JP2011208138A - Detergent for medical device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a detergent for medical devices, having no corrosivity, little in environmental load, having excellent detergency, and keeping the detergency for a long term.SOLUTION: The detergent for medical devices comprises at least one compound selected from the group consisting of a compound represented by general formula (1) and a salt thereof, an enzyme and water. Preferably, a compound such as N-acetylarginine ethyl ester hydrochloride or arginine hydrochloride is further contained. (Wherein, X represents imino, O or S).

Description

  The present invention relates to a cleaning agent for medical devices.

  Artificial dialysis for blood washing is a treatment method in which the blood of a patient is indirectly contacted with a dialysate through a semipermeable membrane to remove waste products in the blood, adjust the salt concentration, and remove water.

Various stains adhere to the artificial dialysis machine and the pipes accompanying it. For example, in addition to bacteria entering from an open part such as a tank, protein stains derived from blood or the like, fat, etc., calcium carbonate or the like adheres.
As a method for cleaning and disinfecting an artificial dialysis machine and its peripheral devices,
(1) A method in which sodium hypochlorite is used for the purpose of washing and disinfecting waste products such as proteins filtered from the patient's body, and a method using acetic acid for the purpose of washing calcium carbonate,
(2) A method in which a peracetic acid aqueous solution is used for the purpose of disinfection and washing of calcium carbonate, and a method of using sodium hypochlorite for the purpose of washing waste products such as proteins filtered from the patient's body (for example, , See Patent Document 1),
(3) Disinfecting, washing calcium carbonate, and washing waste products such as protein filtered from the patient's body at once using an aqueous solution that has been improved by adding inorganic acid such as phosphoric acid to peracetic acid aqueous solution There is a method (for example, see Patent Document 2).
However, the method (1) and the method (2) not only cause deterioration of equipment parts and piping due to the strong corrosiveness that is a characteristic of sodium hypochlorite, but also two types of cleaning methods. Therefore, there is a problem that work is complicated and a great deal of labor and time are consumed. Further, in an actual dialysis treatment site, treatment may be performed until late at night, and two types of cleaning methods may not be performed continuously. Furthermore, there is also a problem that chlorine is discharged as a waste liquid without being treated, thereby adversely affecting the environment.
Moreover, the method of (3) is disclosing the disinfecting | cleaning detergent composition which contains 20% or 40% of phosphoric acid in the Example of patent document 2, for example. However, if a large amount of phosphoric acid is used in this way, phosphorus is a typical substance that is an environmentally hazardous substance. Therefore, if washing is performed by this method, it is inevitable that the natural environment will be greatly affected.

Further, it contains hydrogen peroxide 3.5-6%, organic acid 5-30%, and organic peracid 0.4-3.4%, and the weight ratio of (organic acid + organic peracid) / hydrogen peroxide is A disinfectant cleaning agent for medical devices composed of one or more aqueous solutions has been proposed (see, for example, Patent Document 3).
However, although disinfecting detergents for medical devices containing hydrogen peroxide, organic acids and organic peracids do not contain environmentally hazardous substances such as phosphoric acid, they do not have sufficient cleaning properties for proteins and other waste products and calcium carbonate. Have a problem.

  For these reasons, a method for decomposing and washing proteins using an enzyme has been proposed (Patent Document 4). The method using an enzyme is a mild cleaning method that does not require strong alkaline conditions, and the burden on the operator is reduced. However, the enzyme is very unstable in an aqueous solution and has the disadvantage that the enzyme activity decreases after storage for a certain period. Therefore, there is a big problem that the detergency deteriorates after storage for a certain period.

JP-A-8-224299 JP 2003-292996 A Japanese Patent Laid-Open No. 11-76380 JP 2006-193684 A

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a cleaning agent for medical devices that does not have corrosive properties, has a small environmental load, has excellent cleaning properties, and has long-term cleaning properties. In particular, a wide range of medical equipment such as artificial dialysis machines, endoscopes, and dental treatment equipment, and parts such as tubes and sealed containers that are associated with them, and are not cartridges or disposals, so that parts that need to be cleaned An object of the present invention is to provide a cleaning agent for medical devices which exhibits excellent performance in the above.
In the present invention, “the cleaning property is maintained for a long time” means that the difference between the cleaning property measured after storing for a certain period of time and the cleaning property measured immediately before storage is small and shows a certain cleaning property. Means.
Further, in the present invention, “highly sustained enzyme activity” means that the enzyme activity measured after storage for a certain period of time and the enzyme activity measured immediately before storage are small and show a certain enzyme activity. Means.

［式（１）中、Ｘはイミノ基、酸素原子又は硫黄原子を表す。］ The inventors of the present invention have reached the present invention as a result of studies to achieve the above object.
That is, the present invention is a medical device cleaning agent comprising at least one compound (A) selected from the group consisting of a compound represented by the following general formula (1) and a salt thereof, an enzyme (a) and water. It is a summary.

[In Formula (1), X represents an imino group, an oxygen atom, or a sulfur atom. ]

  The medical device cleaning agent of the present invention can maintain a high cleaning performance against protein stains such as blood for a long period of time, and can be particularly suitably used for a medical device cleaning agent that requires a high cleaning level.

  The medical device cleaning agent of the present invention contains at least one compound (A) selected from the group consisting of a compound represented by the following general formula (1) and a salt thereof, an enzyme (a), and water. Cleaning agent.

[In Formula (1), X represents an imino group, an oxygen atom, or a sulfur atom. ]

  When the enzyme is stored in a liquid, there is a problem that the enzyme activity is remarkably lowered due to aggregation, hydrolysis, etc. In the present invention, the above compound (A) having a specific chemical structure is used as a cleaning agent for medical devices. It can be solved by adding to.

  Specific examples of the compound represented by the general formula (1) include guanidine, urea and thiourea.

Examples of the salt of the compound represented by the general formula (1) include a guanidine salt.
Examples of the salt include hydrochloride, carbonate, borate, sulfate and phosphate.

  The compound (A) is preferably a guanidine salt and urea, more preferably a guanidine salt, and still more preferably a guanidine hydrochloride, from the viewpoint of sustaining enzyme activity.

The content (% by weight) of the compound (A) contained in the cleaning agent for medical devices of the present invention is from 0 to 0% with respect to the weight of the cleaning agent for medical devices from the viewpoint of durability of cleaning and durability of enzyme activity. 01-30 are preferable, More preferably, it is 0.02-10, Next, More preferably, it is 0.03-5, Most preferably, it is 0.05-3.
The content of the compound (A) contained in the cleaning agent for medical devices of the present invention is 1 to 1000% by weight with respect to the weight of the enzyme (a), from the viewpoint of durability of detergency and durability of enzyme activity. Is preferable, more preferably 5 to 500% by weight, and still more preferably 10 to 300% by weight.

  The medical device cleaning agent of the present invention may further contain a compound (B) represented by the following general formula (2). It is preferable to contain (B) from a viewpoint of the durability of detergency and the durability of enzyme activity.

  In general formula (2), Q represents an amino group or an alkyl group, and a part of hydrogen atoms in the alkyl group may be substituted with a substituent other than a hydrogen atom.

Examples of the alkyl group of Q include an alkyl group having 1 to 22 carbon atoms, specifically a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, an octyl group, a nonyl group, a decyl group, and a dodecyl group. , A cetyl group, a stearyl group, a behenyl group, and the like. A part of hydrogen atoms in these alkyl groups may be substituted with a substituent other than a hydrogen atom.
Examples of substituents other than hydrogen atoms include amino groups, carboxyl groups, amide groups, ester groups, imino groups, and hydroxyl groups. The number of substituents is preferably 1 to 3, more preferably 2 to 3. For example, when Q is a butyl group, (B) represents arginine when two hydrogen atoms at the terminal of the butyl group are substituted with one amino group and one carboxyl group.

  Examples of the compound (B) include arginine or a salt thereof (B-1), an arginine derivative or a salt thereof (B-2), and a guanidine derivative or a salt thereof (B-3).

  Arginine, its salt (B-1), arginine, arginine inorganic acid salt (hydrochloride, borate, phosphate, pyrophosphate, sulfate, silicate, etc.) and arginine organic acid salt (formic acid) Salt, acetate, oxalate, lactate, citrate, trimellitic acid salt and pyromellitic acid salt).

In the arginine derivative or a salt thereof (B-2), the arginine derivative is a derivative in which the α-amino group or α-carboxyl group of arginine represented by the following general formula (3) or both of these groups are substituted.
The α-amino group is substituted with an N-alkylcarbonyl-amide group (Y-1) represented by the following general formula (4) or an imino group (Y-2) represented by the general formula (5). The substitution of the α-carboxyl group is substitution to an ester group represented by the following general formula (6) or an N-alkylamide group (Z-2) represented by the following general formula (7).

  In other words, in the arginine derivative or a salt thereof (B-2), at least one of an α-amino group and an α-carboxyl group is substituted. That is, when Y is an amino group, Z is an ester group (Z-1) represented by the following general formula (6) or an N-alkylamide group (Z-2) represented by the following general formula (7). Yes, when Z is a carboxyl group, Y is an N-alkylcarbonyl-amide group (Y-1) represented by the following general formula (4) or an imino group (Y-) represented by the following general formula (5). 2).

  In general formula (3), Y represents an amino group, an N-alkylcarbonyl-amide group (Y-1) represented by the following general formula (4), or an imino group (Y-) represented by the following general formula (5). 2). Z represents a carboxyl group, an ester group (Z-1) represented by the following general formula (6), or an N-alkylamide group (Z-2) represented by the following general formula (7).

In the general formula (4), R ¹ represents a hydrogen atom or a monovalent hydrocarbon group having 1 to 36 carbon atoms, and this hydrocarbon group has a part of the hydrogen atom as a functional group other than a hydrogen atom. May be substituted.

The hydrocarbon group of R ^{1 in} the N-alkylcarbonyl-amide group (Y-1) represented by the general formula (4) is a monovalent hydrocarbon group having 1 to 36 carbon atoms, and is linear or branched Aliphatic hydrocarbon groups, alicyclic hydrocarbon groups and aromatic hydrocarbon groups.
Linear aliphatic hydrocarbon groups include methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl, nonyl, decyl, lauryl, palmityl, stearyl, oleyl and Examples include a behenyl group.
Examples of the branched aliphatic hydrocarbon group include an isopropyl group and a t-butyl group.
Examples of the alicyclic hydrocarbon group include a cyclohexyl group, a methylcyclohexyl group, and a cyclohexylmethyl group.
Examples of the aromatic hydrocarbon group include a phenyl group, a methylphenyl group, a benzyl group, a phenylethyl group, and a methylbenzyl group.
Of these hydrocarbon groups, a linear aliphatic hydrocarbon group is preferable from the viewpoint of durability of detergency and enzyme activity, more preferably a methyl group and an ethyl group, and most preferably a methyl group. .
Examples of substituents other than hydrogen atoms include amino groups, carboxyl groups, amide groups, ester groups, imino groups, and hydroxyl groups.

  Specific examples of the N-alkylcarbonyl-amide group (Y-1) represented by the general formula (4) include formamide group, acetylamide group, propionic acid amide group, butyric acid amide group, hexylic acid amide group, and cyclohexyl. Examples include an acid amide group, an octylic acid amide group, and a benzoylamide group.

In the general formula (5), R ² and R ³ each independently represent a hydrogen atom or a hydrocarbon group having 1 to 36 carbon atoms, and these hydrocarbon groups have a part of their hydrogen atoms other than hydrogen atoms. The functional group may be substituted.

In the imino group (Y-2) represented by the general formula (5), R ² and R ³ include the same hydrocarbon group as R ^1, and these hydrocarbon groups are the same as R ¹ , Some may be substituted with other functional groups.

  Examples of the imino group (Y-2) represented by the general formula (5) include a methylimino group.

In General Formula (6), R ⁴ represents a hydrocarbon group having 1 to 36 carbon atoms, or a residue obtained by removing one hydroxyl group from a polyhydric alcohol or sugar.
In this hydrocarbon group, part of the hydrogen atoms may be substituted with another functional group such as a functional group selected from the group consisting of hydroxyl group, methoxyl group, ethoxyl group, nitro group and hydroxyphenyl group.

In the ester group (Z-1) represented by the general formula (6), when R ⁴ is a hydrocarbon group having 1 to 36 carbon atoms, the hydrocarbon group includes the same hydrocarbon group as R ^1. It is.
When R ⁴ is a hydrocarbon group having 1 to 36 carbon atoms, among these hydrocarbon groups, a linear aliphatic hydrocarbon group is preferable from the viewpoint of durability of washing and durability of enzyme activity. A methyl group and an ethyl group are preferable, and an ethyl group is most preferable.

Examples of the polyhydric alcohol include divalent to trivalent alcohols, and examples thereof include ethylene glycol, propylene glycol, diethylene glycol, and glycerin.
Examples of the sugar include glucose, sucrose, sorbitol, mannitol and trehalose.

In General Formula (7), R ⁵ represents a hydrogen atom or a hydrocarbon group having 1 to 36 carbon atoms, and in this hydrocarbon group, a part of the hydrogen atom is substituted with another functional group other than a hydrogen atom. May be.

In the N-alkylamide group (Z-2) represented by the general formula (7), when R ⁵ is a hydrocarbon group having 1 to 36 carbon atoms, the hydrocarbon group may be the same carbon atom as R ^1. A hydrogen group is included, and these hydrocarbon groups may be partially substituted with other functional groups in the same manner as R ¹ .
When R ⁵ is a hydrocarbon group having 1 to 36 carbon atoms, among these hydrocarbon groups, a linear aliphatic hydrocarbon group is preferable from the viewpoint of durability of washing and durability of enzyme activity. A methyl group and an ethyl group are preferable, and a methyl group is most preferable.

  When the arginine derivative or a salt thereof (B-2) is a salt of an arginine derivative, an inorganic acid salt (hydrochloride, borate, phosphate, pyrophosphate, sulfate, silicate, etc.) and an organic acid salt ( Formate, acetate, oxalate, lactate, citrate, trimellitic acid and pyromellitic acid).

  Specific examples of the arginine derivative or a salt thereof (B-2) include N-acetylarginine ethyl ester hydrochloride.

The guanidine derivative or a salt thereof (B-3) is not particularly limited, but specifically, aminoguanidine (—NH ₂ ), dicyandiamide (—CN), guanylthiourea (—C (═S) NH ₂ ), dodecyl guanidine (—C ₁₂ H ₂₅ ), ethyl guanidine (—C ₂ H ₅ ), octyl guanidine (—C ₈ H ₁₇ ) and biguanide (—C (═NH) NH ₂ ). Here, () represents Q.

  Of these, (B-1) and (B-2) are preferable, and (B-2) is more preferable, and particularly preferable from the viewpoints of durability of detergency and enzyme activity. Is N-α-acetylarginine ethyl ester hydrochloride.

The content (% by weight) of the compound (B) contained in the medical device cleaning agent of the present invention is from 0 to 0% relative to the weight of the medical device cleaning agent from the viewpoints of durability of cleaning and enzyme activity. 01-30 are preferable, More preferably, it is 0.03-10, Next, more preferably, it is 0.05-5.
The content of the compound (B) contained in the cleaning agent for medical devices of the present invention is 1 to 1000% by weight with respect to the weight of the enzyme (a), from the viewpoint of durability of detergency and durability of enzyme activity. It is preferably 5 to 500% by weight, more preferably 10 to 300% by weight.

  The cleaning agent for medical devices of the present invention may contain only the compound (A), but it may contain the compound (A) and the compound (B) from the viewpoint of durability of cleaning and durability of enzyme activity. preferable.

  When (A) and (B) are contained, the weight ratio of (A) and (B) (weight of (A) / weight of (B)) is preferably 0.1 to 9, more preferably 0.8. It is 2-8, Most preferably, it is 0.5-5.

  Examples of the enzyme (a) that is an essential component in the present invention include protease (a-1), amylase (a-2), lipase (a-3), and cellulase (a-4).

  The protease (a-1) includes those of animal, plant or microbial origin, and those of microbial origin are preferred from the viewpoint of availability. Chemically or genetically modified variants are also included. Among the proteases, serine proteases are preferable from the viewpoint of sustained effect, and specifically, subtilisin, particularly those derived from Bacillus, such as subtilisin Novo, subtilisin Carlsberg, subtilisin 309, subtilisin 147 and subtilisin 168, and Trypsin (for example of porcine or bovine origin) and Fusarium protease, papain.

Commercially available protease, Novozymes Inc. ^{Alcalase TM, Savinase TM, Primase TM} , etc. Durazym ^TM and Esperase ^TM and Genencor Purafect ^TM and Purafect OXP ^TM and the like.

Amylase (a-2) includes those of bacterial or fungal origin. Chemically or genetically modified variants are also included. Examples of the amylase include B.I. described in detail in British Patent No. 1,296,839. Examples include α-amylase obtained from a special strain of B. licheniformis.
Commercially available amylases, Novozymes of Duramyl ^TM, Termamyl ^TM, include Fungamyl ^TM and BAN ^TM and Gist-Brocades Inc., Rapidase ^TM and Maxamyl P ^TM.

  Lipases (a-3) include those of bacterial or fungal origin. Chemically or genetically modified variants are also included. Examples of lipases include Humicola langinosa lipase (EP 258 068 and EP 305 216), Rhizomucor miehei lipase and Candida (Candida) Patent No. 238 023), C.I. Antactica lipase A and B, Pseudomonas lipase (European Patent No. 214 761), P. P. pseudoalcaligenes and P. pseudoalgegenes. P. alcaligenes lipase (EP 218 272), P. a. P. cepacia lipase (European Patent No. 331 376); P. stutzeri lipase, P. p. P. fluorescens lipase and Bacillus lipase (British Patent No. 1,372,034); B. subtilis lipase (Dartois et al. (1993), Biochemica et Biophysica Acta 1131, 253-260), B. stearothermophilus lipase (Japanese Patent Publication No. 64-744992) and B. stearothermophilus lipase. And B. pumilus lipase (WO 91/16422).

Commercially available lipases, Genencor M1 Lipase ^TM, Luma fast ^TM and Lipomax ^TM, include Novozymes of Lipolase ^TM and Lipolase Ultra ^TM and Amano Enzyme Inc. of Lipase P "Amano" ^TM.

  Cellulases (a-4) include those of bacterial or fungal origin. Chemically or genetically modified variants are also included. Cellulases include those disclosed in US Pat. No. 4,435,307 as fungal cellulases produced from Humicola insolens.

Commercial cellulases include Novozymes Celluzyme ^™ and Kao KAC-500 (B) ^™ produced by strains of Humicola insolens.

  Among the enzymes (a), protease (a-1) is preferable from the viewpoint of detergency.

  In this invention, the enzyme (a) contained in a cosmetic composition can contain 2 or more types. Examples of the combination containing two or more include a combination including two or more proteases, protease and amylase, protease and lipase, or protease, amylase and lipase.

  The content of the enzyme (a) contained in the medical device cleaning agent of the present invention is preferably 0.01 to 5% by weight, more preferably 0.8%, based on the weight of the medical device cleaning agent from the viewpoint of detergency. It is 05 to 3% by weight, particularly preferably 0.1 to 2% by weight.

  Water that is an essential component of the present invention is not particularly limited, and examples thereof include tap water, ion exchange water, distilled water, and reverse osmosis water.

  The content of water contained in the cleaning agent for medical devices of the present invention is 20 to 99.9% by weight with respect to the weight of the cleaning agent for medical devices, from the viewpoint of durability of cleaning and durability of enzyme activity. More preferably, 37 to 99.9% by weight, next more preferably 60 to 99% by weight, particularly preferably 65 to 97.9, particularly preferably 87 to 97.9% by weight, and most preferably 93 to 9% by weight. 95.

  In addition to the compounds (A), (B), the enzyme (a) and water, the medical device cleaning agent of the present invention includes a viscosity modifier (b), a surfactant (c), and a water-miscible organic solvent. (D), an inorganic salt (e), a sugar (f), an amino acid (g) other than arginine, a pH adjuster (h) and a preservative (i) can be contained.

  As the viscosity modifier (b), a known substance used in a cleaning agent for medical devices can be used, and examples thereof include cetylmethylcellulose (CMC).

  As surfactant (c), nonionic surfactant (c-1), anionic surfactant (c-2), cationic surfactant (c-3) and amphoteric surfactant (c-4) Is mentioned.

  As nonionic surfactant (c-1), aliphatic alcohol (carbon number 8-24) alkylene oxide (carbon number 2-8) adduct (degree of polymerization = 1-100) [oleyl alcohol ethylene oxide propylene oxide addition Product], aliphatic amine (carbon number 8-24) alkylene oxide (carbon number 2-8) adduct (degree of polymerization = 1-100) [hexadecylamine ethylene oxide propylene oxide adduct, laurylamine ethylene oxide adduct , Stearylamine ethylene oxide propylene oxide adducts, etc.], (poly) oxyalkylene (carbon number 2-8, polymerization degree = 1-100) glycol higher fatty acid (carbon number 8-24) ester [polyethylene glycol monostearate (polymerization) Degree = 20) and polyethylene distearate Recall (degree of polymerization = 30), etc., polyvalent (divalent to 10-valent or higher) alcohol fatty acid (carbon number 8-24) ester [glyceryl monostearate, ethylene glycol monostearate, sorbitan monolaurate, etc.], Multivalent (divalent to 10-valent or higher) alcohol higher fatty acid (8 to 24 carbon atoms) ester (poly) alkylene oxide adduct (2 to 8 carbon atoms of alkylene group, polymerization degree = 1 to 100) [sorbitan mono Laurate ethylene oxide (polymerization degree = 10) adduct and methyl glucose dioleate ethylene oxide (polymerization degree = 50) adduct, etc.], fatty acid N-hydroxyalkylamide [1: 1 type coconut oil fatty acid diethanolamide and 1: Type 1 lauric acid diethanolamide, etc.], alkyl (C1-22) (poly) o Sialkylene (2-8 carbon atoms, degree of polymerization = 1-100) phenyl ether, alkyl (8-24 carbon atoms) (poly) oxyalkylene (2-8 carbon atoms, degree of polymerization = 1-100) -aminoalkyl ( C8-24) -ether and alkyl (C8-24) dialkyl (C1-6) amine oxide [lauryl dimethylamine oxide etc.] etc. are mentioned.

  Examples of the anionic surfactant (c-2) include an alkyl ether carboxylic acid having 8 to 24 carbon atoms or a salt thereof and an alkyl (poly) oxyethylene ether carboxylic acid having 8 to 24 carbon atoms or a salt thereof [(poly) oxy Ethylene (degree of polymerization = 1 to 100) sodium lauryl ether acetate and (poly) oxyethylene (degree of polymerization = 1 to 100) disodium lauryl sulfosuccinate, etc.], alkyl sulfate salts having 8 to 24 carbon atoms and carbon numbers 8 to 8 24 alkyl (poly) oxyethylene sulfate esters [sodium lauryl sulfate, lauryl (poly) oxyethylene (degree of polymerization = 1-100) sodium sulfate and lauryl (poly) oxyethylene (degree of polymerization = 1-100) sulfate-tri Ethanolamine salts, etc.], palm oil fatty acid monoethanolamide sulfate sulfonate Lithium, alkyl phenyl sulfonates having 8 to 24 carbon atoms [sodium dodecylbenzene sulfonate, etc.], alkyl phosphate salts having 8 to 24 carbon atoms and alkyl (poly) oxyethylene phosphate salts having 8 to 24 carbon atoms [Sodium lauryl phosphate and (poly) oxyethylene (degree of polymerization = 1-100) sodium lauryl ether phosphate, etc.], fatty acid salt [sodium laurate, triethanolamine laurate, etc.], acylated amino acid salt [coconut oil fatty acid Methyl taurine sodium, coconut oil fatty acid sarcosine sodium, coconut oil fatty acid sarcosine triethanolamine, N-coconut oil fatty acid acyl-L-glutamic acid triethanolamine, N-coconut oil fatty acid acyl-L-glutamic acid sodium and lauroylmethyl-β -Alanine Sodium etc.].

  As the cationic surfactant (c-3), quaternary ammonium salt type [stearyl trimethyl ammonium chloride, behenyl trimethyl ammonium chloride, distearyl dimethyl ammonium chloride and ethyl lanolin sulfate fatty acid aminopropylethyl dimethyl ammonium etc.] and amine salts Type [diethylaminoethylamide stearate lactate, dilaurylamine hydrochloride, oleylamine lactate, etc.] and the like.

  As the amphoteric surfactant (c-4), a betaine-type amphoteric surfactant [coconut oil fatty acid amide propyldimethylaminoacetic acid betaine, lauryldimethylaminoacetic acid betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazoli Nium betaine, laurylhydroxysulfobetaine, lauroylamidoethylhydroxyethylcarboxymethylbetaine hydroxypropyl sodium phosphate, etc.] and amino acid type amphoteric surfactants [sodium β-laurylaminopropionate, etc.].

  As the surfactant (c), one type or two or more types can be used. When two or more types are used, combinations thereof include, for example, a nonionic surfactant and an anionic surfactant, a nonionic surfactant and a cationic surfactant, and a nonionic surfactant and an amphoteric surfactant. A combination etc. are mentioned.

As the surfactant (c), a nonionic surfactant is preferable from the viewpoint of detergency.
Among nonionic surfactants, aliphatic alcohols (8 to 24 carbon atoms), alkylene oxide (2 to 8 carbon atoms) adducts (degree of polymerization = 1 to 100), polyvalent (2 to 10 or more) Alcohol higher fatty acid (carbon number 8-24) ester (poly) alkylene oxide adduct (alkylene group 2-8, polymerization degree = 1-100), aliphatic amine (carbon number 8-24) ethylene oxide propylene oxide More preferred are adducts (degree of polymerization = 1-100) and alkyl (C8-24) dialkyl (C1-6) amine oxides.

  The water-miscible organic solvent (d) is not particularly limited as long as the solubility in 100 g of water is 10 g or more, and examples thereof include ethanol, isopropyl alcohol, glycerin, ethylene glycol, propylene glycol, and sorbitol.

  Examples of the inorganic salt (e) include sodium chloride, potassium chloride, sodium borate, calcium chloride, magnesium chloride, sodium formate, magnesium sulfate, and ammonium sulfate.

  Examples of the sugar (f) include trehalose, sucrose, dextrin, cyclodextrin, maltose, fructose, hyaluronic acid and chondroitin sulfate.

  Examples of amino acids (g) other than arginine include glycine, alanine, aspartic acid, asparagine, phenylalanine, tryptophan, tyrosine, leucine, lysine, histidine, and salts thereof.

  As the pH adjuster (h), a conventional pH adjuster can be used, and examples thereof include borate buffer, phosphate buffer, acetate buffer, Tris buffer, HEPES buffer, and citric acid.

  As the preservative (i), a conventional preservative can be used. For example, paraben, phenoxyethanol, sorbic acid, phenol and the like can be mentioned.

The content (% by weight) of the viscosity modifier (b) contained in the medical device cleaner of the present invention is preferably 0 to 5, more preferably 0, with respect to the weight of the medical device cleaner from the viewpoint of handling. ~ 1, then more preferably 0-0.5.
The content of the surfactant (c) contained in the medical device cleaning agent of the present invention is preferably 0 to 50% by weight, more preferably 2 to 2% with respect to the weight of the medical device cleaning agent from the viewpoint of detergency. It is 40% by weight, particularly preferably 5 to 30% by weight.
The content of the water-miscible organic solvent (d) contained in the medical device cleaning agent of the present invention is preferably 0 to 50% by weight with respect to the weight of the medical device cleaning agent from the viewpoints of detergency and enzyme activity. More preferably, it is 0 to 30% by weight, and particularly preferably 0 to 10% by weight.
The content (% by weight) of the inorganic salt (e) contained in the medical device cleaning agent of the present invention is preferably 0 to 40 with respect to the weight of the medical device cleaning agent from the viewpoint of detergency and enzyme activity. Preferably it is 0-30, then more preferably 0-20.
The content (% by weight) of the sugar (f) contained in the medical device cleaner of the present invention is preferably from 0 to 10, more preferably from the weight of the medical device cleaner, from the viewpoint of detergency and enzyme activity. Is 0-5, more preferably 0-3.
The content (% by weight) of amino acid (g) contained in the medical device cleaner of the present invention is preferably from 0 to 10, more preferably from the weight of the medical device cleaner, from the viewpoints of detergency and enzyme activity. Is 0-5, more preferably 0-3.
The content (% by weight) of the pH adjuster (h) contained in the medical device cleaner of the present invention is preferably 0 to 5 with respect to the weight of the medical device cleaner from the viewpoint of detergency and enzyme activity. More preferably, it is 0-3, Next more preferably, it is 0-1.
The content (% by weight) of the preservative (i) contained in the medical device cleaner of the present invention is preferably 0 to 5 with respect to the weight of the medical device cleaner from the viewpoint of detergency and enzyme activity. Preferably 0-3, then more preferably 0-2.

The cleaning agent for medical devices of this invention is obtained by mixing each component, and a manufacturing method is not specifically limited. An example is shown below.
(1) Add compound (A) and, if necessary, compound (B) to water and stir at 25 ° C. until uniform.
(2) A predetermined amount of components other than enzyme (a) is added and dissolved uniformly.
(3) Finally, enzyme (a) is added and dissolved to produce a cleaning agent for medical devices.

  In the present invention, the cleaning agent for medical devices refers to a wide range of medical devices such as an artificial dialysis device, an endoscope, and a dental treatment device, and parts such as a tube and a sealed container attached to the medical device. It is not a detergent for cleaning parts that need cleaning.

  The following examples further illustrate the invention, but the invention is not limited thereto.

<Production Example 1>
N-α-acetylarginine {Arginine acetamide, MP Bio Japan Co., Ltd.} 12.6 parts (0.05 mole part), 1 part of methanesulfonic acid and 92 parts (2 mole parts) of ethanol were mixed uniformly at 80 ° C. The mixture was heated and stirred for 5 hours, concentrated with an evaporator, and then neutralized by adding 5.2 parts (0.05 mol) of hydrochloric acid. Thereafter, it was recrystallized from water and dried under reduced pressure {60 ° C., 20 Pa} to obtain {N-α-acetylarginine ethyl ester hydrochloride}.

<Examples 1 to 14>
The medical agent cleaning agent of the present invention was prepared by blending at a rate of Table 1 at 25 ° C.

<Comparative Examples 1-7>
Compounding was performed at 25 ° C. in the proportions shown in Table 2 to prepare a cleaning agent for a medical device for comparison.

<Performance test>
<Measurement of enzyme activity>
The enzyme activity of the medical device cleaning agent was compared immediately after preparation of the medical device cleaning agent and after storage at 25 ° C. for 3 months.
10 μL of the medical device cleaning agent of Examples 1 to 14 or Comparative Examples 1 to 7 immediately after preparation in 5 mL of a Tris buffer solution of 0.5 wt% aqueous casein solution (the concentration of the Tris buffer in the solution is 50 mmol / L) In addition, it was left at 37 ° C. for 10 minutes. Thereafter, 5 mL of 15 wt% TCA solution (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and solid-liquid separation was performed with a centrifuge (15,000 rpm, 5 minutes, 4 ° C.). 1 mL of supernatant, 5 mL of 0.5 M aqueous potassium carbonate solution, and 1 mL of 3-fold diluted foreign reagent were added and left for 10 minutes.
The absorbance (A ₆₆₀ ) at ₆₆₀ nm of this solution was measured with a spectrophotometer.
Absorbance (A ′ ₆₆₀ ) was measured in the same manner as described above except that the medical device cleaning agent was stored at 25 ° C. for 3 months instead of immediately after preparation.
The persistence of enzyme activity was calculated by the following formula. The results are shown in Tables 1 and 2.

Persistence of enzyme activity = (A ′ ₆₆₀ ) / (A ₆₆₀ ) × 100

<Measurement of cleaning rate>
Horse-stored blood was separated into solid and liquid at 1,500 rpm for 10 minutes using a centrifuge, 40% by weight of the precipitate was uniformly mixed, and 20 μL was applied to a stainless steel plate (SUS430) to a size of 2 cm2, and a circulating dryer. And heat-denatured at 90 ° C. for 1 hour to prepare a contaminated plate.
First, the contaminated plate is immersed in ion-exchanged water at 40 ° C. for 10 minutes, and then ATP (adenosine triphosphate) in horse blood remaining without being washed into a stainless steel plate is colored with luciferase and quantified. This is a cleaning rate of 0%. On the other hand, a calibration curve was created by setting the ATP amount to 0 when the dirt was completely removed (washing rate 100%).
1 part by weight of the cleaning agent for medical devices of Examples 1 to 14 or Comparative Examples 1 to 7 immediately after production is dissolved in 100 parts by weight of ion-exchanged water, and the contaminated plate is immersed in this cleaning solution for 10 minutes, and then luciferase in the same manner as described above. The color was developed, and the washing rate (C ⁰ )% was calculated. The results are shown in Tables 1 and 2.
The cleaning rate (C ′)% was calculated in the same manner as described above after storage for 3 months at 25 ° C. instead of the medical device cleaning agent immediately after production. The results are shown in Tables 1 and 2.
The persistence of detergency was calculated by the following formula. The results are shown in Tables 1 and 2.

Persistence of detergency (%) = (C ′) / (C ⁰ ) × 100

The following compounds (A), compounds (B) and enzymes (a) in Tables 1 and 2 were used.
Guanidine hydrochloride: Wako Pure Chemical Industries urea: Wako Pure Chemical Industries arginine hydrochloride: Wako Pure Chemical Industries protease: Wako Pure Chemical Industries lipase: Wako Pure Chemical Industries amylase: Wako Pure Chemical Industries

From the results of the enzyme activity persistence in Tables 1 and 2, it can be seen that the medical device cleaning agents of Examples 1 to 14 have higher enzyme activity sustainability than the medical device cleaning agents of Comparative Examples 1 to 7. .
Moreover, from Table 2, in the cleaning agents for medical devices of Comparative Examples 1 to 4, although the cleaning rate against blood stains immediately after production is high, the cleaning rate is reduced after storage for 3 months at 25 ° C. It can be seen that the sustainability is low. Furthermore, in the cleaning agents for medical devices of Comparative Examples 5 to 7, the cleaning performance is high, but the cleaning rate is low immediately after production and after storage for 3 months at 25 ° C., and the cleaning performance is not sufficient.
On the other hand, in Examples 1-14 which are the cleaning agents for medical devices of this invention of Table 1, the washing | cleaning rate with respect to a blood stain is maintained high even after 3 months storage at 25 degreeC, and the sustainability of a cleaning property is high. I understand that.

  The medical device cleaning agent of the present invention can maintain the performance of the cleaning agent containing an enzyme. Therefore, it can be particularly suitably used as a cleaning agent for medical devices that require high cleanability.

Claims (5)

A cleaning agent for medical devices comprising at least one compound (A) selected from the group consisting of a compound represented by the following general formula (1) and a salt thereof, an enzyme (a) and water.

[Wherein, X represents an imino group, an oxygen atom or a sulfur atom. ] The cleaning agent for medical devices according to claim 1, wherein the enzyme (a) is a protease. The cleaning agent for medical devices according to claim 1 or 2, wherein the compound (A) is guanidine hydrochloride. Furthermore, the cleaning agent for medical devices in any one of Claims 1-3 containing the compound (B) represented by following General formula (2).

[Wherein, Q represents an amino group or an alkyl group, and a part of hydrogen atoms in the alkyl group may be substituted with a group other than a hydrogen atom. ] The cleaning agent for medical devices according to any one of claims 1 to 4, wherein the content of the compound (A) is 0.01 to 30% by weight based on the weight of the cleaning agent for medical devices.