CN109169653B - Cation composite disinfectant and application thereof - Google Patents
Cation composite disinfectant and application thereof Download PDFInfo
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- CN109169653B CN109169653B CN201811243879.7A CN201811243879A CN109169653B CN 109169653 B CN109169653 B CN 109169653B CN 201811243879 A CN201811243879 A CN 201811243879A CN 109169653 B CN109169653 B CN 109169653B
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- disinfectant
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
- A01N33/02—Amines; Quaternary ammonium compounds
- A01N33/12—Quaternary ammonium compounds
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/30—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests characterised by the surfactants
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
- A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
- A01N47/44—Guanidine; Derivatives thereof
Abstract
The invention provides a cationic composite disinfectant which can kill bacterial spores and can be used for space disinfection and sterilization and application thereof. The composite disinfectant comprises the following components in parts by weight: (1)0.05-5 parts of quaternary ammonium salt disinfectant; (2)0.05-5 parts of alkyl guanidine disinfectant; (3)0.05-5 parts of an amino acid type surfactant; (4) the balance of solvent; the composite disinfectant satisfactorily solves the problems that a single quaternary ammonium salt disinfectant or alkyl polyguanidine disinfectant cannot kill bacterial spores due to low activity and is not suitable for space sterilization. Meanwhile, as the quaternary ammonium salt and alkyl polyguanidine disinfectant used is mild in property, not only has no oxidation property, but also has no reducibility, and has no corrosivity on the surface of a disinfectant and sterilization space type object agent. Can be widely applied to disinfection or sterilization of various closeable spaces (such as operating rooms in hospitals, workshops in production enterprises, isolators, laboratories, biological safety cabinets and the like) and the surfaces of objects.
Description
Technical Field
The invention relates to the technical field of disinfection, in particular to a compound disinfectant consisting of a quaternary ammonium salt disinfectant, a guanidine disinfectant and an amino acid type surfactant and application thereof.
Background
Disinfectant (disinfectant) refers to a chemical agent used for killing pathogenic microorganisms on a transmission medium to make the transmission medium achieve the harmless requirement. Sporicide (sporicide) is a disinfectant that kills spores. The sporicides commonly used at present are classified mainly into peroxide sporicides (such as hydrogen peroxide, peroxyacetic acid and the like), active chlorine sporicides (such as hypochlorous acid/sodium, chlorine dioxide and the like), and aldehyde substances sporicides (such as formaldehyde, glutaraldehyde, o-phthalaldehyde and the like), and the method of atomizing or vaporizing is frequently used for space sterilization.
Part of the existing sporicide has oxidizability such as hydrogen peroxide, peracetic acid, active chlorine and other sporicides, and is relatively serious in corrosion; the other part has reducibility such as formaldehyde, glutaraldehyde, o-phthalaldehyde and the like, and causes serious pollution to the environment and too much toxicity, thereby limiting the application range of the compound.
Quaternary ammonium salt disinfectants have been of interest and research for nearly a hundred years as a class of mild cationic disinfectants. The water solution is neutral or alkalescent, and has the best sterilization effect when the pH value is 7-8.5; the action mechanism is that the bacteria belong to cations and are easy to be adsorbed on the surface of bacteria with negative charges, the permeability of a bacterial cell plasma membrane is changed, the bacteria are broken, and cytoplasmic substances are infiltrated outwards, so that the killing effect is achieved. At present, the disinfectant is not only used for skin mucosa disinfection, surgical hand washing disinfection and medical instrument disinfection in hospitals, but also used for disinfection of various public places and various production tools and equipment utensils, but has narrow antibacterial spectrum, is easy to generate drug resistance, and cannot kill bacterial spores when being used alone, so the disinfectant is not suitable for space sterilization.
Guanidine disinfectants are compounds having a disinfecting effect, and the general formula of the compounds is as follows: r1R2NC(＝NR3)NR4R5. Wherein R is1、R2、R3、R4、R5Represents H, alkyl and aryl. Guanidine disinfectants can be classified into alkyl groups and aryl groups in terms of substituents. In particular of the formula H2NC(＝NH)NR1R2Alkylguanidine derivative (R)1Is H, alkyl, R2Represents H, alkyl, C (═ NH) NH2、CONH2、C(S)NH2Etc.) are more favorable bactericides. The alkyl guanidine disinfectant is prepared into salt form, so that it is easy to dissolve in water, and is convenient for use, and at the same time, its antibacterial broad spectrum, low toxicity and sterilization range is more and more extensive, so that it can be used for sterilizing surface of hospital, food and alcoholic beverage industry, and also can be used for sterilizing fibre paper, etc. and sterilizing daily articles, such as towel, sweater and mask, etc.
Guanidine compounds can be classified into monoguanidine, biguanide, and polyguanidine disinfectants, in terms of the number of guanidine groups contained therein. Monoguanidine disinfectant means a compound containing only one guanidine group, such as: dodecyl guanidine acetate, which is named as dodine, has strong bactericidal capacity proved by the research of health organization, and is mainly used as a crop bactericide; octadecaguanidine acetate is used as pesticide, and is widely applied, and is widely used for disinfectants, industrial water treatment, women and children products, food packaging products, disinfection and sterilization treatment and the like. The main disinfectant used as biguanide disinfectant at present is: chlorhexidine aryl biguanide, polyethylene biguanide hydrochloride, chlorhexidine, etc. Have traditionally been used as bactericides in mouthwash. It is also widely used in surface disinfection in hospitals and food and alcoholic beverage industries, not only has good inhibition effect on gram-positive bacteria such as golden yellow glucose bacteria and the like, gram-positive bacteria such as escherichia coli and the like, and mould, but also has good inhibition effect on viruses, especially hepatitis B virus.
The polyguanidine disinfectant is an oligomer or a salt thereof, wherein the molecular structure monomer contains one or two guanidine groups, such as polyhexamethylene guanidine (cas:57028-96-3), poly [2- (2-ethoxy) -ethoxy ethyl ester ] guanidine (cas:374572-91-5), polyhexamethylene biguanide, poly (aminopropyl biguanide) and the like. Because the molecule of the antibacterial agent contains a polymer structure, the toxicity of the antibacterial agent is reduced, and the antibacterial agent has more excellent bactericidal effect, and is widely applied to various fields such as medical treatment and health, family life, food industry, livestock breeding and the like.
Guanidine disinfectants are similar to quaternary ammonium salt disinfectants, belong to two types of low-efficiency cationic disinfectants, have no effect of killing bacterial spores when being used alone, can only be used for disinfection, achieve the general requirements of disinfectants, and are not suitable for sterilization. However, the two disinfectants have the advantages of low toxicity, no stimulation to skin mucosa, no corrosion to metal fabrics, slight influence by organic matters, good stability and the like. The prior document reports that when the two disinfectants are compounded for use, the two disinfectants have certain synergistic effect [ Zhao Liu Chen and the like ], the single components of several cationic surfactants and the research on the sterilization performance of a composite system on pathogenic bacteria [ J ] printing and dyeing auxiliaries, 2017,34(5):24-29 ], but the document does not prove whether the two disinfectants have the effect of killing bacterial spores or not.
The amino acid type surfactants have the advantages of high safety to the environment and organisms, good compatibility with other various surfactants and the like, and particularly have good antibacterial performance and bactericidal performance for cationic and amphoteric amino acid surfactants. Lauroyl arginine ethyl ester hydrochloride (LAE) prepared from arginine and lauroyl is a cationic amino acid surfactant, has good antibacterial effect on gram-positive bacteria, gram-negative bacteria, pathogens, yeast and mould, can be used in meat food and poultry food, and has no toxic effect on human body. N-alkylglycine amphoteric surfactant prepared by reacting N-alkylamine with chloroacetic acid, namely telogo (Tego) amphoteric surfactantThe amino acid type surfactant is also an amino acid type surfactant with strong bactericidal capability, has good bactericidal property, foamability and wettability, and has good thermal stability and low toxicity. Representative products such as Tego51 (C)8-18Reaction product of an alkyl ethylenediamine and chloroacetic acid), Tego103S (C)8-18Reaction product of alkyl diethylenetriamine with chloroacetic acid) and Tego2000 and Rewocid WK30 (C)10-16Reaction products of alkyl propylenediamine with chloroacetic acid, CAS No.139734-65-9), and the like. The scale-eliminating disinfectant has excellent effect of killing pyococcus, intestinal bacillus, etc. to fungus and virus, but no effect of killing bacterial spore. The prior literature reports that the tela-based amphoteric surfactant (Tego103S) and chlorfenapyr have certain synergistic effect when used in a compounding way [ Trirong et al, Tego103S and 1227 synergistic bactericidal effect research [ J]Daily chemical industry 1997,3:50-52, but this document does not demonstrate whether there is a killing effect on bacterial spores.
PCT international patent (WO2010/097639 EN 2010.09.02) discloses a "disinfectant composition comprising a biguanide compound" useful for killing bacterial endospores from a material, comprising one or more biguanide polymers, one or more additional active agents selected from the group consisting of mono-quaternary ammonium salts, and one or more additional active agents selected from the group consisting of one or more isothiazolone compounds, endospore-killing active, and said composition further comprising a polyorganosiloxane or a blend of polyorganosiloxanes, but the composition does not prove useful for steric sterilization.
PCT international patent (WO2010/000744 EN 2010.01.07) discloses that a cationic surfactant obtained by condensation of fatty acids and basic amino acid esters, in particular lauramide ethyl ester of arginine (LAE), in combination with another sporicidal sodium tripolyphosphate and polysorbate, can be used to treat objects infected with spores. This technique also does not prove useful for space sterilization.
Disclosure of Invention
In order to solve the problems of safety, effectiveness, corrosiveness and stability of the existing disinfectant (sporicide) in space disinfection and sterilization, the invention provides a cationic composite disinfectant (sporicide) which is stable, efficient and non-corrosive and has a good killing effect on bacterial spores and application thereof in space disinfection and sterilization.
The cation composite disinfectant comprises the following components in parts by weight:
(1)0.05-5 parts of quaternary ammonium salt disinfectant;
(2)0.05-5 parts of alkyl guanidine disinfectant;
(3)0.05-5 parts of amino acid type surfactant.
The sporicide provided by the invention satisfactorily solves the problems of corrosivity, instability and toxicity of the existing sporicide. Can be widely applied to the disinfection or sterilization of the surfaces of various objects and the closed space (such as operating rooms in hospitals, workshops in production enterprises, isolators, laboratories, biological safety cabinets and the like).
Preferably, the quaternary ammonium salt disinfectant is selected from C8-C18Single-chain or double-chain quaternary ammonium salt consisting of aliphatic chain and methyl, benzyl or ethyl benzyl and one or more of benzalkonium chloride pinine.
Preferably, the quaternary ammonium salt disinfectant is selected from one or a mixture of single-chain dodecyl dimethyl benzyl ammonium and double-chain didecyl dimethyl ammonium.
Examples of quaternary ammonium salt disinfectants of the present invention include, but are not limited to: dodecyl dimethyl benzyl chloride/ammonium bromide (benzalkonium chloride/bromide), dodecyl dimethyl phenoxyethyl ammonium bromide (domiphen), tetradecyl dimethyl pyridinium bromide, didecyl dimethyl chloride/ammonium bromide (thalidomide), octyl decyl dimethyl chloride/ammonium bromide, chloro/bis dodecyl dimethyl ethylene diammonium bromide, benzalkonium chloride pinine and mixtures thereof. The quaternary ammonium salt disinfectant has the advantages of low toxicity, safety, small side effect, low concentration, no color, no odor, low irritation and the like no matter used alone or in combination.
Examples of particularly preferred quaternary ammonium salt disinfectants include single-chain and double-chain mixtures, such as mixtures of dodecyl dimethyl benzyl chloride/ammonium bromide (single-chain, generation 1) with didecyl dimethyl chloride/ammonium bromide or octyl decyl dimethyl chloride/ammonium bromide (double-chain, generation 3) as generation 4 in a ratio of 1:2-2:1, which are lipophilic, functionally complementary, have 1-2 log enhanced bactericidal activity over a single disinfectant, have an extended life cycle, are chemically stable, less corrosive, and are less affected by the hardness of organic matter and water; meanwhile, the sterilization activity can be enhanced by preventing the cells from generating drug resistance, and the sterilization range is enlarged. For example, the mixture of dodecyl dimethyl benzyl ammonium chloride (single chain) and didecyl dimethyl ammonium chloride (double chain) with the ratio of 4:6 can reach the killing rate of 99.99 percent when the concentration is 250ppm and the action is carried out for 30 seconds on staphylococcus aureus and escherichia coli; for black variant spores of bacillus subtilis, 12500mg/L, action time is 10min, 6250mg/L and action time is 20min, the killing rate is 99.86%, but the killing rate is difficult to reach 99.999% (6 logarithm of spores are killed), while the single-component didecyl dimethyl ammonium chloride kills the black variant spores of bacillus subtilis, and when the effective concentration is 4000mg/L, the action time is 5h, and the killing rate is only 95%. Therefore, the combination of several quaternary ammonium salts can only enhance the antibacterial activity of the quaternary ammonium salts to a limited extent, but the invention proves that the quaternary ammonium salts have the effect of killing spores when being combined with the alkyl guanidine disinfectant and the amino acid type surfactant.
Preferably, the alkyl guanidine disinfectant is selected from oligomeric guanidine disinfectants containing one or two guanidine groups in the molecular structure, and preferably is one or a mixture of several selected from polyhexamethylene guanidine, polyhexamethylene biguanide and poly- [2- (2-ethoxy) -ethoxyethyl ] guanidine. The alkyl guanidine disinfectant has the advantages of broad antibacterial spectrum, low toxicity, wide sterilization range and the like whether used alone or in combination.
The alkyl guanidine disinfectant can be used independently or compounded with other types of bactericides. The system is effective at a pH of 4-10, and is soluble in nonionic surfactant, glycol ether, EDTA and most strong acids. Compared with quaternary ammonium salt disinfectant, the disinfectant has less smell and less foam, and the active components are stable to heat and non-volatile. As the disinfectant, the concentration of the disinfectant is generally 2 g/L-45 g/L. The disinfectant has broad bactericidal spectrum on bacterial propagules and strong bacteriostatic action. The composition has no harm to various materials, no corrosion, low toxicity, degradability and little influence on the environment, but the single component basically has no killing effect on bacterial spores and can only inhibit the propagation of the bacterial spores. If the polyhexamethylene biguanide hydrochloride disinfectant containing 1800mg/L acts on escherichia coli in the suspension for 5min, the average killing rate is 99.95 percent; the disinfectant containing 5000mg/L polyhexamethylene guanidine hydrochloride has an effect on bacillus subtilis var niger spores for 4 hours, and the average killing rate is 99.66%; when the polyhexamethylene monoguanidine and other guanidine are combined according to the proportion of 1:4-4:1, the antibacterial activity of the polyhexamethylene monoguanidine is also improved to a certain extent, for example, the minimum inhibitory concentration value of the poly- [2- (2-ethoxy) -ethoxyethyl ester ] guanidine to escherichia coli is 8-32mg/L, and when the polyhexamethylene monoguanidine is combined according to the proportion of 3:1, the minimum inhibitory concentration value of the poly- [2- (2-ethoxy) -ethoxyethyl ester ] guanidine is 1-8mg/L, so that the combined result of the plurality of guanidine disinfectants is similar to the combined result of the plurality of quaternary ammonium salt disinfectants, the antibacterial activity of the plurality of guanidine disinfectants can be enhanced only to a limited extent, and the effect of killing. However, when the alkyl guanidine disinfectant disclosed by the invention is combined with quaternary ammonium salt and amino acid type surfactant, the disinfectant has a spore killing effect.
Preferably, the amino acid type surfactant is selected from cationic amino acid surfactants, such as lauroyl arginine ethyl ester hydrochloride (LAE) prepared by taking arginine and lauroyl as raw materials, and research shows that the LAE has good bacteriostatic effect on gram-positive bacteria, gram-negative bacteria, pathogens, yeast and molds, can be used in meat food and poultry food, and has no toxic or side effect on human bodies.
Preferably, the amino acid type surfactant may also be selected from the group consisting of N-alkylglycine-based amphoteric surfactants prepared by reacting an N-alkylamine derivative with chloroacetic acid, i.e., telo-type amphoteric surfactants, such as those derived from C8-18Reaction product of an alkyl ethylenediamine with chloroacetic acid (trade name Tego51), from C8-18Reaction product of alkyl diethylenetriamine with chloroacetic acid (trade name Tego103) and a mixture of C10-16The reaction products of alkyl propylene diamines with chloroacetic acid (trade names Tego2000 and Rewocid WK30, CAS No.139734-65-9), the scale-off (Tego) class of amphoteric surfactants is also a class of surfactants havingThe amino acid type surfactant with strong bactericidal capacity has good bactericidal performance, foamability and wettability, good thermal stability and low toxicity. Has good effect of killing pyococcus, enterobacteria and the like on fungi and viruses, but has no effect of killing bacterial spores. The existing literature reports that the scale-removing amphoteric surfactant (Tego103) also has a certain synergistic effect when being used in combination with chlorfenapyr.
Specific examples of the amino acid type surfactant according to the present invention include, but are not limited to: LAE, Tego103, Tego51, Tego2000 and Rewocid WK30(CAS No. 139734-65-9). Preferred examples of the amino acid type surfactant according to the present invention are Tego103S, Tego2000 and LAE.
In order to make the solvent used in the disinfectant liquid of the invention quickly volatilize to generate faster disinfection and sterilization effects, the invention can select water and other volatile C besides purified water as the solvent2-C3A mixed solution composed of alcohol is used as a solvent; said C is2-C3The alcohol is selected from one or more of ethanol, n-propanol and isopropanol, and is used in a concentration capable of dissolving the components, preferably in a range of 0.1-99% (w/w), more preferably in a range of 1-50% (w/w) of the solvent.
The composite disinfectant of the present invention may contain other optional miscible substances, such as stabilizers, surfactants, corrosion inhibitors, wetting agents, fragrances, colorants, etc., in addition to the main components described above. These added mutual solubility materials are known in the art and do not chemically react or otherwise interfere with other ingredients already present. The amount of the compound to be added is not particularly limited as long as the required or prescribed residual level after sterilization is not increased or the sterilization effect is not lowered, depending on the kind of the substance to be added.
As a preferred embodiment of the invention, the cationic complex disinfectant comprises the following components in percentage by weight:
(1) 0.1-1% quaternary ammonium salt disinfectant
(2) 0.1-1% alkyl guanidine disinfectant
(3) 0.1-1% of amino acid type surfactant
(4) The balance of solvent;
the quaternary ammonium salt disinfectant is one or a mixture of dodecyl dimethyl benzyl ammonium chloride and/or didecyl dimethyl ammonium chloride; the alkyl guanidine disinfectant is polyhexamethylene (mono, di) guanidine and/or poly- [2- (2-ethoxy) -ethoxy ethyl ester]One or a mixture of more of guanidine; the amino acid type surfactant is one or a mixture of more of LAE, Tego2000 or Tego 103S; the solvent is water or water and C2-C3Mixed solution of alcohol.
As another preferred embodiment of the invention, the cationic complex disinfectant comprises the following components in percentage by weight:
(1) 0.1-0.5% of quaternary ammonium salt disinfectant, wherein the quaternary ammonium salt disinfectant is benzalkonium chloride or a mixture of benzalkonium chloride and didecyl dimethyl ammonium chloride in a weight ratio of 1:4-4: 1;
(2) 0.1-0.5% of an alkyl guanidine disinfectant, wherein the alkyl guanidine disinfectant is polyhexamethylene (mono, di) guanidine or a mixture of polyhexamethylene (mono, di) guanidine and poly- [2- (2-ethoxy) -ethoxyethyl ester ] guanidine, and the weight ratio of the polyhexamethylene (mono, di) guanidine to the poly- [ 4:1 is 1: 4;
(3) 0.1-0.5% of amino acid type surfactant, wherein the amino acid type surfactant is LAE or amino acid type surfactant with the weight ratio of 1:4-4:1, a mixture of Tego2000 and LAE;
(4) the balance of water or a mixed solution of ethanol and water.
The cation composite disinfectant can be prepared by the conventional preparation method in the field, and the final product is a transparent solution. When in use, the detergent can not be used with soap or other anionic detergents, and is not suitable for being used with iodine or peroxides (such as potassium permanganate, hydrogen peroxide, sulfanilamide powder and the like).
The invention also provides the application of the cationic composite disinfectant in disinfection of object surfaces and disinfection or sterilization of spaces.
The invention is realized by sterilizing quaternary ammonium saltsCompounding agent, alkyl guanidine disinfectant and amino acid type surfactant with disinfection and sterilization function, and selecting water or water and alcohol (C) with low carbon chain1-C3) The composite disinfectant (sporicide) prepared by using the mixed solution as a solvent has stronger disinfection and sterilization effects than a single type of disinfectant, and particularly has stronger effect of killing bacterial spores (wherein the spore killing effect is not generated when the single type or two types of disinfectants are compounded). The cation composite disinfectant (sporicide) prepared by the invention consists of 3 types of disinfectants, but does not contain oxidizing substances such as hydrogen peroxide, peroxyacetic acid, active chlorine and the like, so that the cation composite disinfectant is not corrosive; the cation composite disinfectant does not contain reducing substances such as formaldehyde, glutaraldehyde, o-phthalaldehyde and the like, does not cause serious pollution to the environment, and has no obvious toxic or side effect, so that the cation composite disinfectant (sporicide) is particularly suitable for disinfection or sterilization of surfaces of various objects and closable spaces (such as operating rooms of hospitals, workshops of production enterprises, isolators, laboratories, biosafety cabinets and the like) by adopting a spraying method as an optimization.
Compared with the sporicide product on the current market, the sporicide has the following characteristics:
(1) the disinfectant does not contain a large amount of strong electrolyte and oxidizing substances, so that the disinfectant has no obvious corrosion effect, is particularly suitable for disinfection or sterilization of surfaces of various objects and closable spaces (such as operating rooms in hospitals, workshops of manufacturing enterprises, isolators, laboratories, biosafety cabinets and the like) by adopting a spraying method;
(2) because the added disinfectants have the synergistic antibacterial effect, the disinfection and sterilization activity is improved, and the drug resistance is reduced.
Detailed Description
The raw materials used in the invention are known commercial products, such as dodecyl dimethyl benzyl ammonium chloride which can be purchased from Guangzhou special chemical company, and didecyl dimethyl ammonium chloride which can be purchased from Jinao chemical company, Inc., Anhui province; polyhexamethylene monoguanidine and polyhexamethylene biguanide are available from Shanghai high-polymer Biotech, Inc.; LAE is available from Shanxi Cheng Ri Biotech, Inc., Tego2000 or Tego103S is available from Guangzhou, Tuo Innovation chemical technology, Inc.
Examples 1-6 in Table 1 below are illustrative of the invention and are not intended to limit the scope of the invention. The properties were simultaneously compared with those of comparative examples 1 to 6 in Table 2. The concentration of each component refers to the mass percentage concentration.
TABLE 1 examples 1 to 6 consisting of 3 types of substances
TABLE 2 COMPARATIVE EXAMPLES 1-6 each consisting of 2 kinds of substances
Performance testing
1. Corrosion test on metals
The corrosion of the composite disinfectant (examples 1 and 2) of the present invention on metals (diluted with purified water to 0.5% concentration of active ingredient before the test) was tested with reference to the disinfection specification (2008) using carbon steel, stainless steel, copper and aluminum as test objects, and compared with the same concentration of polyhexamethylene guanidine (PHMG) and the same concentration of control 1, as follows:
respectively taking carbon steel, stainless steel, copper and aluminum, respectively, making into a product with a diameter of 24 + -0.2 mm and a thickness of about 1.0mm,
and a wafer with a small hole with the diameter of about 2.0mm is ground during the test, the surface oxide layer is measured, the diameter, the thickness and the aperture are measured, the surface area is calculated, and then the wafer is cleaned and dried for 1 hour at the temperature of 50 ℃. Weighing the mass, soaking in experimental solution (at a ratio of 20 ml/cm)2Liquid volume), 1 container was used for 1 metal, and the experimental solution was changed 1 time for 24 hours. Soaking for 72h, taking out the metal sheet, washing with distilled water, and drying at 50 deg.C for 1 h. Weighing immersionThe mass of the metal sheet after the bubble was measured, and the corrosion rate R (mm/a) was calculated from the mass loss.
[ R is corrosion rate, mm/a (mm/year); m is the weight of the metal sheet before the test, g; m istWeight of the sheet metal after the test, g; m iskFor chemical treatment to remove the weight loss value g of the corrosion product sample wafer, and for those without chemical removal treatment in the test, the formula is calculated by deleting mkA value; s is the total surface area (cm) of the metal sheet2) (ii) a t is test time, h; d is the density of the metal material in kg/m3。]
The test results are shown in Table 3. As can be seen from Table 3, the composite disinfectant (sporicide) of the present invention has the same corrosiveness to metals as the single-component or two-component disinfectant (comparative example 1), and has low corrosiveness to metals.
TABLE 3 Corrosion test results on metals
2. Space sterilization test and surface sterilization test
(1) Space sterilization test method and results
The cationic complex disinfectant prepared in examples 1 to 6 of Table 1 was subjected to a space sterilization test and simultaneously compared with the disinfectant prepared in comparative examples 1 to 6 of Table 1 in the following manner.
(I) Main Experimental materials
The dry heat sterilization biological indicator is characterized in that the bacteria content of the marked bacteria tablet is not less than 1.0 × 106CFU/tablet comprises Bacillus subtilis (ATCC9372) spore tablet and phenol red culture solution indicator tube, if the sterilization treatment is incomplete, the residual spore grows after the culture, the pH is reduced by acid production, the color of the culture solution changes from red to yellow, if the sterilization treatment is complete, the color of the culture solution remains unchanged (Nanjing shiso-called Biotech Co., Ltd.),
type-1 low-temperature vaporization nano-mist generator (provided by nano-mist science and technology limited, Wuhan city, with an atomization rate of 15ml/minThe disinfecting solution can be atomized into small particles of less than 1 micron).
Experimental space (II)
The height of a production workshop of a certain pharmaceutical enterprise is 2.8m, the width is 4.4m, the length is 6.5m, and the total volume of the space is about 80m3。
③ test method
The nano-mist generator is placed in the middle of a workshop, and spores are arranged on 4 wall surfaces and 4 corners of the workshop at the quantity of 106The biological indicator of CFU/tablet is 8 (numbering 1, 2, 3, 4, 5, 6, 7, 8 respectively), the height of the arranged biological indicator from the ground is 1m, then the tested sporicide or solution is added, all doors and windows are sealed, the machine is stopped after starting atomization for 80min, and the machine is kept stand for different time (about equal to atomization of 15 ml/m)3) Taking out the biological indicator (spore strip) according to an aseptic method, putting the biological indicator into spore culture solution with a corresponding number, placing the culture solution containing the bacillus subtilis strain pieces into a constant-temperature incubator at 30-37 ℃ according to the instruction of the purchased biological indicator, culturing for 48h, observing, taking 1 piece of the same batch of biological indicator as positive control, and if the color of the culture solution is changed from red to yellow after culturing for 48h, indicating that bacteria grow, judging that the sterilization is unqualified; if the red color still shows aseptic growth, and the positive control grows normally, the sterilization is judged to be qualified.
Experimental results
The results are shown in Table 4. As can be seen from Table 4, when the atomization volume was 15mL/m3When the sealing time is more than 60min, the composite disinfectant prepared according to the examples 1-6 in the table 1 has the capability of killing spores, and the comparative examples 1-6 prepared according to the table 2 and composed of 2 substances have no capability of killing spores. Therefore, the composite disinfectant is a sporicide and can be used for disinfecting and sterilizing spaces.
TABLE 4 results of space sterilization test of various examples and comparative examples
Note: indicator does not turn yellow after incubation, indicating sterile growth, marked-; indicating a yellow color after incubation, indicating bacterial growth, marked as +; 0/8 shows that all of the 8 biological indicators were aseptically grown; 8/8 shows that 8 of the 8 biological indicators have bacteria growing; the rest is analogized in the same way.
(2) Surface disinfection test method and results
Surface disinfection test method
The composite disinfectant (sporicide) prepared in example 1 of table 1 was subjected to a surface disinfection test: using atomization, 80m of the sporicide prepared in example 1 was used3The space is sterilized by nano mist, and the volume of the mist is 15ml/m3And the sealing time is 120 min. After the disinfection is finished, each surface in the sterilized clean area (2 points on each of 4 wall surfaces and 8 points on the ground are randomly selected) is wiped by using a sterile cotton swab, and the wiping area of each point is 5 x 5cm2After the rubbing, the head (cotton part) of the cotton swab was cut with sterile surgical scissors, and the cut cotton swab was put into a conical flask containing 50ml of 0.9% sterile sodium chloride solution, and sealed. The flask containing the sample was shaken repeatedly to release the microorganisms on the cotton swab into the solution. Filtering 50ml of film of the sample solution, taking out the filter membrane, enabling the bacteria face to face upwards, pasting the filter membrane on a TSA culture medium, culturing for 5 days at 30-35 ℃, counting and comparing with a detection result before sterilization.
② surface sterilization test results
The results are shown in Table 5, and it can be seen from Table 5 that: when the atomization volume is 15ml/m3When the sealing time is 120 minutes, the compound disinfectant (sporicide) can be used for space sterilization and can also be used for disinfecting the surface of an object, and after disinfection, surface microorganisms of walls, floors and equipment all meet the requirements of GMP (good manufacturing practice) environment.
TABLE 5 comparison of surface microbial contamination levels before and after Sterilization
In conclusion, the cationic composite disinfectant has stronger disinfection and sterilization capability than that of a disinfectant with a single component and that of a disinfectant with two components, and also has the capability of killing bacterial spores. The composite disinfectant satisfactorily solves the problems that a single quaternary ammonium salt disinfectant or alkyl polyguanidine disinfectant cannot kill bacterial spores due to low activity and is not suitable for space sterilization. Meanwhile, as the quaternary ammonium salt and alkyl polyguanidine disinfectant used is mild in property, not only has no oxidation property, but also has no reducibility, and has no corrosivity on the surface of a disinfectant and sterilization space type object agent. Can be widely applied to disinfection or sterilization of various closeable spaces (such as operating rooms in hospitals, workshops in production enterprises, isolators, laboratories, biological safety cabinets and the like) and the surfaces of objects.
As described above, the present invention is explained by the specific examples and embodiments based on the claims, but the present invention is not limited thereto. While the embodiments described in the claims can be implemented, various modifications that can be made by those skilled in the art are intended to fall within the scope of the present application.
Claims (3)
1. The cation composite disinfectant is characterized by comprising the following components in percentage by weight:
(1) 0.1-0.5% of quaternary ammonium salt disinfectant, wherein the quaternary ammonium salt disinfectant is a mixture of benzalkonium chloride and didecyl dimethyl ammonium chloride in a weight ratio of 1:4-4: 1;
(2) 0.1-0.5% of alkyl guanidine disinfectant, wherein the alkyl guanidine disinfectant is a mixture of polyhexamethylene guanidine and poly- [2- (2-ethoxy) -ethoxyethyl ] guanidine, and the weight ratio of the polyhexamethylene guanidine to the poly- [2- (2-ethoxy) -ethoxyethyl ] guanidine is 1:4-4: 1;
(3) 0.1-0.5% of amino acid type surfactant, wherein the weight ratio of the amino acid type surfactant is 1:4-4:1, a mixture of Tego2000 and LAE;
(4) the balance of 1-50% ethanol water solution.
2. The use of the cationic complex disinfectant of claim 1 for disinfecting or sterilizing spaces.
3. The use of the cationic complex disinfectant of claim 1 for disinfecting or sterilizing surfaces of objects.
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| CN111849233A (en) * | 2020-07-06 | 2020-10-30 | 中国科学院大学温州研究院(温州生物材料与工程研究所) | Super wear-resistant long-acting antibacterial and antiviral nano coating and preparation method thereof |
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| CN112205432A (en) * | 2020-09-27 | 2021-01-12 | 杭州氢态生物科技有限公司 | Cationic composite disinfectant based on plant antibacterial extract |
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| CN115119841A (en) * | 2022-07-29 | 2022-09-30 | 厦门兴勒贸易有限公司 | Novel chitosan composite cationic disinfectant suitable for high-power dilution |
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