helicobacter pylori
X: Almost no effect

<Comparative example>"Conventional 3 medications"
The existing “3 agents” were administered to 10 H. pylori infected persons according to the manual.
Specifically, three capsules of amoxicillin 250 mg, one tablet of clarithromycin 200 mg, and one capsule of lansoprazole 30 mg were taken by infected persons twice daily after morning and dinner. The clinical trial results are shown in Table 12.

As is clear from the above table, the success rate of sterilization was 60%. In addition, although the effect was recognized, 30% did not reach complete sterilization, and 10% was ineffective (it seems to be an infection with antibiotic-resistant H. pylori).
Basically, the results of trials for randomly selected infected individuals were better than the administration of “H. pylori colori solution” alone, but of course, when it was resistant, there was no effect at all.

<Example 2>
10 persons infected with Helicobacter pylori were administered 100 ml of “H. pylori cholori solution” once a day for 8 hours or more after fasting, and the existing “three drugs” were also administered according to a conventional method. Four patients who were unsuccessful in sterilization in the comparative example also participated in this trial. The results are shown in Table 13.

As is clear from the above table, the sterilization rate was 100%.
In particular, E. coli, which appeared to be infected with resistant strains. Mr. T succeeded in sterilization. It was inferred that antibiotics that were essentially ineffective acted effectively because the bacteria were weakened by "H. pylori colori solution" and changed from active to dormant.
In addition to the above 10 people, there were 50 people who participated in this clinical trial, but only 2 people were sterilized unsuccessfully, and the real success rate reached 96%. In addition, no adverse reactions were observed in all the trial subjects.

<Example 3>
Next, when “Pylori colori solution” of Production Example 1 and “3 agents” were used in combination, the relationship between the number of administration days and the sterilization rate was examined. The results are shown in Table 14.

  As is clear from the above table, 100% eradication rate was exhibited by continuous administration for 4 to 5 days. In addition, no adverse reactions were observed in all the trial subjects.

<Example 4>
Furthermore, it was decided to investigate the interrelationship between the concentration and dosage of “Pylori colori solution” in Production Example 1 and the number of administration days. When the dose is set to 25 ml, 50 ml, 75 ml and 100 ml and the concentration in the case of 100 ml is 1 (the same concentration as that administered in Examples 1 to 3), 25 ml (concentration 1, 2, 3, 4) 50 ml (concentration 1, 1.5, 2) and 75 ml (concentration 1, 1.3). An outline of the success rate of sterilization in combination with “3 agents” is shown in Table 15 below.

As is apparent from the above table, the dose of “H. pylori cholori solution” is 75 ml or more, preferably 100 ml or more. Even if the liquid volume is decreased and the concentration is increased by that amount, a sufficient effect can be obtained in vivo. Not found out.
The reason for this was that about 100 ml was necessary for the “H. pylori cholori solution” to spread throughout the stomach cavity, mainly in the gastropyloric vestibule, where H. pylori is a major habitat. . In addition, no adverse reactions were observed in all the trial subjects.
Needless to say, it is possible and optional to make the "H. pylori colori solution" fragrant or flavored with fragrance or essence to make it easy to drink.

As mentioned above, although a part of Example was introduced, let us touch on the toxicity test at the end.
The toxicity of the Helicobacter pylori sterilizing solution of the present invention prepared in Production Example 1 is 1 ml> for oral administration of LD50 in mice, 4 ml for intraperitoneal administration, and the cytotoxicity (inhibition of cell proliferation) in animal cells is the test cell (monkey kidney CV) -1 cells and human lymphocytes), but about half of the cells could proliferate without damage even when diluted 10-fold. No obstacles were observed at 1000 to 10000 dilution.
In addition, the H. pylori solution of the present invention produced in other production examples is further less toxic and proved to be an extremely safe Helicobacter pylori disinfectant.

A long time ago, tuberculosis was said to be a national illness, and tuberculosis measures such as prevention and treatment throughout the country were effective and decreased rapidly. At one time, it was said to be a past infectious disease. By use, H. pylori infection will follow the same trajectory as the tuberculosis case.
In addition, the method of use of this drug should deal with both external attacks (drugs, probiotics such as lactic acid bacteria) and internal attacks (antibiotics, vaccines, etc.) to eradicate the infectious disease-causing bacteria. It will be a guideline for future countermeasures against infectious diseases, especially treatment methods for chronic cases.

While many of the advantages of the invention encompassed herein have been described above, it will be understood that this disclosure is merely exemplary in many respects. Without departing from the scope of the present invention, various changes can be made in details, particularly in matters such as the shape, size and arrangement of parts.
Of course, the scope of the invention is limited by the language set forth in the appended claims.

Claims (7)

A metal ion having antibacterial action, L-cysteine and L-ascorbic acid as a main component, and a surfactant excluding a nonionic system in the main component ,
The metal ions having antibacterial action are (III) -valent iron ions (Fe ³⁺ ), (II) -valent iron ions (Fe ²⁺ ), zinc ions (Zn ²⁺ ), copper ions (Cu ²⁺ ), One or more selected from the group consisting of cobalt ions (Co ²⁺ ), nickel ions (Ni ²⁺ ) and silver ions (Ag ⁺ ),
Surfactants other than the nonionic are alkylbenzene sulfonate, polyoxyethylene alkyl ether sulfate, higher alcohol sulfate ester, sodium lauryl sulfate, sodium lauroyl sarcosine, benzalkonium chloride, benzethonium chloride and alkyldiaminoethylglycine hydrochloride One or more selected from the group consisting of:
The Helicobacter pylori disinfectant, wherein the concentration of L-cysteine is 25 to 250 ppm and the concentration of L-ascorbic acid is 20 to 100 ppm . The concentration of metal ions having an antibacterial action is 30 to 100 ppm for (III) -valent iron ions, 50 to 250 ppm for (II) -valent iron ions, 5 to 10 ppm for zinc ions, 10 to 25 ppm for copper ions, and 10 to 25 ppm for cobalt ions The Helicobacter pylori disinfectant according to claim 1 , which is 50 to 180 ppm, nickel ion is 40 to 85 ppm, and silver ion is 0.5 to 1 ppm . The Helicobacter pylori disinfectant according to claim 1 or 2 , wherein the concentration of the surfactant excluding the nonionic system is 5 to 10 ppm. The Helicobacter pylori control according to any one of claims 1 to 3 , further comprising at least one selected from the group consisting of sorbic acid, sorbate, benzoic acid, benzoate, and paraoxybenzoate. Agent. The Helicobacter pylori fungicides according to claim 4 , wherein the concentration of sorbic acid, sorbate, benzoic acid, benzoate, and paraoxybenzoate is 10 to 20 ppm. The Helicobacter pylori disinfectant according to any one of claims 1 to 5 , wherein the pH is adjusted to 2.5 to 4.0. Ri consists Helicobacter pylori pesticides and antibiotics according to any one of claims 1 to 6
A pesticide for Helicobacter pylori , wherein the antibiotic comprises three agents of amoxicillin, clarithromycin and a proton pump inhibitor .