JP2540777B2 - Liquid disinfectant - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention is used as a medical disinfectant for the purpose of sterilizing infection-causing bacteria related to medicine, such as prevention of nosocomial infections in hospitals, as well as for food-related use and for disinfection of livestock houses, and further. The present invention relates to a liquid disinfectant that can be used as a disinfecting sheet by impregnating it with wet tissue, absorbent cotton, non-woven fabric and the like.

[0002]

2. Description of the Related Art Nosocomial infection-causing bacteria that are problematic in the medical field are gram-positive cocci, Staphylococcus aureus, Enterobacteriaceae, Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus CNS, and methicillin-resistant Staphylococcus aureus. (MRS
As shown in A), the protagonist has changed over time.

As a medical disinfectant for preventing nosocomial infections,
(1) Strong bactericidal power, (2) Fast-acting, (3) Excellent sustainability (preferably at least 12 hours), (4) Low toxicity, and for humans and animals. Harmless, (5) No skin irritation, no bronchial irritation, (6) Stable without change in normal sunlight, temperature, etc. (7) No change in drug effect due to pH, acid, alkali, etc. The following conditions are required: (8) tasteless and odorless, (9) metal corrosion, and no fiber attack.

Further, as the site to which these medical disinfectants are applied, (1) in the skin system, fingers, skin, skin and mucous membrane of the surgical site, wound site, etc. (2) medical machines, instruments, Clothes, hats, masks, gowns, sheets, covers, etc. (3) Environmental systems include hospital rooms, floors, corridors, doorknobs, beds, tables, toilets, etc. As the form of the medical disinfectant applied to such various parts,
(1) For finger and skin disinfection, liquid or lotion,
(2) Liquid for dipping equipment, (3) Floor, corridor,
Liquid for the purpose of disinfecting the environment such as a room, and (4)
It must be liquid at the raw material stage even for spraying by using LP gas. As described above, the medical disinfectant must be liquid in any case.

At present, as disinfectants generally used in hospitals, alcohol-based disinfectants such as ethanol and isopropanol, phenol-based liquid phenols, phenol-based cresol soap solutions, benzalkonium chloride, benzethonium chloride, etc. Quaternary ammonium salt,
Iodine tincture, dilute iodine tincture, bovidone iodine, iodine such as iodine, chlorinated sodium hypochlorite, aldehydes such as formalin and glutaral, amphoteric surfactant alkylpolyaminoethylglycine hydrochloride, and piguanite chlorhexidine gluconate. Is.

[0006] However, each of the above-mentioned various agents conventionally used as a medical disinfectant has advantages and disadvantages, and those which can satisfy all the above-mentioned conditions required as a medical disinfectant are available. I can't find it.

For example, 60% of ethanol for disinfection
Although the ethanol solution before and after is used, this disinfecting ethanol rapidly kills the growing bacteria, but the spores are difficult to die, and Staphylococcus aureus, Escherichia coli, etc. live for about 1 hour or more, and they are fast-acting. There is no nature. Moreover, the boiling point is 7
It has a flash point of 8.3 ° C., a flash point of 128 ° C., and an evaporation rate of 230, which is not sufficient for sterilization, and there is a problem in terms of sustainability of the drug effect. Further, this disinfectant ethanol has a drawback that it cannot be used on mucous membranes or wounds because it irritates the skin. Also, isopropanol is twice as toxic as the disinfectant ethanol. In the case of phenol, it loosely binds to a bacterial protein and causes a protein denaturing action. Further, it has a strong permeability to cell membranes and causes functional deterioration and destruction of the membranes to kill the bacteria. However, although this phenol is effective against general bacteria and Mycobacterium tuberculosis, it has no effect against spore virus, and its usage has been reduced due to its unique odor and regulation by wastewater standards. Cresol soap solution is highly effective against Mycobacterium tuberculosis, has good permeability to organic substances, and is suitable for disinfecting feces and sputum. However, it is adsorbed by rubber, plastic, cloth, etc., and cannot be removed by washing with water, and there is a problem that the potency is reduced on the alkaline side. Quaternary ammonium salts such as benzalkonium chloride and benzethonium chloride are particularly strong bases and have specific bactericidal properties, but have no effect on spore viruses and tuberculosis bacteria, and are resistant to Gram-negative bacteria such as Pseudomonas aeruginosa There are some with. Furthermore, in the case of this quaternary ammonium salt, when it enters blood, it has a hemolytic action and causes a curare symptom. Also,
Human estimated oral toxicity LD50 = 30-400 mg / kg, rat oral toxicity LD50 = 400 mg / kg, mouse oral toxicity LD50
The toxicity is high at 340 mg / kg, and there are problems that allergic reactions, rashes of hypersensitivity, itching, etc. occur, and the presence of organic substances such as serum and pus, as well as soaps and alkalines are ineffective. In the case of iodine-based disinfectants such as iodine tincture, diluted iodine tincture, povidone iodine and iodine,
It has a broad antibacterial spectrum, low toxicity, and neutral to acidic properties with high bactericidal activity, but it has almost no effect when the brown color disappears in an alkaline solution, and it significantly decreases in the presence of organic substances such as blood and sputum. However, it has a stimulating effect on the skin and mucous membranes, and may cause acute dermatitis such as rash, blisters and pruritus, and may cause hypersensitivity. Sodium hypochlorite is often used as a disinfectant, but this one has a strong corrosive effect on metals and linens, and also roughens the skin, so hand disinfection cannot be performed. Formalin is mainly used in the gas disinfection method, but usually has a bactericidal effect only after a long time of 18 to 24 hours, and has no immediate effect. In the case of glutaral, general bacteria are killed in 1-2 minutes. As a usage method, it is necessary to use a container with a lid by a dipping method and to sufficiently perform post-water washing, and neither wiping nor spraying is performed. This glitaral is
Oral toxicity to mice LD50 =, which may affect central nervous system and cause dizziness, lethargy, ataxia, karen, etc.
250 mg / kg, rat oral toxicity LD50 = 311 mg /
The inhalation toxicity was 2.5 to 3 ppm inhalation in rats, which caused weight gain suppression and inflammation in the lungs and bronchi, and 6.0 ppm inhalation caused significant weight gain suppression, nose bleeding, ocular mucosal bleeding, and irritation. high. Alkylaminoethylglycine hydrochloride has the maximum efficacy as a bactericide near the isoelectric point (pH 8-9), but the efficacy decreases as the acidity and alkalinity become stronger, and the taste is very bitter, and it is not suitable for spraying. Not suitable. In addition, human estimated lethal dose = 3 g / kg,
The presence of protein reduces the bactericidal activity. Hand disinfection can cause severe skin irritation in people with hypersensitivity. Furthermore, in the case of chlorhexidine gluconate, the bactericidal activity varies considerably depending on the bacterial species, and some Gram-negative bacteria have low susceptibility,
Also, resistant strains appear much earlier. Mouse oral toxicity LD
50 = 2515 mg / kg, rat oral toxicity LD50 = 300
It is 0 mg / kg, and it causes rough skin when it comes into contact with the skin, and as a side effect, it causes allergic systemic symptoms such as skin rash, syncope, and dyspnea shock.

[0008]

As described above, at present,
What is used as a medical disinfectant has advantages and disadvantages in terms of bactericidal effect, its persistence, toxicity, etc., various application sites such as skin system, instrument meter, environmental system, dipping method, cleaning method. Applicable to all kinds of disinfection methods such as cleaning method, rubbing method, spray method, and satisfying all conditions required as a medical disinfectant such as fast-acting, sustaining drug efficacy, harmlessness and stability. There is nothing that can be done,
In particular, no excellent bactericide against the highly toxic MRSA is currently found. Therefore, the present invention is a liquid that can be applied to fingers, skin disinfection, immersion of instruments, environmental disinfection of floors, corridors, rooms, etc., and spraying using LP gas, etc. Strong and highly toxic MRSA
It is also effective against, has a fast-acting effect, is excellent in the duration of drug effect, and is tasteless, odorless, and has low toxicity and is harmless to humans, without skin irritation and bronchial irritation. Is exposed to normal sunlight, without the risk of corroding metals or attacking fibers.
It is stable and does not change with temperature, etc., and is used not only as a medical disinfectant, but also in other fields, such as food-related environmental disinfection of kitchens, dining rooms, etc., disinfection of tableware, food containers, etc. It is intended to provide a liquid disinfectant which can exert an excellent disinfecting effect for environmental disinfection, and by further impregnating wet tissue, absorbent cotton, non-woven fabric, etc. as a disinfecting sheet product. .

[0009]

In order to achieve the above object, the liquid disinfectant according to the present invention is constituted by adding paraoxybenzoic acid ester and alcohol, and further water to these.

The compounding amount of the paraoxybenzoic acid ester in the disinfectant is 0.01% or more. Also,
Alcohol is 5% or more, and the rest is water. If the content of the paraoxybenzoic acid ester is 0.01% or less, the desired sterilization and disinfection effects cannot be expected. Further, if the alcohol content is 5% or less, the solubility of the paraoxybenzoic acid ester, which is poorly soluble in water, decreases, and at the same time, it is difficult to expect an excellent bactericidal activity due to the synergistic action of the paraoxybenzoic acid ester and alcohol. Furthermore, in this case, the amount of water added is 2
It is 0% or more, preferably 50% or more. The reason is,
If the amount of water added is too small, the proportion of alcohol becomes high, and as a result, there is a problem in terms of irritation to the skin when this disinfectant is used for disinfecting fingers and skin.

Furthermore, by adding a moisturizing agent to the disinfectant obtained by adding the above-mentioned paraoxybenzoic acid ester, alcohol, and water to the disinfectant, the duration of the effect of the disinfectant and the irritation to the skin are improved. be able to. As the moisturizer, olive, orange, sesame, vegetable oil such as coconut, beef tallow, carnauba wax, paraffin, vaseline, stearyl stearate, or other polyhydric alcohols such as propylene glycol, dipropylene glycol, and tripropylene glycol, Wax-like products having film-forming properties can also be used, and among these, propylene glycol having a large affinity for the main ingredient, paraoxybenzoate, is preferred.

As described above, in the present invention, paraoxybenzoic acid ester is used as the main ingredient of the disinfectant, and as the paraoxybenzoic acid ester, methyl ester,
Ethyl ester, propyl ester, butyl ester,
Benzyl ester, isobutyl ester, isopropyl ester and the like are preferably used, and two or more of them can be used in combination. Among these esters, it is particularly preferable to use butyl ester, which has low toxicity to humans and animals and has high bactericidal activity.

Examples of alcohols used in combination with the above-mentioned paraoxybenzoic acid ester include ethanol and isopropanol. From the viewpoint of toxicity, it is more preferable to use ethanol.

When the liquid disinfectant of the present invention is used for spraying, the liquid disinfectant as described above and LP gas may be mixed in a ratio of about 1: 1 before use.

[0015]

Among the paraoxybenzoic acid esters used in the liquid disinfectant according to the present invention, paraoxybenzoic acid esters such as methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate and butyl paraoxybenzoate are existing chemical substances. No. 3-1585, Japanese Pharmacopoeia, Japanese Standards for Food Additives, Cosmetics Raw Material Standards, etc., it is widely known, and its solubility in water at 25 ° C. is 0.25 for methyl ester and 0.1 for ethyl ester.
7, propyl ester is 0.05, butyl ester is 0.02, and the melting point is methyl ester is 125
~ 128 ° C, 116-118 ° C for ethyl ester, 95-98 ° C for propyl ester, 69-for butyl ester
The temperature is 72 ° C., and both are colorless crystals or white crystalline powder. These paraoxybenzoates are
Acute oral toxicity (LD-50) in mice was 7800 (mg / kg) for methyl ester and 5000 for ethyl ester.
(Mg / kg), propyl ester 8000 (mg / kg
kg) and butyl ester are as low as 17,000 (mg / kg), and in terms of subacute toxicity, these four types of paraoxybenzoic acid esters are each 0.9 to 1.2.
As a result of breeding by administering g / kg / day for 96 weeks (for 2 years), no effect on growth was observed and toxicity to humans and animals was extremely low. Therefore, conventionally in the food field, soy sauce, vinegar, soft drinks, preservatives such as fruit epidermis, also in the field of cosmetics, quasi drugs, preservatives such as shampoo, rinse, lotion, In the pharmaceutical field, it is used as a preservative such as ointments and syrups. In addition, these para-oxybenzoic acid esters are characterized in that their efficacy and durability are not affected by pH.

The antibacterial properties of the above-mentioned paraoxybenzoic acid esters against fungi (minimum growth inhibitory concentration mg / kg) are shown in Table 1 below.

[0017]

[Table 1]

The antibacterial properties against bacteria (minimum inhibitory concentration mg / kg) are shown in Table 2 below.

[0019]

[Table 2]

As is clear from the comparison between Tables 1 and 2, these paraoxybenzoic acid esters have a great effect on fungi, but the effect on bacteria is about one-tenth that of fungi. On the other hand, for example, in the case of phenol-based o-phenylphenol (OPP), which is known as a preservative for the surface of fruits, it is 7500 to 1 / 10,000 against Staphylococcus aureus and 500 to 10000 against Escherichia coli. It can be sterilized by 1 in 7500 and 1 in 10,000 to 12500 against black mold,
Also, in the case of chlorhexidine, it can be sterilized by 1 in 1,000,000 against Staphylococcus aureus, 1 in 100,000 against E. coli, and 1 in 300,000 against Pseudomonas aeruginosa. Further, in the case of the quaternary ammonium salt, the carboxylic acid coefficient is about 300 to 400. Thus, in the case of paraoxybenzoic acid ester, the bactericidal activity against bacteria is greatly inferior to other disinfectants.

Further, as described above, the disinfectant is generally used for disinfecting fingers and skin by (1) swab method (cleaning method), scrub method (cleaning method), rubbing method (rubbing method), etc. About the thing, it is liquid or lotion-like, (2) It is also liquid when disinfecting instruments by swab method (wiping method), basin method (immersion method), etc. (3) In-hospital floor, Similarly, in the case of environmental disinfection in a corridor, a room, etc., it is also liquid, and (4) it is also liquid for spraying using LP gas or the like. That is, it is a condition that a disinfectant that is generally used, including medical products, is liquid. However, in the case of paraoxybenzoic acid ester, since it is a white crystalline powder having a low solubility in water as described above, it was unsuitable as a medical disinfectant. Therefore, conventionally, these paraoxybenzoic acid esters are simply the foods as described above,
It has been used only as an antiseptic in cosmetics and has not been used as a disinfectant at all.

On the other hand, in the present invention, in the conventional case,
By using paraoxybenzoic acid ester in combination with alcohol, the use of which as a disinfectant was not considered from the viewpoints of bactericidal property and low solubility in water, (1) Gram-negative bacteria Escherichia coli, It can sterilize positive bacteria Staphylococcus aureus, Pseudomonas aeruginosa, etc. quickly and in a small amount. (2) It can be used as a disinfectant as a liquid by being dissolved in alcohol. Furthermore, by adding water in addition to the paraoxybenzoic acid ester and alcohol, the skin irritation caused by alcohol when used for finger and skin disinfection can be alleviated.

Further, the liquid disinfectant prepared by adding the above-mentioned paraoxybenzoic acid ester, alcohol, and water to it is not particularly problematic when it is used for dipping, but the swab method (cleaning method) and the scrub method ( When finger, skin, or environmental disinfection is performed by a washing method), a rubbing method (rubbing method), or the like, white crystals of paraoxybenzoic acid ester may be precipitated after water and alcohol are dried and evaporated. Therefore, when used for these purposes, in addition to the above-mentioned paraoxybenzoic acid ester, alcohol, and water, fats, waxes, polyhydric alcohols, and the like may be used together as a moisturizing agent to form a film. Even after water and alcohol are dried and evaporated, the film formation can prevent the deposition of paraoxybenzoic acid ester and protect the skin to prevent skin irritation and rough skin.

[0024]

EXAMPLES Hereinafter, specific examples of the liquid disinfectant according to the present invention will be shown, but the present invention is not limited to these examples.

Example 1 According to the formulation shown in Table 3, butyl paraoxybenzoate (manufactured by Yoshitomi Pharmaceutical Co., Ltd.) was dissolved in ethanol, and water was further added to this to prepare the liquid disinfectants 1 to 1 according to the present invention. 4 was prepared.

[0026]

[Table 3]

(Experiment 1) The liquid disinfectants 1 to 4 according to the present invention prepared in Example 1 were subjected to a bactericidal effect test against bacteria. The test was conducted after adding Escherichia coli or methicillin-resistant Staphylococcus aureus (MRSA) to the disinfectant,
The viability of the fungus was determined over time. The results are shown in Table 4. still,
In the table, "+" indicates that the bacterium did not die, and "-" indicates that the bacterium did die.

The test method is as follows. 1) Test strain E. coli: Escherichia coil IFO 3301 MRSA: Methicillin Resistant Staphylococcus aur
eus (Kyoto Institute of Microbiology) 2) Test medium Subculture medium: Ordinary broth with 0.2% meat extract (Eiken Kagaku) Post-culture medium: SCDLP medium (Nippon Pharmaceutical Co., Ltd.) 3) Preparation of bacterial solution After subcultured 3 to 4 times using the subculture medium, the cells were transplanted to the same medium and cultured at 35 ° C. for 24 hours. 4) Test operation 1 ml of the bacterial solution was added to 10 ml of the disinfectant, mixed, and then allowed to act at 20 ° C. for a certain period of time. After 30 seconds and 1 minute from the start of the action, 1 platinum loop amount was transplanted from the action test tube to the post-culture medium, and at 2 ° C at 2 ° C.
After culturing for a day, the presence or absence of growth of the test bacterium was observed to determine whether the bacterium was alive or dead. As a control, sterilized water was also tested.

[0029]

[Table 4]

As is clear from the results shown in Table 4, all of the liquid disinfectants 1 to 4 according to the present invention have an excellent bactericidal activity against Escherichia coli and MRSA, and particularly 30 against MRSA. It could be completely killed within a short time within a second, and the rapid-acting property and excellent bactericidal property were revealed.

(Example 2) With the formulation shown in Table 5, various paraoxybenzoic acid esters were dissolved in ethanol or propylene glycol, and water was further added thereto to prepare liquid disinfectants 5 to 10 according to the present invention. did.

[0032]

[Table 5]

(Experiment 2) For the liquid disinfectants 5 to 10 according to the present invention prepared in Example 2, E. coli and methicillin-resistant Staphylococcus aureus (MR) were prepared in the same manner as in Experiment 1.
A bactericidal effect test against SA) was performed. The results are shown in Table 6. In addition, "NT" in the table indicates that the test was not conducted.

[0034]

[Table 6]

As is clear from the results shown in Table 6, the disinfectant according to the present invention is excellent against Escherichia coli and MRSA in all cases where methyl ester, ethyl ester and propyl ester are used as paraoxybenzoic acid ester. In addition, the paraoxybenzoic acid ester has a sufficient bactericidal power at 0.05%, and further has an excellent bactericidal power even when dissolved in propylene glycol alone without using ethanol. .

(Example 3) With the formulation shown in Table 7, various paraoxybenzoic acid esters were dissolved in ethanol or propylene glycol, and water was added thereto to prepare liquid disinfectants 11 and 12 according to the present invention. .

[0037]

[Table 7]

(Experiment 3) The liquid disinfectants 11 and 12 according to the present invention prepared in Example 3 were used as MRSA as a preserved strain of Japan Food Analysis Center (Methicillin Re).
A bactericidal effect test against Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) was performed in the same manner as in Experiment 1 except that sistant Staphylococcus aureus NS462) was used. Table 8 shows the results.

[0039]

[Table 8]

(Example 4) 0.2% butyl paraoxybenzoate (manufactured by Yoshitomi Pharmaceutical Co., Ltd.), 70% ethanol, 0.2% propylene glycol (manufactured by Kao Corporation), and 30% water. The disinfectant 13 according to the present invention was prepared.

(Experiment 4) About 3 ml of the above-mentioned disinfectant 13 was rubbed on a finger (rubbing method), and the number of bacteria on the finger before and 1 minute after disinfection was measured according to the streak plate method.
The results are shown in Table 9.

[0042]

[Table 9]

As is clear from the results shown in Table 9, the disinfectant 13 according to the present invention has fast-acting properties and excellent bactericidal properties.

[0044]

INDUSTRIAL APPLICABILITY As described above, the liquid disinfectant according to the present invention comprises paraoxybenzoic acid ester, alcohol, and water further added to these, and by using the paraoxybenzoic acid ester and alcohol in combination, Escherichia coli can be obtained. , Has excellent bactericidal properties against Staphylococcus aureus, Pseudomonas aeruginosa, and fast-acting. Especially, it is about 30 seconds even for MRSA, which is extremely toxic and has conventionally been said to have no suitable bactericide. It can be completely sterilized within a short time, and is extremely useful when used as a medical disinfectant.
Moreover, the paraoxybenzoic acid ester used in this disinfectant has a melting point of 70 ° C. or higher, does not soften at room temperature, does not decompose by sublimation, and is hardly soluble in water. Even after the water or water has dried, there is little loss of the chemicals due to washing, and the bactericidal effect is excellent in sustainability. And this disinfectant is tasteless, odorless, and
It has low toxicity and is harmless to humans and animals. At the same time, it does not irritate the skin, bronchi, etc., and does not corrode metals or damage fibers. Furthermore, in addition to the above disinfectant composition, by further adding a moisturizer, this moisturizer can protect the skin and reduce the irritation of the skin and mucous membranes caused by alcohol. It can also be applied to mucous membranes, etc., and at the same time, the film-forming action of a moisturizer can prevent whitening due to precipitation of crystals of paraoxybenzoic acid ester after evaporation of water and alcohol, and further improve the sustainability of medicinal effects. it can.

Claims (12)

(57) [Claims] 1. Paraoxybenzoic acid ester 0.01%
A liquid disinfectant comprising the above and 5% or more of alcohol and 20% or more of water. 2. Paraoxybenzoic acid ester 0.01%
A liquid disinfectant comprising the above, 5% or more of alcohol, 0.1% or more of moisturizing agent, and 20% or more of water. 3. The paraoxybenzoic acid ester is methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate,
The liquid disinfectant according to claim 1 or 2, which is one kind or two or more kinds selected from benzyl paraoxybenzoate, isopropyl paraoxybenzoate, and isobutyl paraoxybenzoate. 4. The liquid disinfectant according to claim 1 or 2, wherein the paraoxybenzoic acid ester is butyl paraoxybenzoate. 5. The liquid disinfectant according to claim 1 or 2, wherein the alcohol is ethanol or isopropanol. 6. The moisturizing agent is one or more selected from olive oil, orange oil, sesame oil, coconut oil, beef tallow, carnauba wax, paraffin, petrolatum, stearyl alcohol stearate, and propylene glycol. Item 2. The liquid disinfectant according to item 2. 7. The liquid disinfectant according to claim 2, wherein the moisturizing agent is propylene glycol. 8. Paraoxybenzoic acid ester 0.5%,
Liquid disinfectant consisting of 70% ethanol and 30% water. 9. Butyl paraoxybenzoate 0.2-0.
Liquid disinfectant consisting of 5%, ethanol 50-70%, water 30-50%. 10. Butyl paraoxybenzoate 0.2-
0.5%, ethanol 40%, propylene glycol 1
A liquid disinfectant consisting of 0% and 49.5-49.8% water. 11. Butyl paraoxybenzoate 0.2%,
Liquid disinfectant consisting of 70% ethanol, 0.2% propylene glycol, and 30% water. 12. A spray disinfectant comprising the liquid disinfectant according to any one of claims 1 to 11 and LP gas in a ratio of 1: 1.