JP2010163397A - Antibacterial composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an antibacterial composition which not only has excellent antibacterial properties capable of demonstrating potency against viruses but also has excellent safety to organisms such as humans. <P>SOLUTION: The composition includes at least a 6-12C fatty acid and a monoglycerin fatty acid ester. The composition has antibacterial power to annihilate Pseudomonas aeruginosa even at a concentration of 2,000 ppm or less in the antibacterial test. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an antibacterial composition having specific antibacterial properties. More specifically, the present invention relates to an antibacterial composition having not only excellent antibacterial properties capable of exerting effects against viruses such as avian influenza virus, but also excellent safety against living organisms such as humans. In the present invention, “antibacterial” has a broad meaning. That is, the antibacterial composition of the present invention can exert effects on various microorganisms such as bacteria and viruses, as will be described later.

  Infectious diseases caused by various pathogenic microorganisms (used in the present invention in a sense that also includes so-called “opportunistic infections”) are an eternal threat to mankind. Therefore, there is no doubt that such countermeasures against infectious diseases will have extremely important significance in the future. In recent years, infectious diseases caused by various viruses such as avian influenza virus have also become a new threat to mankind.

  For such infectious diseases, antibacterial drugs or antiviral drugs including antibiotics have been developed and widely used. However, such antibacterial drugs and antiviral drugs have extremely strong efficacy by themselves, but the properties of the drug itself (that is, acute, subacute, chronic toxicity, etc.) and serious drug resistance. Cause some problems.

  On the other hand, in recent years, a large-scale epidemic called pandemic has become a global problem. For such a pandemic, conventional antibacterial drugs and antiviral drugs cannot be used (for example, disinfection by drug spraying).

  For large-scale application, various drugs have been used as disclosed in Patent Documents 1 to 7 below. However, these large scale spraying agents do not have effective antiviral properties.

JP 2006-158361 A JP 2008-63304 A JP-A-9-328404 JP 2007-191480 A JP 2002-514186 A JP 2007-302587 A JP 2006-328039 A

  The object of the present invention is to solve the above-mentioned drawbacks of the prior art and to have an antibacterial composition that not only has excellent antibacterial properties that can also exert its effect on viruses, but also has excellent safety against living organisms such as humans. Is to provide.

  As a result of intensive studies, the present inventor has found that a composition containing at least two specific components and exhibiting a specific antibacterial activity against Pseudomonas aeruginosa is extremely effective in achieving the above object. .

  The antibacterial composition of the present invention is based on the above findings. More specifically, the antibacterial composition is a composition containing at least a fatty acid having 6 to 12 carbon atoms and a monoglycerin fatty acid ester; It has an antibacterial activity that kills Pseudomonas aeruginosa at the following concentrations.

  As described above, according to the present invention, there is provided an antibacterial composition not only having excellent antibacterial properties capable of exerting effects against viruses such as avian influenza virus, but also having excellent safety against living organisms such as humans. Provided.

  Hereinafter, the present invention will be described more specifically with reference to the drawings as necessary. In the following description, “parts” and “%” representing the quantity ratio are based on mass unless otherwise specified.

(Antimicrobial composition)
The antibacterial composition of the present invention is a composition containing at least a fatty acid having 6 to 12 carbon atoms and a monoglycerin fatty acid ester; and kills Pseudomonas aeruginosa at a concentration of 2000 ppm or less in the antibacterial test. It is characterized by having antibacterial activity.

(Metastable micelle)
In the present invention, for example, the HLB value of each component of fatty acid and monoglycerin fatty acid ester (in the case of including other suitable components also includes those “other components”) is important ( Details will be described later).

(Action mechanism of the composition of the present invention)
According to the knowledge of the present inventors, the mechanism of action of the composition of the present invention is presumed as follows.

  That is, when the composition of the present invention acts on microorganisms, “metastable micelles” are formed by the composition. Then, it is presumed that the surface membrane of the micelle partially breaks on the surface of the living body (for example, virus) membrane (that is, the lipid bilayer), and the contents of the composition enter the living body membrane to exert the effect. Is done.

(Method for confirming metastable micelles)
In the present invention, whether or not “metastable micelles” are formed can be confirmed by the following test.

  That is, 100 ml of distilled water is put into a beaker having a capacity of about 200 ml (pH is set in the range of 6.5 to 7.5). The composition of the present invention (1 gram) is precisely weighed, put into the above beaker and dissolved to form an emulsion. Then, leave at room temperature. And after setting it as an emulsion state in this way, time until it isolate | separates into an oil layer and a water layer is measured. In such a test, when the time (Ts) from emulsion formation to separation into an oil layer and an aqueous layer is 2 days (48 hours) to 6 days (144 hours), the micelles according to the composition of the present invention Judge as “metastable micelle”. When the micelle according to the composition of the present invention is a “metastable micelle”, this Ts is preferably 2.5 days (60 hours) to 5 days (120 hours), and particularly 3 days (72 hours) to 4 days. (96 hours) is preferable.

  On the other hand, generally, unstable micelles are separated into an oil layer and an aqueous layer, for example, in “one day”. Furthermore, stable micelles (eg, laundry detergent micelles) remain stable emulsions even after “7 days”.

(Emulsion stability)
In order to maintain a stable emulsion state over a long period of time, a considerable amount of different types of surfactants are introduced into the oil phase using HLB as a guide, and the surfactant adsorbing film around the oil droplet particles is thickened. Often to do. That is, a stable emulsion inherently has one aspect of suppressing the functionality of oil droplets.

  From Table 3, it can be seen that the fatty acid itself, which is oily, has the greatest ability to sterilize Pseudomonas aeruginosa, but the fatty acid and water instantaneously mechanically form an emulsion, but immediately phase separated. Usually not practical. On the other hand, in order to maximize the sterilizing power of fatty acids, a semi-stable emulsion that apparently maintains a stable emulsion state for about several hours with the fatty acid particles coming out as much as possible. The composition of the present invention was devised as a practical composition to be formed.

  In the “metastable emulsion” system, when diluted several hundred times with water, it immediately becomes an emulsion state. For example, after about 3 hours, oil droplets gradually float on the surface, and in about 10 hours, It may be separated into two or three phases. The oil droplets of the system can be composed of, for example, a fatty acid having an HLB of about 6 and a glycerin monocaprylate having an HLB of about 7, and a sorbitan monocaprylate having an HLB of about 11. The particles before and after HLB7 have an affinity for water and oil, and are convenient for sterilization. However, fatty acids and these surfactants alone do not form a stable emulsion but immediately phase separate. .

  In the present invention, in such a system, sucrose monolaurate, polyglycerin laurate, twin 80, and anionic surfactants, which are non-ionic surfactants having a high HLB of about 15, are used. Some sodium dialkylsulfosuccinate is introduced to such an extent that a metastable emulsion is formed. For this reason, according to this invention, the water-soluble antibacterial composition which can kill Pseudomonas aeruginosa efficiently can be obtained.

(Example of formation conditions of metastable emulsion i) The total amount of fatty acid, glycerin monocaprylate and sorbitan monocaprylate is 50 wt. % Or more, high HLB surfactant 30 wt. % Or less is preferable.
For example, in Examples 12 and 13, which will be described later, a high HLB surfactant is 40 wt. Therefore, the hydrophobic particles of fatty acid + glycerin monocaprylate are protected by the high HLB surfactant adsorption layer, and the bactericidal action tends to be slightly reduced. In Example 5-8, the high HLB surfactant combined with sucrose monolacrate and polyglycerin lactate was 40 wt. However, these high HLB surfactants are also easily adsorbed to glycoproteins, and have a characteristic that their bactericidal activity does not decrease because they themselves exhibit bactericidal action.

  ii) When tannic acid or propyl gallate is introduced into a system such as fatty acid, glycerin monocaprylate, sorbitan monocaprylate, a metastable emulsion is easily formed. In addition, both are useful in killing Pseudomonas aeruginosa since the coagulation power of the protein is strong even in a small amount (Examples 2, 3, and 4).

(Antimicrobial test using Pseudomonas aeruginosa)
Conventionally, the inactivation ability test against avian influenza virus, which has become a serious threat in recent years, is not only a test that can be performed only by a specific specified organization, and the cost of the test evaluation is It must be quite expensive.

  On the other hand, so-called antibacterial tests are generally evaluated against general bacteria such as Escherichia coli, Pseudomonas aeruginosa, Salmonella, and Staphylococcus aureus, and fungi such as yeast and Aspergillus niger. According to the inventor's knowledge, many conventionally known antibacterial agents show strong activity against gram-positive bacteria such as Staphylococcus aureus, but against gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa. Only show relatively weak activity. In particular, many of the known antibacterial agents exhibit very weak activity against Pseudomonas aeruginosa.

(Pseudomonas aeruginosa)
Pseudomonas aeruginosa is a resident microorganism that inhabits everywhere in the natural environment. Unlike other microorganisms, Pseudomonas aeruginosa secretes a comboid, which is a kind of glycoprotein, forms a so-called biofilm, and grows and survives therein. It is considered that the penetration of antibacterial agents due to the presence of this biofilm is one of the factors that make it more difficult to sterilize than other general bacteria.

  The avian influenza virus and Pseudomonas aeruginosa have completely different structures and properties. However, as a result of intensive research, the present inventor has shown that antibacterial activity against Pseudomonas aeruginosa under specific conditions is a virus such as avian influenza virus. It has been found that this is an excellent index for the inactivation effect on sucrose. According to the knowledge of the present inventor, both virus inactivating power and antibacterial power are due to the denaturation action of the protein involved and the coagulation action of the protein, and thus kill Pseudomonas aeruginosa in a low concentration in a short time. The substance is presumed to be effective against viruses such as avian influenza virus.

(Each component)
Hereafter, each component which comprises the antibacterial composition of this invention is described.
(C6-C12 fatty acid)
As long as it is a fatty acid having 6 to 12 carbon atoms, it is not particularly limited. From the viewpoint of convenience of use such as being hard to solidify at room temperature, for example, caprylic acid C ₅ H ₁₁ COOH, caproic acid C ₉ H ₁₉ COOH, capric acid C ₁₁ H ₂₃ COOH can be suitably used. Among them, caprylic acid can be particularly preferably used.

(Monoglycerin fatty acid ester)
There is no particular limitation as long as it is a monoglycerin fatty acid ester. From the viewpoint of amphiphilicity and availability, for example, glyceryl hexanoate, glyceryl octanoate, glyceryl caprate, glyceryl laurate, glyceryl caproate, and glyceryl succinate can be suitably used. Of these, glyceryl octoate is particularly suitable.

(Suitable ratio and concentration of each component)
In an embodiment in which the composition of the present invention is a composition containing a fatty acid having 6 to 12 carbon atoms and a monoglycerin fatty acid ester, the amount ratio of the combination of these components is the specific Pseudomonas aeruginosa described above. There is no particular limitation as long as it has an antibacterial ability to kill. From the point of the combination effect of these components, for example, when the content of the fatty acid having 6 to 12 carbon atoms in the composition is “100 parts” (standard), the content of the monoglycerin fatty acid ester is The amount is preferably 20 to 200 parts, more preferably 50 to 150 parts (particularly preferably 80 to 120 parts).

(Preferable combination of each component)
In an embodiment in which the composition of the present invention is a composition containing a fatty acid having 6 to 12 carbon atoms and a monoglycerin fatty acid ester, the combination or the ratio of these components is the specific Pseudomonas aeruginosa described above. As long as it has an antibacterial activity that kills, there is no particular limitation. From the viewpoint of the combination effect of these components, for example, the following combinations can be suitably used.

<C6-C12 fatty acid><Monoglycerol fatty acid ester>
Caprylic acid monoglyceryl caprate caproic acid monoglyceryl caprate capric acid monoglyceryl caprate lauric acid monoglyceryl caprate

The caprylic acid, caproic acid and capric acid described above are “equivalent” with respect to the effects in the present invention. These and lauric acid are also “substantially equivalent” with respect to the effects in the present invention. Therefore, these fatty acids can be used by appropriately mixing in consideration of other factors (for example, solubility in a solvent, etc.).
(Other preferred components)
The antibacterial composition of this invention can also contain another component as needed. Examples of such “other components” include polyhydric phenol derivatives, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, and the like.

(Polyhydric phenol derivative)
As the polyhydric phenol derivative, for example, tannic acid, gallic acid, and the like can be suitably used from the viewpoint that the antibacterial activity can be exhibited at a low concentration. Among these, tannic acid can be particularly preferably used.

(Polyglycerin fatty acid ester)
As polyglyceryl fatty acid ester, from the viewpoint of easy handling, easy solubility, and HLB, for example, diglyceryl monooctanoate, diglyceryl monodecanoate, diglyceryl monolaurate, decaglyceryl monolaurate, decaglyceryl monooctanoate, etc. Can be suitably used. Among these, decaglyceryl monolaurate can be used particularly preferably.

(Sucrose fatty acid ester)
As the sucrose fatty acid ester, from the viewpoint of easy solubility and HLB, for example, sucrose laurate, sucrose stearate, sucrose palmitate and the like can be suitably used. Of these, sucrose laurate can be used particularly preferably.

(Sorbitan fatty acid ester)
As the sorbitan fatty acid ester, for example, sorbitan monocaprylate can be suitably used from the viewpoint of bactericidal power.

(Preferable combination of each component)
In the embodiment of the composition of the present invention that contains other additives in addition to the fatty acid having 6 to 12 carbon atoms and monoglycerin fatty acid ester, any combination or quantitative ratio of these components is the specific green There is no particular limitation as long as it has antibacterial activity to kill Pseudomonas aeruginosa. From the viewpoint of a good balance between ease of handling and antibacterial properties, for example, combinations shown in the following “table” can be suitably used.

（数字の単位は、ｗｔ％である。）
（各成分の好適な量比・濃度）
炭素数が６〜１２の脂肪酸およびモノグリセリン脂肪酸エステルに加えて、他の添加剤をも含む本発明の組成物の態様において、これらの成分の組合せの量比は、上記した特定の緑膿菌を死滅させる抗菌力を有する限り特に制限されない。取扱容易性と抗菌性との良好なバランスの点からは、例えば、上記「表１」に示した量比が、好適に使用可能である。

(The unit of the numbers is wt%.)
(Suitable ratio and concentration of each component)
In the embodiment of the composition of the present invention which contains other additives in addition to the fatty acid having 6 to 12 carbon atoms and monoglycerin fatty acid ester, the ratio of the combination of these components is the specific Pseudomonas aeruginosa described above. As long as it has an antibacterial activity that kills, there is no particular limitation. From the viewpoint of a good balance between ease of handling and antibacterial properties, for example, the quantitative ratios shown in the above “Table 1” can be suitably used.

Fatty acids having 6 to 12 carbon atoms: 100 parts (standard)
Monoglycerin fatty acid ester: preferably 20 to 200 parts, more preferably 50 to 150 parts (particularly preferably 80 to 120 parts)
Polyhydric phenol derivative: 20 to 200 parts, more preferably 50 to 150 parts (particularly preferably 80 to 120 parts)
Polyglycerin fatty acid ester: preferably 10 to 150 parts, more preferably 20 to 120 parts (particularly preferably 25 to 100 parts)
Sucrose fatty acid ester: preferably 10 to 150 parts, more preferably 20 to 120 parts (particularly preferably 25 to 100 parts)
Sorbitan fatty acid ester: preferably 10 to 150 parts, more preferably 20 to 120 parts (particularly preferably 25 to 100 parts)

(Criteria for selecting each component)
Each component constituting the composition of the present invention is not limited in terms of the use of the present invention (for example, a virus inactivating agent), and is preferably safe and harmless and hardly burdens the environment. Therefore, it is preferable to select from substances and materials used in foods (for example, tannic acid, propyl gallate, various carboxylic acids, glycerin fatty acid esters, etc.).

(Antimicrobial test using Pseudomonas aeruginosa)
In the present invention, the antibacterial test for Pseudomonas aeruginosa can be performed by a general method. One example is shown in “Reference Example 1” described later.

(Use of the composition of the present invention)
Since the composition of the present invention is water-soluble, it is considered effective against norovirus having high hydrophilicity.

(Use concentration of the composition of the present invention)
As shown in the Examples described later, the composition of the present invention can exhibit sufficient antibacterial activity at a concentration of 2000 ppm or less. Although it depends on the conditions, the composition of the present invention has a possibility of exhibiting sufficient antibacterial activity even at a concentration of 1000 ppm or less.

  Hereinafter, the present invention will be described more specifically with reference to examples.

Reference example 1
(An example of antibacterial test using Pseudomonas aeruginosa)
The Pseudomonas aeruginosa group was cultured for 3 days at 36 ° C. for 12 hours in a culture solution of Heart Infusion Bouillon (manufactured by Nissui Pharmaceutical Co., Ltd.), and the bacterial count was adjusted to 108 / ml. 1 ml of this culture solution is dropped into various material solutions and sensitized for 5 minutes. Then, 1 ml of the sample is stirred and mixed with 20 to 25 ml of a standard agar medium (manufactured by Nissui Pharmaceutical Co., Ltd.) and coagulated at 37 ° C. for 24 hours. Culturing and observing the survival of the bacteria (For details of the method and conditions of such antibacterial test, see, for example, “The Sanitary Test Method / Summary” edited by the Japanese Pharmaceutical Society, pages 39-43, March 31, 2000. Japan, Kanbara Publishing Co., Ltd. can be referred to).

  The concentration of various substances that can kill Pseudomonas aeruginosa in 5 minutes by this method was as follows.

（ｐｐｍ）

(Ppm)

Example 1
The inactivation ability of avian influenza virus was evaluated by the following prescription. This evaluation was outsourced to the Chinese National Center for Outpatients and Diseases.

（ｗｔ．％）

(Wt.%)

Example 2
In the same manner as in Example 1, the inactivation ability of the avian influenza virus was evaluated according to the following prescription. This evaluation was outsourced to the Chinese National Center for Outpatients and Diseases.

<Details of antibacterial test>

Example 3
(Kyoto Sangyo University)
In the same manner as in Example 1, the inactivation ability of the avian influenza virus was evaluated according to the following prescription. This evaluation was commissioned to Kyoto Sangyo University (Avian Influenza Research Center).

Example 4
(Kyoto Sangyo University)
In the same manner as in Example 1, the inactivation ability of the avian influenza virus was evaluated according to the following prescription. This evaluation was commissioned to Kyoto Sangyo University.

(Results of Examples 1 to 4)
In Examples 1 and 2, it was found that the composition of the present invention can be eliminated by contacting a highly pathogenic H5N1 avian influenza virus with a 1,000-fold aqueous solution for 1 hour. In addition, Example 2 is a prescription especially assuming a virus inactivating agent by oral administration.

  In Examples 3 and 4, it was found that the virus can be inactivated by contacting the H5N3 strain with a 200, 1,000-fold aqueous solution for 10 minutes, respectively, using the composition of the present invention.

  In any of Examples 1, 2, 3, and 4, it was found that Pseudomonas aeruginosa can be killed in 10 minutes with a 500-fold diluted aqueous solution of the composition of the present invention.

  In Example 3, as a result of sterilization tests on Staphylococcus aureus and Salmonella, it was found that both can be killed in 1,000 minutes with 1,000-fold diluted water.

  Detailed methods and conditions of these Pseudomonas aeruginosa are shown in Tables 7a to 7c below.

  From the above, it was found that a substance capable of killing Pseudomonas aeruginosa in a short time is also effective against avian influenza virus.

(Details of methods used in Examples 3 and 4)
Details of the above method are shown in the table below.

上記により、以下の表に示す結果が得られた。

As a result, the results shown in the following table were obtained.

(Details of results of Examples 1 and 2)
As a result, the results shown in the following table were obtained.

Claims (8)

A composition comprising at least a fatty acid having 6 to 12 carbon atoms and a monoglycerin fatty acid ester; and
An antibacterial composition having an antibacterial activity that kills Pseudomonas aeruginosa at a concentration of 2000 ppm or less in an antibacterial test. The fatty acid having 6 to 12 carbon atoms is one or more fatty acids selected from the group consisting of caprylic acid C ₅ H ₁₁ COOH, caproic acid C ₉ H ₁₉ COOH, and capric acid C ₁₁ H ₂₃ COOH. 1. The antibacterial composition according to 1.   The monoglycerin fatty acid ester is one or more fatty acids selected from the group consisting of glyceryl hexanoate, glyceryl octanoate, glyceryl caprate, glyceryl laurate, glyceryl caproate, and glyceryl succinate. The antibacterial composition as described.   The antibacterial composition according to any one of claims 1 to 3, further comprising one or more additives selected from the group consisting of polyphenol derivatives, polyglycerin fatty acid esters, sucrose fatty acid esters, and sorbitan fatty acid esters. .   The antimicrobial composition according to any one of claims 1 to 4, wherein the polyhydric phenol derivative is one or more selected from the group consisting of tannic acid and gallic acid.   The polyglycerin fatty acid ester derivative is one or more fatty acids selected from the group consisting of diglyceryl monooctanoate, diglyceryl monodecanoate, diglyceryl monolaurate, decaglyceryl monolaurate, and decaglyceryl monooctanoate. The antibacterial composition in any one of 1-5.   The antibacterial composition according to any one of claims 1 to 6, wherein the sucrose fatty acid ester is one or more selected from the group consisting of sucrose laurate, sucrose stearate, and sucrose palmitate. object.   The antimicrobial composition according to any one of claims 1 to 7, wherein the sorbitan fatty acid ester is sorbitan monocaprylate.