JP2868206B2 - Composition for controlling harmful microorganisms for disinfection and / or preservation - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to preservatives for preservatives and chemical disinfectants for cleaning and preserving solutions for contact lenses, various pharmaceutical preparations, quasi-drugs and cosmetics such as eye drops and dental agents. Disinfectants and disinfectants, and food,
The present invention relates to a composition for controlling harmful microorganisms, which is useful as a preservative for cosmetics, household and industrial detergents, and the like.

[0002]

2. Description of the Related Art In industry, development of antibacterial agents, disinfectants (bactericides) and preservatives which are highly safe and effective for living organisms is obviously important. These fields are enormous and diversified, and cannot be explained in a single word. However, antibacterial agents include pathogenic microorganisms (bacteria, fungi, viruses, etc.) that have propagated in vivo, surgical layers, wound sites, and the like. ) Is a preparation that acts bactericidally or bacteriostatically, and is also applied as a prophylactic agent for infection.

On the other hand, disinfectants are used for wound sites, medical tools such as surgical instruments, contact lenses, ophthalmology including conjunctival sac, dental for the oral cavity and throat, fingers and skin, obstetrics and gynecology and urology. It is widely used as a drug for killing pathogens or preventing infection. Preservatives (preservatives) are mixed in cleaning and preservatives for contact lenses, various pharmaceutical solutions including eye drops, quasi-drugs, food and drinking water, cosmetics, and household and industrial detergents. It is used as an additive for preventing germs, molds and the like from propagating bactericidal or bacteriostatic. As described above, antibacterial agents, disinfectants, and preservatives are diversified, but technical development has been made according to the purpose, effect, application, etc. of each field.

For cleaning and preserving solutions for contact lenses
Preservatives used include sorbic acid and boric acid-borax
There is. These have relatively low bactericidal activity (bacteriostatic
Use), often the propagation of microorganisms, and contamination in the container
To be observed. In addition, benzalco chloride has a strong bactericidal effect
Ium, chlorobutanol, chlorhexidigluconate
And parahydroxybenzoic acid esters
Soft contact lenses and tact lenses
And storage on oxygen and oxygen permeable hard contact lenses
Product phenomenon occurs, resulting in lens deformation, deterioration and
Corners generated by the sustained release of accumulated preservatives from the lens
Difficult to use the above preservatives due to conjunctival disorders
(Japanese Patent Publication No. 8-16042 and Nikkore magazine34
(4), pp. 267-276, 1992).

[0005] Chemical disinfectants included in multipurpose care formulations for contact lenses include polyhexamethylene biguanide,
Chlorhexidine and polyquaternium are used. However, when higher concentrations of these disinfectants are used due to emphasis on bactericidal properties, cell damage and corneal coloring may occur. On the other hand, if a disinfectant is used at a lower concentration in order to suppress these obstacles, the antibacterial activity is reduced, so that there is still a considerable problem in the complexity of prescribing the disinfectant (Japanese Patent Publication No. 6-49642). Reference). In addition, some disinfectants of 3% hydrogen peroxide have a low bactericidal effect depending on the type of microorganism, and may cause corneal damage if misused.

[0006] Various pharmaceutical liquids including eye drops using reusable containers include benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, paraoxybenzoates, sorbic acid, chlorobutanol and thimerosal. Has been used as an agent. However, cationic surfactants such as benzalkonium chloride, benzethonium chloride and chlorhexidine gluconate, p-hydroxybenzoates and chlorobutanol have strong antibacterial activity, but eye drops containing these substances are frequently applied. It is said that preservatives greatly affect preservatives and cause corneal disorders for people with abnormal tear kinetics such as corneal scars or dry eye symptoms (Ophthalmology 3)
1 , pages 43-48, 1989 and Ophthalmology 33 , 533.
538 pages, 1991). Sorbic acid has a small preservative effect as described above, and thimerosal is a mercury compound, so its use is not currently recognized in Japan.

Disinfectants used as eye drops include benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, and alkylpolyaminoethylglycine. These are used for washing and disinfecting the conjunctival sac, and have side effects such as eye irritation, shock, rash, and itching. For dental use, azulene is used as a mouthwash for disinfecting the oral cavity and throat and preventing infection of tooth extraction wounds.
Disinfectants such as povidone-iodine, the cationic surfactants domiphen bromide and benzethonium chloride have been used.

[0008]

SUMMARY OF THE INVENTION An object of the present invention is to disinfect
And / or to provide a new composition for controlling harmful microorganisms for preservation . Another object of the present invention is to provide a composition that is excellent in biosafety and excellent in disinfecting and preserving effects. Still another object of the present invention is to provide
Preservatives for cleaning and preserving liquids for contact lenses and their chemical disinfectants, as well as preservatives and disinfectants for various pharmaceutical preparations including eye drops and dental agents, quasi-drugs and foods, cosmetics, household An object of the present invention is to provide a composition for controlling harmful microorganisms for disinfection and / or preservation, which can be used as a preservative for industrial detergents.

[0009]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, a surfactant which does not exhibit its disinfecting / preserving effect alone or has a weak effect, aqueous solution are allowed to coexist at least three components of a particular non-reducing saccharides Contact and chelating agents, surprisingly, was able to express a strong disinfecting and antiseptic effect, it can be applied to various industrial fields with it A formulation was prepared to complete the invention.

That is, according to the present invention, the above objects and advantages of the present invention include (A) a surfactant, and (B) 1-O-
Alkyl glucose, sucrose, trehalose,
Maltitol, xylitol, arabitol, ribitol
Le, Threitol, Dulsit, Raffinose, Genchi
Anose, melezitose, planteose, stachyau
At least selected from the group consisting of
Both comprising one non-reducing saccharides Contact and (C) a chelating agent, harmful microorganisms controlling compositions for disinfecting and / or preservative is provided. Each component of the present invention is widely used in various fields, and is also guaranteed in biosafety.
The use of preservatives is completely unknown to date,
Therefore, if the biosafety of each preparation according to the purpose of use is confirmed, it can be a revolutionary disinfection and preservative system that can be used in various fields.

The surfactant (A) used in the composition of the present invention may be selected from cationic, anionic, zwitterionic and nonionic compounds according to the purpose of use and the target industrial field. At least one selected one can be used.

As the cationic surfactant, at least one selected from alkylamine salts, alkylammonium salts and the like can be used. Examples of the alkylamine salt include N-coconut fatty acid acyl-L-arginine ethyl.DL
-Pyrrolidone carboxylate.

[0013] As the anionic surfactant, for example alkylbenzene Ho phosphate, alkyl sulfate, alpha-olefin sulfonate Ho phosphate, polyoxyethylene alkyl ether sulfate, alkyloyl methyl taurine, alkyloyl benzalkonium Singh, N- acyl Sarcosine, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl phenyl ether sulfate, hydrogenated coconut oil fatty acid glyceryl sulfate, carboxylated polyoxyethylene lauryl ether or their sodium, potassium and triethanolamine salts and methyltaurine derivatives and their derivatives At least one selected from the group of salts can be used.

As the zwitterionic surfactant, for example, N
-Lauroylaminopropyl-N, N-dimethylglycine, N-cocoylaminopropyl-N, N-dimethylglycine, N-lauroylaminopropyl-N-carboxymethyl-N-hydroxyethylglycine, N-oleylaminopropyl-N- Carboxymethyl-N-hydroxyethylglycine, N-3-dodecyloxy-2-hydroxypropyl-N, N-dimethylglycine, N-cocoylaminopropyl-N-hydroxyethyl-3-aminopropionic acid, tri [3- (N -Cocoylaminoethyl-N-hydroxyethyl-N-carboxymethyl) amino-2-hydroxypropanol] phosphate, alkyldiaminoethylglycine hydrochloride (the alkyl group is mainly composed of those containing 12 and 14 carbon atoms) Etc.) It can be used at least one member selected from these groups.

Examples of the nonionic surfactant include poly (oxyethylene) -poly (oxypropylene) block copolymer (poloxamer), polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether, polyoxyethylene alkyl ester, and polyoxyethylene alkyl ester. Oxyethylene sorbitan alkyl ester, polyoxyethylene hydrogenated castor oil, fatty acid monoglyceride, propylene glycol fatty acid ester, fatty acid sucrose ester and poly (oxyethylene) -poly (oxypropylene)
Ethylenediamine condensate (poloxamine) and the like can be used alone or in combination of two or more.
The above surfactant is used in an amount of 0.00000 of the total amount of the preparation of the present invention.
It is used in a concentration range of 5 to 1.0% by weight.

(B) Non-reducing saccharides include 1-O
-Alkyl glucose, sucrose, trehalose
Vinegar, Ma Ruchitoru, xylitol Le, A Rabitoru, ribitol, threitol, Darushi' door, La Finosu, gentianose, melezitose, Plante Orth, Sutaki <br/> O scan and Bell bus course can be used. These Ru can be used in combination either alone or in combination. Non-reducing saccharides of these is 0.01 to 10.0 wt% of the whole preparation
It is used in the range of the concentration.

As the chelating agent (C), ethylenediaminetetraacetic acid, gluconic acid, citric acid, tartaric acid, diethylenetriaminepentaacetic acid and their sodium and potassium salts, sodium polyphosphate and sodium nitrilotriacetate are preferred. Disodium tetraacetate is particularly preferred. These chelating agents are used in a concentration range of 0.01 to 1.0% by weight of the whole preparation.

The microbial pests controlling composition of the present invention, the above (A) surfactant, (B) a particular non-reducing saccharides your good <br/> Beauty (C) chelating agent an aqueous medium It is prepared by dissolving in As the aqueous medium, an aqueous solution in which an isotonic agent and / or a buffer or a hydrophilicity-imparting agent is dissolved in purified water is preferably used. The tonicity agent, buffering agent or hydrophilicity-imparting agent is preferably prepared by dissolving each in 2% by weight or less in purified water. As tonicity agents, sodium chloride and potassium chloride are preferred. As the buffer, for example, sodium dihydrogen phosphate and monohydrogen phosphate
Phosphate buffer such as disodium, borax and such borate-based buffers and tris hydroxymethyl amino borate
Tris buffers such as methane (tromethamine) and dilute hydrochloric acid and trismalate and dilute caustic soda solution are preferred. As the hydrophilicity-imparting agent, polyvinylpyrrolidone, polyvinyl alcohol, sodium hyaluronate, hydroxypropylmethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, glycerin, propylene glycol, dextran, and polyquaterniums are preferable.

The compositions of the present invention, as a result of preservative efficacy testing of harmful microorganisms composition for controlling, surfactants, three specific <br/> non-reducing saccharides Contact and chelating agents The preparation containing the main component showed a strong preservative effect. However, the preparation lacking at least one of the three main components and the preparation containing only the main component had no or weak preservative effect. Although the antibacterial mechanism of the composition of the present invention is unknown at present, the role of the non-reducing saccharide in the present antibacterial system is very interesting, and is left as a future research subject. I have.

According to the composition of the present invention, in terms of biosafety, anionic and nonionic surfactants among the surfactants used in the preparation are used for cleaning and cleaning contact lenses.
It is already used in preservatives, and has been used in various pharmaceutical preparations, quasi-drugs and cosmetics, including eye drops and dental agents, and as a food additive, the above-mentioned nonionic surfactant Some have been licensed and their safety has been confirmed. Similarly, disodium ethylenediaminetetraacetate, which is a chelating agent, is used as a washing / preserving solution for contact lenses, a disinfecting solution thereof, and a stabilizer for various pharmaceuticals and cosmetics. It is also used as an antioxidant in canned and soft drinks as a food additive.

[0021] In a particular non-reducing saccharides, trehalose and the like <br/> expressing strongest antimicrobial activity of the present invention system in particular. Trehalose is metabolized to carbon dioxide by intravenous injection in rabbits (Biochem. Physio
l., 50B , p. 221 (1975)), there is a possibility of using an infusion solution for humans, and a nutritional composition containing fat and an amino acid containing amino acid of an infusion component containing the substance is biosafe. That there is no problem in performance (Japanese Patent Laid-Open No.
No. 9664 and JP-A-6-70718),
And use of the food (see Japanese Patent Laid-Open No. 6-170221), etc. have been reported. Trehalose I follow is a high bio-safety materials.

[0022] Thus, the surfactant used in the compositions of the present invention, 3 principal components of a particular non-reducing saccharides Contact and chelating agents, have their use results, also bio-safety It has been confirmed that the composition of the present invention can be used as a preservative and a chemical disinfectant for cleaning and preserving solutions for contact lenses as a preservative and disinfectant for pharmaceutical preparations including eye drops and dental agents, and cosmetics. It can be used as an ingredient and as a preservative in foods, cosmetics, household and industrial detergents.

[0023]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto. Example 1 Solutions No. 1 to No. 6 shown in Table 1 were prepared.

[0024]

[Table 1]

The solution is prepared by dissolving hydroxyethyl cellulose in about 80% distilled water and then dissolving anhydrous disodium phosphate and anhydrous monosodium phosphate. Thereafter, disodium ethylenediaminetetraacetate, trehalose, and glycerin are dissolved. Finally, sodium α-olefin sulfonate is dissolved, and the volume is adjusted to a predetermined volume with distilled water (pH of the aqueous solution is 7.2). E. col (E. col)
i), P. aeruginosa (P.aeruginos
a), S. aureus and C. albicans are added at about 10 ⁶ to 10 ⁸ per ml, and the mixture is allowed to stand at 25 ° C. After 3 days and 7 days, 1 ml of each of the solutions inoculated with the bacteria is mixed with an agar medium (Tables 3 and 4), cultured in a plastic dish, and the number of viable bacteria is measured. Table 2 shows the results.

[0026]

[Table 2]

The solution containing surfactant is active agents α- olefin sulfonate phon sodium, non-reducing saccharides in a trehalose, disodium ethylenediaminetetraacetate is key rate <br/> preparative agent No. 4 and 5 showed preservative effectiveness, solutions No.1,2,3 and α- olefin sulfonate phon sodium does not contain any one, trehalose or bets
Solution No. 6 containing neither Reharosu and glycerin and disodium ethylenediaminetetraacetate has preservative efficacy with respect to all the test microorganisms in preservative was not weak or hardly observed.

[0028]

[Table 3]

[0029]

[Table 4]

Example 2 No. 7 to No. 8 solutions shown in Table 5 were prepared.

[0031]

[Table 5]

A solution can be prepared by dissolving a hydrophilicity-imparting agent, a buffer, a chelating agent, a tonicity agent, a non-reducing saccharide, and a surfactant in the same order as in Example 1 (the pH of the aqueous solution is 8.0). E. To a solution of Table 5 in the same manner as in Example 1,
E. coli and C. albicans (Ca)
lbicans), and the number of viable bacteria was measured 3 days later. Table 6 shows the results.

[0033]

[Table 6]

From the results shown in Table 6 , even if the buffer is changed, it can be preserved.
It was confirmed that shows the preservative efficacy with. In addition, the addition of non-reducing saccharides enhanced the preservative effect associated with preservation.

Example 3 Solutions No. 9 to No. 11 shown in Table 7 were prepared.

[0036]

[Table 7]

The solution has a pH of (an aqueous solution can be prepared by dissolving in the order of Example 1 in the same manner as in the hydrophilic agent, a buffering agent, chelating agents, tonicity agents, non-reducing saccharides, boundary surface active agent 7.2). Solution of Table 7 in E. coli (E. coli), P. aeruginosa (P. aeruginosa), S. aureus (S.aureus) and Sea albicans a (C.albicans) per 1 ml 10 ⁶
Approximately 10 to 10 ⁸ cells were inoculated, and the number of viable cells up to 6 hours was measured. Table 8 shows the results.

[0038]

[Table 8]

The results in Table 8 show that the blended preparation of trehalose, which is a non-reducing sugar, sodium α-olefin sulfonate, which is a surfactant , and disodium ethylenediaminetetraacetate, which is a chelating agent, is as follows. , And also exhibited a sufficient disinfecting effect.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A01N 41:04 37:42) (72) Inventor Shingo Hishiya 156-5 Kamimidai, Toyooka City, Hyogo Pref. ) Inventor Saito Fumio 156-5, Kamidaidai, Toyooka City, Hyogo Pref., Ltd. (72) Inventor Takashi Fujii 156-5, Kamidaidai, Toyooka City, Hyogo Pref. 54-8721 (JP, A) JP-A-4-51015 (JP, A) JP-A-7-126109 (JP, A) JP-A-8-152585 (JP, A) JP-A-63-188610 (JP, A) A) JP-A-54-41333 (JP, A) JP-A-3-68503 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A01N 43/16 A01N 25/30 WPI ( DIALOG)

Claims (3)

(57) [Claims] 1. A surfactant, (B) 1-O-al
Kill glucose, sucrose, trehalose, mal
Tititol, xylitol, arabitol, ribitol,
Threitol, Dulcit, Raffinose, Gentian
Sauce, melezitose, planteose, stachyose
At least selected from the group consisting of
Characterized in that it contains one of the non-reducing saccharides Contact and (C) a chelating agent, antiseptic and / or for preservative
A composition for controlling harmful microorganisms. 2. The composition according to claim 1, wherein the surfactant is at least one selected from the group consisting of cationic, anionic, zwitterionic and nonionic compounds. 3. The chelating agent is ethylenediaminetetravinegar.
Acid, gluconic acid, citric acid, tartaric acid, diethylene tria
Minpentaacetic acid and the sodium salts of these acids and the same
Potassium salts of these acids, sodium polyphosphate and nitrite
2. The method according to claim 1, wherein said substance is selected from the group consisting of sodium lirotriacetate.
A composition as described.