JP3530981B2 - External sterilization method - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external sterilization method.
You. [0002] Conventionally, zinc white has a local astringent,
Moisture for the purpose of drying, protection, relief of irritation and absorption of secretions
It is used for the site of symptoms such as rash, dermatitis, abrasion, burn
You. Dosage forms include powders, liquids, oils, lotions
Preparations, liniments, ointments, pastes, plasters, etc.
Ointments are widely used in dosage forms. [0003] As an ointment, a zinc white ointment is available from the Japanese Pharmacopoeia.
Are listed, but no fungicides or preservatives are included.
Therefore, if used continuously for a long period of time, the affected area will be affected by bacteria, fungi, etc.
It has the disadvantage of being easily contaminated. [0004] Further, ittamol, acrinol, boric acid
Zinc white ointment is also known.
Ointments also have various disadvantages. In other words,
It is formulated for the purpose of flame and itching, but has a peculiar odor.
Color and black-brown color,
Hexinhua ointment is currently excluded from the Japanese Pharmacopoeia (12th revision)
Have been. Acrinol is also used for topical disinfection and disinfection.
Although it is formulated for the purpose, it sometimes causes irritation,
Easily discolored and yellowed clothing
ing. Furthermore, boric acid is formulated for the purpose of sterilization
But boric acid has only a weak stunting effect
That if it is used for a long time, it will be absorbed from the skin
May cause nausea, vomiting, diarrhea and other toxic symptoms,
Currently its use is regulated. [0005] Further, the above-mentioned zinc flower ointment containing various antibacterial agents is
Patients who are not safe, hypoallergenic and vulnerable to irritation
Was difficult to apply. [0006] The present inventor has set forth the present state of the art.
In view of the above, use a composition having excellent antibacterial and antifungal properties
We have been diligently researching to develop a new external sterilization method.
As a result, hinokitiol or its salt contains zinc white etc.
By using a composition containing a zinc compound, antibacterial
It was found that the properties and antifungal properties were significantly improved. Book
The invention has been completed based on such knowledge. That is, the present invention relates to a method for preparing a zinc compound and a hinokithio compound.
Characterized by using a composition containing
Pertaining to an external sterilization method. In the present invention, zinc compounds include
There is no limitation, and conventionally known ones can be widely used.
Zinc oxide, zinc chloride, zinc nitrate, zinc sulfate, phosphorous acid
Lead, zinc aluminate, zinc fluoride, zinc iodide, hydroxide
Lead, zinc carbonate, zinc chromate, zinc benzoate, acetate
Lead, zinc para-aminobenzoate, para-dimethylamino benzoate
Zinc perfume, zinc paraphenol sulfonate, paramethoki
Zinc cinnamate, zinc lactate, 2-mercaptopyridine-N
-Zinc oxide, zinc gluconate, zinc picrate,
Zinc enoate, zinc aspartate, zinc naphthenate, sa
Zinc lithate, zinc phenolsulfonate, sebacic acid
Zinc, sodium zinc tripolyphosphate, stearic acid
Lead, zinc caprate, zinc laurate, myristic acid
Lead, zinc palmitate, zinc oleate, polyphosphon
Zinc acid, chondroitin zinc sulfate, undecylenite
Lead, zinc ascorbate, zinc citrate, zinc pyrity
ON, hinokitiol zinc, zinc dipicolinate, zinc
Glycerolate complex, bizhistidine zinc complex, zinc-
Zinc complex such as 3,4-dihydroxybenzoic acid complex or the like
Is a zinc salt. In the present invention, these
One type of zinc compound may be used alone, or two or more types may be mixed.
They may be used in combination. In the present invention, the salt of hinokitiol is
For example, alkali gold such as sodium salt and potassium salt
Genus salts, alkaline earth metal salts such as magnesium salts, copper salts,
Inorganic salts such as metal salts such as zinc salts, diethanolamine
Salt, 2-amino-2-ethyl-1,3-propanediol
And alkanolamines such as triethanolamine salt
Salts, morpholine salts, piperazine salts, piperidine salts, etc.
Telocyclic amine salt, ammonium salt, arginine salt, lysine
Organic salts such as basic amino acid salts such as thiophene salts and histidine salts
And the like. Here as a basic amino acid
May be D-form, L-form or a mixture thereof. Book
In the invention, hinokitiol or a salt thereof is used alone.
Or a mixture of two or more. The zinc compound to be incorporated in the composition of the present invention
And the ratio of hinokitiol or a salt thereof
Is limited as long as the desired effect can be expressed.
The former: the latter is usually 0.0% by weight.
5 to 99.95: about 99.95 to 0.05, preferably
Is about 10-99.95: 90-0.05, most preferred
Or 50-99.9: 50-0.1
It is better to mix the ingredients. That is, a zinc compound and hinokithio
Of the zinc compound with respect to the total amount of the zinc compound or its salt.
About 05 to 99.95% by weight, preferably 10 to 99.95% by weight.
About 95% by weight, most preferably 50 to 99.9% by weight
Hinokitiol or its salt at 99.95-
About 0.05% by weight, preferably 90 to 0.05% by weight
Degree, most preferably about 50 to 0.1% by weight.
Is good. When the composition of the present invention is used as a medicine
A zinc compound and hinokitiol or a salt thereof.
Prepared and used as contained in a single pharmaceutical formulation
Each of which may be separately formulated and
Agents can also be used. Such preparations are commonly used
Fillers, extenders, binders, humectants, disintegrants, surface active
Prepared using diluents or excipients such as
You. Various forms of this pharmaceutical preparation are available depending on the purpose of treatment
Tablets, pills, powders
Preparations, solutions, suspensions, emulsions, granules, capsules, suppositories,
Injections (solutions, suspensions, etc.), oily ointments, emulsion ointments,
Water-soluble ointment, pasta, plaster, lotion, linime
External preparations such as paints and the like. Further, the composition of the present invention is used as a cosmetic.
Anti-dandruff, anti-acne, anti-axillary, bactericide
And / or can be added to cosmetics as preservatives, etc.
For example, preservation of cosmetics can be performed. The makeup
The ingredients include, for example, cleaning cosmetics, creams, emulsions,
Creams, cosmetic oils, basic cosmetics such as packs,
Foundation, lipstick, blusher, eyeliner, masker
Finish makeup for la, eye shadow, nail polish, white powder, etc.
Cosmetics for hair such as cosmetics, hair styling, hair nourishing, hair coloring, toothpaste,
Oral hygiene such as mouthwash, bath agent, whitening agent, sunscreen
It can be used in various forms such as
It can be manufactured according to a method commonly used in the field of
Wear. [0013] In addition, when producing such cosmetics,
Depending on the various known cosmetic bases, such as excipients, binding
Agents, lubricants, disintegrants, etc. can be used, further required
Various oils within a range that does not impair the effects of the present invention.
Fats, waxes, hydrocarbons, fatty acids, higher alcohols, esthetics
Oils, oily raw materials such as metal soaps, animal and plant extracts, and vita
Minerals, hormonal agents, medicinal agents such as amino acids, surfactant
Agents, pigments, dyes, pigments, fragrances, preservatives, bactericides, moisturizing
Agents, thickeners, antioxidants, sequestering agents,
Various known components and additives can be used in appropriate combinations
it can. When the composition of the present invention is used as a medicine,
The amount is not particularly limited as long as it has the efficacy effect
Is the total amount of the zinc compound and hinokitiol or a salt thereof.
Usually about 0.001 to 20% by weight, preferably 0.0
It is preferable to contain about 1 to 10% by weight. Also errand adjustment
Preparations for diluting preparations are usually 0.001 to 100
%, Preferably about 0.001 to 50% by weight
Good to be. Further, the composition of the present invention is used as a cosmetic.
In this case, it depends on the form, etc.
Although not limited to, generally zinc compounds and
Hinokitiol or a salt thereof is usually 0.0001 in total amount.
About 99.9% by weight, preferably 0.001 to 30 weights
It is preferable to contain about% by volume. In addition, the above cosmetics
Diluted with water, ethanol, olive oil or a suitable solvent
It can also be used. [0016] In molding into a tablet form, a carrier and
And various things that are well known in this field
Can be widely used. For example, milk
Sugar, sucrose, sodium chloride, glucose, urea, starch
, Calcium carbonate, kaolin, crystalline cellulose, silica
Excipients such as acid, water, ethanol, propanol, simple white
Cup, glucose solution, starch solution, gelatin solution, carbo
Xymethylcellulose, shellac, methylcellulose,
Binders such as potassium phosphate and polyvinylpyrrolidone;
Dried starch, sodium alginate, agar powder, lami
Naran powder, sodium bicarbonate, calcium carbonate, poly
Oxyethylene sorbitan fatty acid esters, lauryl
Sodium sulfate, monoglyceride stearate, starch
Disintegrants such as sugar, lactose, sucrose, stearin, cocoa
-, Disintegration inhibitors such as hydrogenated oils, quaternary ammonium salts
Group, absorption accelerators such as sodium lauryl sulfate, glycerin
Moisturizers such as starch and starch, starch, lactose, kaolin,
Adsorbents such as bentonite and colloidal silicic acid, purified tar
Corn, corn starch, wax, polyethylene glycol
A lubricant such as recall can be used. Need more tablets
Tablets coated with normal skin according to, such as sugar-coated tablets, gelatin
Coated tablets, enteric coated tablets, film coated tablets or
Heavy tablets and multilayer tablets can be used. When the pill is formed, the carrier and
Conventionally known ones in this field can be widely used. That
Examples include glucose, lactose, starch, cocoa
Fats, hardened vegetable oils, kaolin, talc and other excipients, arabi
Agum powder, tragacanth powder, gelatin, ethanol, etc.
Mixing agents, disintegrants such as laminaran and agar can be used
You. When molding into a suppository form, a carrier and
Conventionally known ones can be widely used. As an example
For example, polyethylene glycol, cocoa butter,
Alcohol, higher alcohol esters, gelatin, half
Synthetic glycerides and the like can be mentioned. When prepared as an injection, liquid preparations and emulsions
And suspending agents are preferably sterilized and isotonic with blood.
When forming into these forms,
Use everything that is commonly used in this field
For example, water, ethyl alcohol, macrogol, professional
Pyrene glycol, ethoxylated isostearyl alcohol
, Polyoxylated isostearyl alcohol, polyoxy
Can be used with ethylene sorbitan fatty acid esters
You. In this case, an amount sufficient to prepare an isotonic solution
Salt, glucose or glycerin in pharmaceutical preparations
May be used, and normal solubilizers, buffers,
A soothing agent or the like may be added. When prepared as an ointment,
In the field, conventionally known oil bases can be widely used,
Physically peanut oil, sesame oil, soybean oil, safflower
Oil, avocado oil, sunflower oil, corn oil, rapeseed
Oil, menz oil, castor oil, camellia oil, coconut oil, ory
Oils such as oil, poppy oil, cacao oil, tallow, lard, wool oil, etc.
(Particularly preferably lard), petrolatum, paraffin,
Mineral oils such as recon oil and squalane (especially white petrolatum
Preferred), isopropyl myristate, sailiso
Kutanoate, n-butyl myristate, isopropyl
Linoleate, propyl ricinoleate, isopropyl ricinate
Nolate, isobutyl ricinoleate, heptyl ricinole
, Diethyl sebacate, diisopropyl adipate
, Cetyl alcohol, stearyl alcohol, beheni
Alcohol, batyl alcohol, Kimyl alcohol,
Higher fatty acid esthetics such as beeswax, whale wax, and wood wax
, Higher fatty alcohols and waxes, stearin
Higher fatty acids such as acid, oleic acid and palmitic acid, carbon number
Mono-, di- and trig of 12-18 saturated or unsaturated fatty acids
Lyceride mixture (especially lipophilic glyceryl monostearate)
Phosphorus is preferred). In the present invention, these
One type of base may be used alone, or two or more types may be mixed.
May be used. The compositions of the present invention may contain conventional additives, for example,
Metal soap, animal or plant extracts, vitamins, formo
Medicines, pharmaceutical agents such as amine acids, surfactants, pigments, dyes,
Pigments, fragrances, UV absorbers, humectants, thickeners, antioxidants
Agents, sequestering agents, pH adjusters, etc.
It can be blended appropriately. The composition of the present invention can be produced by a conventional method.
You. The method of administration of the above pharmaceutical preparation is not particularly limited.
Formulation, patient age, gender and other conditions,
The drug is administered according to the degree of the disease. For example, tablets, pills
Preparations, solutions, suspensions, emulsions, granules and capsules
Is orally administered. In the case of injections,
Is mixed with normal replacement fluids such as glucose and amino acids
Administered intramuscularly, intradermally, subcutaneously as needed
Alternatively, it is administered intraperitoneally. Rectal administration for suppositories
Is done. In the case of an external preparation, it is applied to the affected area. The amount of the pharmaceutical preparation of the present invention used is usually
Active ingredients of zinc compounds and hinokitithio per day per adult
Or its salt at about 1-20 mg / kg body weight
It is recommended that the dose be administered in three divided doses. Use of the composition of the present invention in the field of external sterilization
The zinc compound to be incorporated into the composition of the present invention.
And the ratio of hinokitiol or a salt thereof
Is limited as long as the desired effect can be expressed.
Although not required, zinc compounds can be passed through the composition of the present invention.
Always about 0.00005 to 99% by weight, preferably 0.0
It is preferable to add about 01 to 30% by weight.
Ohl or its salt is usually about 0.00005-50% by weight
Degree, preferably about 0.001 to 20% by weight
Is good. When the composition of the present invention is used for external use,
Dilution can be appropriately performed as necessary. The composition of the present invention used for the purpose of external sterilization
In addition to the above-mentioned active ingredients, there are various conventionally known in the art.
Seed additives can be included. With such additives
For example, avocado oil, olive oil, coconut oil, cattle
Fats and oils such as lard, beeswax, whale wax, lanolin, etc.
Waxes, liquid paraffin, vaseline, squalane, sili
Hydrocarbons such as corn oil, lauric acid, myristic acid,
Fatty acids such as lumitic acid, stearic acid and oleic acid,
Cetyl alcohol, stearyl alcohol, 2-hexyl
Higher fats such as rudecanol and 2-octyldodecanol
Aromatic alcohols, isopropyl myristate, 2-oct
Chilled decyl myristate, cetyl isooctanoe
G, isononyl isononylate, dinonyl propylene group
Esters such as rechol, glyceryl monostearate
And glyceryl monooleate having 8 to 20 carbon atoms.
Mono-, di- or triglycerides of sum or unsaturated fatty acids,
Lower grades such as methanol, ethanol, and isopropanol
Alcohol, glycerin, propylene glycol, 1,
Many such as 3-butylene glycol and hexylene glycol
Polyhydric alcohols, water, various organic solvents, etc., metal soaps,
Animal or plant extracts, vitamins, hormones, amines
Etc., medicinal agents, surfactants, pigments, dyes, pigments, fragrances, purple
External absorbent, humectant, thickener, antioxidant, metal ion
Sequestering agent, pH adjuster, skin astringent, deodorant, bleach,
Examples include optical brighteners, builders, and various aerosol gases.
I can do it. In carrying out the method of the present invention,
The composition of the present invention is applied to a place requiring sterilization according to a conventional method.
And apply it. Such conventional means include, for example,
Play coating, brush coating, cloth rag, paper towel, cloth
To wipe with tissue, aerosol, etc.
Can be. The composition of the present invention requires external sterilization.
General or medical supplies (clothing, food, furniture, gauze,
Detergents, finishing glue, softeners, bleaching
It can be used by adding to an agent or the like. Further, the composition of the present invention is for external use
It can also be applied to animals or animal products that require sterilization. The composition of the present invention has excellent antibacterial activity and
It has antifungal activity and is effective against various bacteria and / or mold.
Various infectious diseases caused by, for example, atopic dermatitis, coins
Banknote dermatitis, self-sensitizing dermatitis, diaper dermatitis, stasis
Dermatitis such as atopic dermatitis, housewife (hand) eczema, dry eczema, etc.
Eczema, pustular psoriasis, boiling water, flushing from burns, tobihi, or
Blurring, burning, soreness, abrasion, secondary infection by scratching, etc.
It is particularly useful for the treatment of various skin diseases. Furthermore, the composition of the present invention has skin irritation,
Very low energy, baby, infant, child and other skin
Can be used for skin disease patients, for example, those who are sensitive to skin irritation.
Needless to say, mammals other than humans (such as dogs and cats)
And cattle, cattle, horses and other livestock).
Can be. The composition of the present invention has excellent antibacterial and antifungal properties.
It is safe and has very low irritation,
Infants, infants, children and other patients with skin diseases, patients who are vulnerable to irritation
And so on. Also, the composition of the present invention
Is also useful for patients with atopic dermatitis and contact dermatitis
It can be suitably used. The present invention is broadly applied to Gram-positive bacteria and Gram-
Low-toxic and secondary antibacterial agent with excellent antibacterial activity against bacterium
This is a sterilization method using a composition having an extremely weak effect. Especially above
The composition can be, for example, Staphylococcus, Streptococcus,
Gram-positive terrier bacteria, Mycobacterium tuberculosis, Clostridium, etc.
Fungi, Neisseria, Escherichia, Citrobacter
Genus, Salmonella, Shigella, Klebsiella, shoe
Gram-negative bacteria such as Domonas, Clostridium,
Peptococcus, Peptostreptococcus, Propi
Anaerobic bacteria such as Onibacterium and Bacteroides,
Zygomycetes including Mucor spp., Aspergillus spp.
Ascomycetes including the genus Nisirium, Cryptococcus,
Including Candida spp., Dermatophytes, Pichirosporum spp.
Very strong antibacterial activity against fungi such as complete fungi
I do. Further, the method of the present invention comprises a penicillin
System, quinolone, aminoglycoside, macrolide
Bacteria resistant to various antibiotics such as
Demonstrates excellent antibacterial activity against floor-separated bacteria. Especially M
RSA and MRSE exhibit a remarkable bactericidal effect. Ma
The method of the present invention also comprises quinolone resistance, aminoglycoside resistance,
Macrolide resistance, tetracycline resistance, etc.
It is also effective for drug-resistant MRSA and MRSE. Further, a zinc compound and hinokitiol or a mixture thereof
In combination with salt, Staphylococcus sp.
Suppresses the observed reversal of hinokitiol or its salts
To increase the bactericidal action of hinokitiol or its salts.
Can be increased. The method of the present invention has high safety,
It is a sterilization method with excellent dischargeability. That is, the method of the present invention
According to this, renal excretion is high and bile transfer is also good. Accordingly, the method of the present invention
Cloth, chemical rag, paper towel, towel, carpet
G, floor, tableware, general clothing, general utensils (eg, home
Utensils, glasses, etc.), washing of medical clothing, dishwasher,
Sterilization of drain pipes and other medical equipment (eg gauze, optical
Cleaning or removal of beverage storage containers, animal tools, etc.
It can be suitably applied to bacteria and the like. EXAMPLES The present invention will be described below with reference to Production Examples and Test Examples.
I will make it even clearer. In the following, simply "%" means
It means "% by weight". Production Example 1 (Zinc flower ointment) Hinokitiol 0.5 g Lardum 300.0 g Salamander beeswax 60.0 g Zinc oxide 100.0 g White petrolatum Appropriate amount Total 1000.0 g (1) Hinokitiol is weighed, and Add some of the lard
Then, the mixture was heated to about 40 ° C. and uniformly stirred and melted. (2) Remaining
Dissolve lard, white beeswax and white petrolatum in a water bath
After unraveling, the mixture was stirred to form a mixture at 80 ° C. (3)
Weigh zinc oxide in a mortar and mix as prepared in (2) above.
Stir evenly while adding little by little to about 40 ° C.
Then, the mixture was cooled with stirring. (4) Then, adjust in (1) above.
After adding the prepared mixture at about 40 ° C.,
The mixture was stirred thoroughly to obtain the desired zinc white ointment. Production Example 2 (Zinc flower ointment) Hinokitiol 0.1 g Olive oil 100.0 g Zinc oxide 100.0 g Pharmacopoeia simple ointment qs 1000.0 g (1) Hinokitiol was weighed, and olive oil was added to it.
The mixture was heated to about 40 ° C. and uniformly stirred and melted.
(2) Dissolve the remaining olive oil and ointment ointment on a water bath
After stirring, a mixture was formed at 80 ° C. (3) Milk
The zinc oxide is weighed in a pot, and the mixture prepared in (2) above is weighed.
Stir evenly while adding little by little to reach about 40 ° C
The mixture was cooled under stirring. (4) Then, prepared in (1) above
After adding the mixture at about 40 ° C,
After stirring, an intended zinc white ointment was obtained. Production Example 3 (Water-absorbing zinc white ointment) Lipophilic glyceryl monostearate 50.0 g Zinc oxide 50.0 g White petrolatum Appropriate amount Hinokitiol sodium salt 0.05 g Glycerin 30.0 g Purified water 50.0 g Total 1000. 0g (1) Hinokitiol sodium salt, glycerin and spirit
Water was heated to about 60 ° C. and uniformly stirred and melted. (2) Parent
Glycerin monostearate and white petrolatum in water
After dissolving in the bath, stir to form a mixture at 60 ° C.
Was. (3) The mixture prepared in the above (2) is added to the above (1)
Stir evenly while adding the mixture prepared in step by step
Then, the mixture was cooled under stirring until the temperature reached about 40 ° C. (4) In a mortar
The zinc oxide is weighed, and the mixture prepared in (3) above is reduced.
After the addition, stir well until it hardens,
Hua ointment was obtained. Production Example 4 (Vanishing cream) Stearic acid 10.0% Paraffin wax (135F) 2.0% Whale wax 2.0% Cetyl alcohol 2.0% Cetyl isooctanoate 5.0% Polyoxyethylene sorbitan monolaurate (20EO) 3.0% zinc acetate 0.015% sodium hydroxide 0.15% concentrated glycerin 5.0% hinokitiol 0.02% perfume qs purified water residue total 100.0% (1) stearic acid, Paraffin wax (135
F), whale wax, cetyl alcohol, cetyl isooctanoate
And monolaurate polyoxyethylene sorbitan
(20EO) is heated to 80-85 ° C and melted uniformly
Was. (2) Zinc acetate, sodium hydroxide, concentrated glycerin
And purified water was heated to 80 to 85 ° C. and uniformly dissolved.
(3) The mixture prepared in (1) above at 80 ° C.
Add the mixture prepared in (2) little by little, and add milk
After that, the mixture was cooled to 45 ° C. with stirring. (4) at 45 ° C
Hinokitiol and fragrance were added to the mixture prepared in (3) above.
After adding the ingredients, stir evenly, then cool to room temperature with stirring.
Thus, the desired burnishing cream was obtained. The burnishing
The ream was a stable emulsion. Production Example 5 (Cleansing Cream) Salami beeswax 3.0% Liquid paraffin 30.0% Cetyl alcohol 2.0% Cetyl isooctanoate 10.0% Triethanolamine 0.2% Propylene glycol 5.0% Zinc acetate 0.1% Antioxidant appropriate amount Hinokitiol 0.05% Fragrance appropriate amount Purified water residue Total 100.0% Each of the above components was added according to Example 4 and emulsified.
After all, a stable emulsion was obtained. Production Example 6 (Milk Lotion) Stearic acid 3.0% Whale wax 3.0% Lipophilic glyceryl monostearate 2.0% Salami beeswax 2.0% Saturated fatty acid (C ₈ ~ C ₁₂ ) Triglyceride 10.0% L-arginine 1.0% Sorbitol 3.0% Zinc pyrithione 0.02% Hinokitiol 0.02% Fragrance 0.1% Purified water Residue total 100.0% Emulsified by adding according to
After all, a stable emulsion was obtained. Production Example 7 (Lotion) Ethyl alcohol 10.0% Polyoxyethylene lauryl ether (9EO) 2.0% Photosensitizer 201 0.001% Perfume Appropriate amount Concentrated glycerin 5.0% 1,3-butylene Glycol 3.0% Hinokitiol zinc 0.05% Hinokitiol 0.05% Color appropriate amount Purified water Residue total 100.0% (1) Polyoxyethylene lauryl in ethyl alcohol
Ether (9EO), Photosensitizer 201, Hinokitiol
Add zinc, hinokitiol and fragrance and mix evenly
Was. (2) Concentrated glycerin and 1,3-butylene in purified water
Glycol was added and dissolved uniformly. (3) at 60 ° C
The mixture prepared in (2) above is added to the mixture prepared in (1) above.
The mixture, mix evenly, color with pigment, lotion
Got. Production Example 8 (Zinc flower ointment) Tallow 20.95% Salami beeswax 7.0% Lipophilic glyceryl monostearate 2.0% White petrolatum 60.0% Zinc oxide 10.0% Hinokitiol 0.05% Total 100.0% (1) Weigh hinokitiol and add part of lard to this
Then, the mixture was heated to about 40 ° C. and uniformly stirred and melted. (2) Remaining
Lard, lipophilic glyceryl monostearate, salamisimi
Dissolve the wax and petrolatum in a water bath and stir.
To form a mixture at 80 ° C. (3) Zinc oxide in mortar
Weigh and add the mixture prepared in (2) above little by little
Stir evenly and cool under stirring until it reaches about 40 ° C
did. (4) Next, the mixture prepared in the above (1) is
After adding at about 40 ° C, stir well until hardened,
A zinc white ointment was obtained. Production Example 9 (Disinfectant for pump) Hinokitiol 0.05 g Zinc chloride 0.04 g 99.5% ethanol 70.0 g Total amount with purified water 100.0 g Production Example 10 (pet shampoo) sodium lauroylmethylalanine ( 30%) 40.0 g Coconut oil fatty acid amidopropyl dimethylaminoacetic acid betaine 10.0 g Hinokitiol 0.1 g 99.5% ethanol 3.0 g Zinc chloride 0.08 g pH adjuster Appropriate amount Purified water total amount 100.0 g Production example 11 (Soap bar) Soap base 30.0 g Hardened coconut oil fatty acid sodium glyceryl sulfate 50.0 g Glyceryl monostearate 5.0 g Cetyl alcohol 5.0 g Titanium dioxide 0.5 g Zinc oxide 0.5 g Hinokitiol 0.05 g Fragrance, antioxidant Agent and sequestering agent Production Example 12 (Instrument cleaning agent) Coconut fatty acid sodium methylalanine (25%) 15.0 g Coconut fatty acid amidopropyldimethylaminoacetic acid betaine 5.0 g Hinokitiol / triethanolamine salt 0.01 g Hinokitiol / L-arginic acid 0 0.03 g Zinc gluconate 0.001 g pH adjuster Appropriate amount Total amount with purified water 100.0 g Production Example 13 (detergent for liquid Landry) Polyoxyethylene lauryl ether 35.0 g Alkylbenzenesulfonic acid triethanolamine salt 15.0 g Hinokitiol. 2-Amino-2-methyl-1,3-propanediol salt 0.5 g Zinc chloride 0.4 g Total amount with purified water 100.0 g Production Example 14 (liquid Landry detergent) Alkylbenzenesulfonic acid triethanolamine salt 19.0 g Polio Ciethylene dodecyl ether 7.0 g Sodium meta-xylene sulfonate 6.0 g Triethanolamine citrate 8.0 g Carboxymethyl cellulose 0.5 g Hinokitiol 2-amino-2-methyl-1,3-propanediol salt 1.0 g Citric acid Zinc 0.4 g Fluorescent whitening agent and fragrance qs. 0.0 g hinokitiol zinc 0.5 g hinokitiol sodium salt 0.5 g Fluorescent whitening agent and perfume qs 100.0 g with purified water Production Example 16 (bathroom cleaner) Polyoxyethylene alkyl (C ₁₂ ) Ether 10.0 g Citric acid 5.0 g Polypropylene glycol 5.0 g 99.5% ethanol 3.0 g Hinokitiol 0.05 g Zinc acetate 0.05 g pH adjuster Appropriate amount Total amount with purified water 100.0 g Production example 17 (toilet) Cleaning agent) Hydrochloric acid 9.5 g Sodium chloride 7.0 g Polyoxyethylene alkyl (C ₁₂ ) Ether 2.0 g Thickener 2.5 g Hinokitiol 0.03 g Zinc chloride 0.5 g pH adjuster Appropriate amount Total amount with purified water 100.0 g Production Example 18 (wiping agent, stock solution for aerosol) Liquid paraffin 0.3 g sucrose Fatty acid ester 2.0 g 1,3-butylene glycol 3.0 g Hinokitiol 0.02 g 99.5% ethanol 5.0 g Zinc chloride 0.01 g Total amount in purified water 100.0 g Reference example Test bacteria used in the following test examples Among them, MRSA-1,
MRSA-2 and MRSA-3 are both methicillin
It is resistant Staphylococcus aureus and is resistant to methicillin and
Resistance, aminoglycoside resistance, macrolide resistance and
It has tracyclin resistance. Also MRSE
-1 is methicillin-resistant Staphylococcus epidermidis. MRSA-1, MRSA-2 and MRSA
-3, hinokitiol, methicillin sodium
(Penicillin), ofloxacin (quinolone agent), sulfuric acid
Acid gentamicin (aminoglycoside), erythromycin
(Macrolide) or minocycline hydrochloride (tetracycline)
Clin) in the presence of the minimum inhibitory concentration (M
IC). Table 1 shows the results. [Table 1] For MRSE-1, methicillin sodium
Growth inhibition on a medium in the presence of serum (penicillin)
The static concentration (MIC) was examined. Table 2 shows the results. [Table 2] From the results in Tables 1 and 2, the MIC value was
More than 12.5 strains were defined as resistant strains. For example, MRSA-
In the case of 1, ofloxacin 12.5 μg / ml (→ quino
Gentamicin sulfate> 100 μg / ml
(→ aminoglycoside resistance), erythromycin> 100μ
g / ml (→ macrolide resistant), minocycline hydrochloride
25 μg / ml (tetracycline resistance)
Ron resistance, aminoglycoside resistance, macrolide resistance, tet
Can be judged as MRSA with lacyclin resistance
You. Test Example 1 (Antimicrobial Test) Hinokitiol SP (Takasago International Corporation)
Lot. 112108) and zinc oxide (Wako
Lot. 71620) was used. Also
Staphylococcus epid
ermidis KPU1 (Staphylococcus epidermidis)
Was. Preculture on SCD slant medium (18-20 hours)
Cells at 37 ° C.) in an SCD medium
And dilute this to 10 ⁶ -10 ⁷ Adjust to pieces / ml,
Adapted for several tens minutes. Bring this bacterial solution to the specified concentration
After the addition to the previously prepared drug, shake culture is performed.
The number of viable cells was measured over time (diluent: SCDLP culture).
Ground or sterile physiological saline, medium: SCDLP agar medium, medium
Cultivation temperature: 37 ° C, culture time: 24-48 hours). The working concentration and preparation method of the drug are as follows.
is there. That is, the control is performed by adding the bacterial solution to 1 ml of sterile distilled water.
9 ml was added. Hinokitiol (0.0
2%) is an alcohol solution containing 5% hinokitiol.
Dilute the solution with sterile distilled water and add hinokitiol 0.2% solution.
This was prepared by adding 9 ml of bacterial solution to 1 ml of this solution.
You. Hinokitiol (0.04%) is hinokitiol
Is diluted with sterile distilled water containing 5%
Prepare a 0.4% solution of hinokitiol and add 1 ml of this
9 ml of the liquid was added. Zinc oxide (0.1%)
Add 10 ml of bacterial solution to 0.01 g of zinc oxide (ZnO)
It has been added. Hinokitiol (0.04%) + acid
Zinc oxide (0.1%) is added to 0.01 g of zinc oxide
After adding 1 ml of all 0.4% solution, add 9 ml of bacterial solution
It is a thing. Zinc acetate (0.4%) is converted to zinc acetate (Z
n (CH _Three COO) _Two ・ 2H _Two O) Bacterial solution 1 in 0.04 g
0 ml was added. Hinokitiol (0.0
2%) + zinc acetate (0.4%) is 0.04 g of zinc acetate
After adding 1 ml of a 0.2% hinokitiol solution to
ml. The number of viable bacteria over time was determined, and the results were shown in FIG.
2 and FIG. As is clear from FIG. 1 and FIG.
By using thiol and zinc oxide or zinc acetate together
It can be seen that the antibacterial activity is significantly improved. Test Example 2 (Antibacterial Test) Hinokitiol SP (Takasago International Corporation)
Lot. 209106) and zinc chloride (Hanei)
Lot. M3B1104),
MRSA-1 was used as a test bacterium. Tryptoso
-Pre-cultured in yabouillon medium (18-20 hours, 37 ° C)
Prepared in a heart infusion broth medium
Prepared to the specified concentration in the above test bacterial solution in several growth phases
After the above-mentioned drug is acted on, shaking culture is performed at 37 ° C.
The number of viable cells was measured over time (diluent: SCDLP culture).
Ground, medium: SCDLP agar medium, culture time: 24-48
time). The preparation method of the drug is as follows. That is, cypress
Thiol is an alcohol solution containing 5% hinokitiol
Dilute the solution with sterile distilled water, 10 times and 20 times the working concentration
A solution was prepared. Zinc chloride dissolves in sterile distilled water and acts
Solutions of 10 and 20 times the concentration were prepared. By itself
Add 7.2 ml of bacterial solution to 0.8 ml of the above 10 times solution
However, in the combined action, the bacteria were added to 0.4 ml each of the 20-fold solution.
Add 7.2 ml of liquid and use sterile distilled water for control.
To 0.8 ml, 7.2 ml of the bacterial solution was added. The number of viable cells over time was determined, and the results are shown in FIG.
4 and 5. As is apparent from FIGS.
Antibacterial activity is improved by using all and zinc chloride together.
It can be seen that it is improved or significantly improved. Test Example 3 (Antibacterial test) Hinokitiol and acetate
The effect of the combined use of lead was investigated. Hinokitiol SP and vinegar as test drugs
Zinc acid (Lot. LKR 339, manufactured by Wako Pure Chemical Industries, Ltd.)
5) was used. In addition, as the test bacteria, the following six bacteria
The strain was used. Strain used: Staphylococcus (S.) aureus
209PJC S.P. aureus ATCC 6538 (yellow grapes
S. aureus) epidermidis KPU1 (epidermal grape
Escherichia coli K-12 (colon)
Bacteria) Escherichia coli ATCC 873
9 (E. coli) Bacillus subtilis IAM1213
(Bacillus subtilis) Bacterial solution was pre-cultured in Mueller Hinton medium (culture temperature:
(37 ° C, culture time: 18 to 20 hours).
Dilute with Mineral Hinton medium and add 10 ⁸ Pieces / ml or 1
0 ⁶ Those prepared at a number of cells / ml were used. The working concentration and preparation method of the drug are as follows.
is there. That is, an alcohol containing 5% hinokitiol
Dilute the solution with sterile distilled water, add 0.4% hinokitiol
And dilute the solution two-fold sequentially with sterile distilled water.
2000 μg / ml, 1000 μg / ml, 500
μg / ml, 250 μg / ml, 125 μg / ml, 6
2.5 μg / ml, 31.3 μg / ml, 15.6 μg
/ Ml was prepared. In addition, zinc acetate was used for 3.
The aqueous solution containing 2% is diluted twice with sterile distilled water sequentially,
16000 μg / ml, 8000 μg / ml, 4000
μg / ml, 2000 μg / ml, 1000 μg / m
1, 500 μg / ml, water containing 250 μg / ml
A solution was prepared. When hinokitiol and zinc acetate are used in combination,
In this case, a 20-fold solution of the above two drugs at a working concentration of 0.5 was used for each.
Add 9 ml of medium and 9 ml of medium to Petri dish to prepare plate medium
did. Hinokitiol and zinc acetate were used alone.
When using, use a 10-fold solution of hinokitiol or zinc acetate 1
ml and 9 ml of the medium are added to a Petri dish to prepare a plate medium.
Made. Hinokitiol and / or zinc acetate
Mueller-Hinton plate medium at a concentration of
10 ⁸ Pieces / ml or 10 ⁶ Pieces / ml
After inoculating the prepared various bacterial solutions and culturing at 37 ° C. for 48 hours,
The presence or absence of development was determined. The results are shown in Tables 3 to 8 below.
In the table below, "+" indicates that there is development,
"-" Indicates no growth, and "±"
Indicates that there is development. [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8] As is clear from Tables 3 to 8 above,
Antibacterial activity can be achieved by using both chithiol and zinc acetate.
It can be seen that the properties are significantly improved. Test Example 4 (Antibacterial Test) The same method as in Test Example 3 (however, only the medium was changed.
As a preculture, tryptosome bouillon medium was diluted.
Dried bouillon medium for exfoliation, heart-in for plates
Fusion agar medium was used. ) By hinokichi
The effect of the combination of all and zinc chloride at 24
The time was examined after incubation. Hinokitiol SP and salts as test drugs
Zinc oxide (Lot. TWQ 127, manufactured by Wako Pure Chemical Industries, Ltd.)
7) was used. In addition, four kinds of bacteria shown below were used as test bacteria.
The strain was used. Strain used: Staphylococcus aureus 209
PJC Bacillus subtilis PCI 219 Micrococcus luteus ATCC 9
341 MRSA-1 MRSA-2 The results are shown in Tables 9 to 11 below. [Table 9] [Table 10] [Table 11] Test Example 5 (Antibacterial Test) The same method as in Test Example 3 (however, only the medium was changed.
As a preculture, tryptosome bouillon medium was diluted.
Dried bouillon medium for exfoliation, heart-in for plates
Fusion agar medium was used. ) By hinokichi
The effect of the combination of all and zinc dipicolinate was 3
It was examined after culturing at 7 ° C for 24 hours. As test drugs, hinokitiol SP and
Lead dipicolinate was used. In addition,
The two strains shown were used. Strains used: Staphylococcus epidermidi
s KPU-1 Bacillus subtilis ATCC 66
33 The results are shown in Table 12 below. [Table 12] Test Example 6 (Antibacterial Test) The same method as in Test Example 3 (however, only the medium was changed.
As a preculture, tryptosome bouillon medium was diluted.
Dried bouillon medium for exfoliation, heart-in for plates
Fusion agar medium was used. ) By hinokichi
The effect of the combination of all and zinc oxide was 24 hours at 37 ° C.
The time was examined after incubation. Hinokitiol SP and acid as test drugs
Zinc oxide was used. Also, MRSA-3 was used as the test bacterium.
Used. The results are shown in Table 13 below. [Table 13] Test Example 7 (Antibacterial Test) The same method as in Test Example 3 (however, only the medium was changed.
As a preculture, tryptosome bouillon medium was diluted.
Dried bouillon medium for exfoliation, heart-in for plates
Fusion agar medium was used. ) By hinokichi
All and zinc sulfate (Lot. P, manufactured by Hanui Tesque Co., Ltd.)
TN2474) for 24 hours at 37 ° C
It was examined after culture. As test agents, hinokitiol SP and sulfuric acid
Zinc acid heptahydrate was used. In addition,
The three strains shown were used. Strain used: MRSA-1 MRSA-2 MRSE-1 The results are shown in Tables 14 and 15 below. [Table 14] [Table 15]

[Brief description of the drawings] FIG. 1 is a graph showing the change over time in the number of viable bacteria. FIG. 2 is a graph showing the change over time in the number of viable bacteria. FIG. 3 is a graph showing the change over time in the number of viable bacteria. FIG. 4 is a graph showing the change over time in the number of viable bacteria. FIG. 5 is a graph showing the change over time in the number of viable bacteria.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁷ Identification code FI A61K 31/12 A61K 31/12 33/30 33/30 A61P 17/00 A61P 17/00 101 101 (58) Fields surveyed (Int. .Cl. ⁷ , DB name) A61K 31/315 A61K 7/00 A61K 31/12 A61K 33/30 A61P 17/00 CA (STN) REGISTRY (STN) MEDLINE (STN) BIOSIS (STN) EMBASE (STN)

Claims (1)

(57) [Claim 1] A composition for washing or disinfecting MRSA, comprising a zinc compound and hinokitiol or a salt thereof .
If the object to be cleaned or disinfected is wet tissue,
Width, paper towel, towel, carpet, floor
ー, tableware, general clothing, general utensils, medical clothing, dishwashing
For purifiers, drains, medical equipment, beverage storage containers or animals
A cleaning or disinfecting composition which is a tool .