CN101011058A - Disinfectant and/or bactericidal aqueous compositions - Google Patents
Disinfectant and/or bactericidal aqueous compositions Download PDFInfo
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- CN101011058A CN101011058A CN 200710087510 CN200710087510A CN101011058A CN 101011058 A CN101011058 A CN 101011058A CN 200710087510 CN200710087510 CN 200710087510 CN 200710087510 A CN200710087510 A CN 200710087510A CN 101011058 A CN101011058 A CN 101011058A
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Abstract
An aqueous composition for disinfection and/or sterilization, characterized by containing an olanexidine acid addition salt and one or more polyoxyethylene type nonionic surfactants selected from the group consisting of higher alkyl esters of polyoxyethylene and polyoxyethylene alkylphenyl ethers; an aqueous composition for disinfection and/or sterilization, characterized by having an olanexidine acid addition salt concentration of 0.05 to 0.5 w/v% and an alcohol concentration of 20 to 80 w/v% and containing no surfactants; and an aqueous composition for disinfection and/or sterilization, characterized by containing an olanexidine acid addition salt and an ester type nonionic surfactant and/or a cyclic oligosaccharide.
Description
The application is to be the application number on May 25th, 2004 (the PCT application number: PCT/JP2004/007436), denomination of invention divides an application for " sterilization and/or bactericidal aqueous compositions " that is 200480014613.5 applying date.
Technical field
The present invention relates to contain the sterilization and/or the bactericidal aqueous compositions of Olanexidine (olanexidine) acid-addition salts.
Background technology
Nowadays, people and thing are often travelled around the world, and the pathogenic microorganisms that only limits to specific region or country before therefore having increased is brought to each local risk of the world.In addition, in the modern life, people more and more have health consciousness, and begin to build hygienic conditions.But, in contrast, it is said that people's immunologic function descends.
In this case, avoid the infringement of pathogenic microorganisms, just need exploitation to use safe ready and the stronger disinfectant/bactericide of effect in order to protect humans and animals.
[1-(3 for Olanexidine, 4-dichloro-benzenes methyl)-5-octyl group biguanides] and salt be to have developed the compound that satisfies above-mentioned needs with sterilization/bactericidal action, and have than hitherto known single biguanides (monobiguanide) derivative (referring to Japan Patent No.2662343, claim 1, paragraph 0018,0019,0067 etc.) broader antimicrobial spectrum.In Japan Patent No.2662343, propose when single Biguanide derivative or its salt are used as disinfectant, by the dissolving of its ormal weight, disperse or be suspended in the medium such as water or organic solvent, thereby obtain liquid preparation for external application, for example eye drops, nasal drop, gargle, cleaning agent or washing agent.
Olanexidine is an alkali compounds, therefore forms acid-addition salts.Yet for example, the solvability of OPB 2045 in water is very low, is 0.02W/V% in the time of 0 ℃, and under this concentration, and bactericidal activity is subject to the influence of various factors such as pH, serum, soap, temperature etc.Therefore, have tight demand for not being subject to these factor affecting and containing with the Olanexidine of high concentration dissolving or the aqueous formulation of its salt.
Summary of the invention
As mentioned above, Olanexidine and salt thereof can be used as disinfectant and/or bactericide, but can think, by the following main points of further improvement, will improve its practicality.
That is to say, because disinfectant and/or bactericide extensively use as liquid preparation, therefore can be prepared into high as far as possible concentration as the preparation of main agents if contain Olanexidine or its salt, so this bactericidal effect and easy to use aspect will be favourable.This high concentrate formulation can be used for the occasion of the strong bactericidal action of needs, perhaps can as in use the dilution allotment solution, can reduce volumes of formulation in this case, from the dispensing and the storage angle this be favourable.
Need suitable dissolution aids to improve the concentration of Olanexidine, but for the preparation that contains dissolution aids, must stablize the high bactericidal action that keeps Olanexidine, must suppress skin irritation as much as possible, and described preparation must be easy to use.
Yet, up to the present, also there is not the high concentrate formulation of Olanexidine or its salt known, for this preparation, Olanexidine is dissolved in the medium with high concentration, keep high bactericidal activity, and skin irritation is little.Therefore the high concentrate formulation that the purpose of this invention is to provide this Olanexidine or its salt.
To achieve these goals, the inventor makes the dissolution aids of Olanexidine acid-addition salts dissolving carry out many researchs to being used to, found that, above-mentioned purpose can be by in the presence of at least a polyoxyethylene groups non-ionic surface active agent that is selected from polyoxyethylene senior alkyl ether and polyoxyethylene alkyl phenyl ether, the Olanexidine acid-addition salts is dissolved in the aqueous solvent and realizes.
Based on these discoveries, the inventor makes further research, and has realized sterilization of the present invention and/or bactericidal aqueous compositions (hereinafter being called " invention I composition ").
That is to say that invention I composition is sterilization and/or the bactericidal aqueous compositions that contains the Olanexidine acid-addition salts and be selected from least a polyoxyethylene groups non-ionic surface active agent of polyoxyethylene senior alkyl ether and polyoxyethylene alkyl phenyl ether.
The example of polyoxyethylene senior alkyl ether is the represented compound of formula (1):
R
1-O-(CH
2CH
2O)
m-H (1)
R wherein
1Expression has the alkyl of 7-20 carbon atom, and m represents the integer of 9-12.
The example of polyoxyethylene alkyl phenyl ether is the represented compound of formula (2):
R wherein
2Expression has the alkyl of 7-20 carbon atom, and n represents the integer of 9-12.
Preferred invention I composition is that to contain Olanexidine acid-addition salts and the concentration that concentration is 0.05-5W/V% be the waterborne compositions of the polyoxyethylene groups non-ionic surface active agent of 0.1-10W/V%.
Invention I composition comprises the water as solvent, also can comprise alcohol, as long as it can not have a negative impact to effect of the present invention.When using alcohol, the concentration of alcohol is 30-80W/V% in the composition, preferred 60-80W/V%.The example of alcohol comprises ethanol, isopropyl alcohol, denatured alcohol etc.Especially preferred alcohol.
In addition, the inventor also finds in the ethanol water of appointment, even there is not surfactant, also can dissolve a certain amount of Olanexidine acid-addition salts, and sterilization/bactericidal effect is improved.
Based on these discoveries, the inventor makes further research, and has realized sterilization of the present invention and/or bactericidal aqueous compositions (hereinafter being called " invention II composition ").
That is to say that invention II composition is that to contain Olanexidine acid-addition salts and the concentration that concentration is 0.05-0.5W/V% be the waterborne compositions of the alcohol of 20-80W/V%, and does not contain any surfactant.Determining alcohol in the invention II composition is preferably 30-60W/V%.The example of described alcohol comprises ethanol, isopropyl alcohol, denatured alcohol etc., especially preferred alcohol.
Usually, it is the alcohol of 20-80W/V% that invention II composition contains Olanexidine acid-addition salts and the concentration that concentration is 0.05-0.5W/V%, and does not contain any surfactant.
In addition, the inventor finds under the situation of above-mentioned purpose can be by being selected from ester group non-ionic surface active agent and cyclic oligosaccharide in existence at least a component, makes the Olanexidine acid-addition salts soluble in water and realize.
Based on these discoveries, the inventor makes further research, and has realized sterilization of the present invention and/or bactericidal aqueous compositions (hereinafter being called " invention III composition ").
That is to say that invention III relates to following sterilization and/or bactericidal aqueous compositions etc.
1) contains Olanexidine acid-addition salts and the sterilization and/or the bactericidal aqueous compositions that are selected from least a component of ester group non-ionic surface active agent and cyclic oligosaccharide.
2) according to above-mentioned 1) sterilization and/or bactericidal aqueous compositions, wherein the ester group non-ionic surface active agent is to be selected from (i) polyoxyethylene sorbitan fatty acid esters, (ii) polyglyceryl fatty acid ester, (iii) the polyoxyethylene fatty acid glyceride and the (iv) at least a component of Glucam E-10 fatty acid ester.
3) according to above-mentioned 2) sterilization and/or bactericidal aqueous compositions, wherein polyoxyethylene sorbitan fatty acid esters is the compound by general formula (3) expression:
R wherein
11Expression has the alkyl of 10-20 carbon atom, and h, j and k are respectively the integer of 5-25.
4) according to above-mentioned 2) sterilization and/or bactericidal aqueous compositions, wherein polyglyceryl fatty acid ester is by general formula
(4) Biao Shi compound:
R wherein
21-R
25One of expression have the alkanoyl of 10-20 carbon atom, other (p+3) individual expression hydrogen atom, p is the integer of 2-12.
5) according to above-mentioned 2) sterilization and/or bactericidal aqueous compositions, wherein the polyoxyethylene fatty acid glyceride is the compound by general formula (5) expression:
R wherein
31Expression has the alkyl of 6-16 carbon atom, and q is the integer of 4-30.
6) according to above-mentioned 2) sterilization and/or bactericidal aqueous compositions, wherein the Glucam E-10 fatty acid ester is the compound by general formula (6) expression:
R wherein
41Expression has the alkyl of 15-20 carbon atom, and the summation of x and y is the integer of 20-160.
7) according to above-mentioned 1) sterilization and/or bactericidal aqueous compositions, wherein cyclic oligosaccharide is a cyclodextrin.
8) according to above-mentioned 1) sterilization and/or bactericidal aqueous compositions, wherein the concentration of Olanexidine acid-addition salts is 0.05-2.5W/V%, the concentration of ester group non-ionic surface active agent is 0.1-10W/V%.
9) according to above-mentioned 1) sterilization and/or bactericidal aqueous compositions, wherein the concentration of Olanexidine acid-addition salts is 0.1-2.5W/V%, the concentration of ester group non-ionic surface active agent is 0.1-10W/V%.
10) according to above-mentioned 1) sterilization and/or bactericidal aqueous compositions, wherein the concentration of Olanexidine acid-addition salts is 0.05-1W/V%, the concentration of cyclic oligosaccharide is 0.1-10W/V%.
11) according to above-mentioned 1) sterilization and/or bactericidal aqueous compositions, wherein the concentration of Olanexidine acid-addition salts is 0.1-1W/V%, the concentration of cyclic oligosaccharide is 0.1-10W/V%.
12) according to above-mentioned 1) sterilization and/or bactericidal aqueous compositions, also contain alcohol.
13) according to above-mentioned 12) sterilization and/or bactericidal aqueous compositions, wherein in the composition alcohol concentration be 20-80W/V%.
14) give object sterilization or disinfectant method, comprise make described object and effective dose according to above-mentioned 1) sterilization and/or bactericidal aqueous compositions contact.
15) according to above-mentioned 1) sterilization and/or the bactericidal aqueous compositions purposes that is used for sterilization or sterilization.
In specification and claims, except as otherwise noted, the concentration of every kind of composition is expressed as weight per volume percentage " % (W/V) " in sterilization and/or the bactericidal aqueous compositions, that is: the weight of every kind of composition (g)/100mL sterilization and/or bactericidal aqueous compositions.Unless indicate especially, concentration " % (W/V) " all records at 0 ℃.
In specification and claims, " waterborne compositions " is meant the composition that contains water.For example, according to above-mentioned 8) waterborne compositions comprise the ester group non-ionic surface active agent that water as solvent, Olanexidine acid-addition salts that concentration is 0.05-2.5W/V% and concentration are 0.1-10W/V%.
Detailed Description Of The Invention
To describe the present invention in detail below.
The Olanexidine acid-addition salts
" Olanexidine acid-addition salts " in sterilization of the present invention and/or the bactericidal aqueous compositions is meant the salt of Olanexidine and acid (organic acid or inorganic acid).
Be not particularly limited for the acid that forms salt.Organic acid example such as formic acid, acetate, lactic acid, butyric acid, isobutyric acid, alpha-mercapto propionic acid, trifluoroacetic acid, malic acid, fumaric acid, succinic acid, succinic monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, gluconic acid, saccharic acid, ascorbic acid, penicillin, benzoic acid, phthalic acid, salicylic acid, ortho-aminobenzoic acid, benzene sulfonic acid, p-methyl benzenesulfonic acid or methanesulfonic acid, inorganic acid example hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid or carbonic acid.And, be not particularly limited for Olanexidine that forms acid-addition salts and the ratio between the acid, except 1: 1, can also use to have multiple other ratios as 1: 2 salt.
Utilize common salt formation method, as directly acid is mixed with Olanexidine, one or both in dissolving acid and the Olanexidine are in the same place solvent then or are put into acid and Olanexidine in solvent such as the water and dissolve and mix in solvent such as water in advance, prepare acid-addition salts.
Should be noted that the Olanexidine acid-addition salts of indication herein can be used for hereinafter described inventing arbitrary composition of I-III.In every kind of composition of invention I-III, the Olanexidine acid-addition salts is dissolved in the solvent that contains water, and wherein said solvent can contain alcohol as required.In this solution, Olanexidine and acid can form salt, and perhaps the two can exist by free form, and perhaps the gluconate of Olanexidine can coexist with free Olanexidine and free gluconic acid.
Invention I composition
Invention I composition is sterilization and/or the bactericidal aqueous compositions that contains the Olanexidine acid-addition salts and be selected from least a polyoxyethylene groups non-ionic surface active agent of polyoxyethylene senior alkyl ether and polyoxyethylene alkyl phenyl ether.
The concentration of Olanexidine acid-addition salts is preferably 0.05-5W/V% in the composition in the invention I composition.In this concentration range, described composition has high sterilization/bactericidal effect and viscosity easy to use.The concentration of Olanexidine acid-addition salts is preferably 0.05-3.5W/V%, more preferably 0.05-2W/V%.
In invention I composition, the polyoxyethylene groups non-ionic surface active agent is selected from polyoxyethylene senior alkyl ether and polyoxyethylene alkyl phenyl ether.
The preferred embodiment of above-mentioned polyoxyethylene senior alkyl ether is the represented surfactant of aforementioned formula (1), wherein R
1Represented alkyl has 7-20 carbon atom, and preferred 9-14 carbon atom comprises nonyl, decyl, undecyl, dodecyl, tridecyl and myristyl.And, can also use the mixture of multiple polyoxyethylene senior alkyl ether with these alkyl.In formula (1), m is the degree of polymerization of oxygen ethylene unit (OE), and is the integer of 9-12.
The instantiation of this surfactant comprises that POE (9) lauryl ether is (for example by Nikko ChemicalsCo., Ltd. " BL-9EX " of Zhi Zaoing), POE (10) lauryl ether is (for example by Sanyo Chemical Industries, " the Emulmin NL-100 " of Zhi Zaoing) and POE (12) alkyl ether (for example by Sanyo ChemicalIndustries, " the Sannonic SS-120 " that Ltd. makes) Ltd..Herein, the numeral OE degree of polymerization in the bracket after " POE ", i.e. m in the formula (1).
The preferred embodiment of polyoxyethylene alkyl phenyl ether is the represented surfactant of aforementioned formula (2), wherein R
2Represented alkyl has 7-20 carbon atom, preferred 9-14 carbon atom, and instantiation is and above-mentioned R
1The group that represented alkyl is identical.In formula (2), n is the degree of polymerization of oxygen ethylene unit (OE), and is the integer of 9-12.
The instantiation of this surfactant is POE (10) nonylplenyl ether and POE (10) octyl phenyl ether.Herein, the numeral OE degree of polymerization in the bracket after " POE ", i.e. n in the formula (2).
Invention I composition comprises this polyoxyethylene groups non-ionic surface active agent in aqueous solvent, and therefore can easily make the Olanexidine acid-addition salts and be dissolved in wherein liquid preparation with high concentration.In addition, invention I composition is the preparation that can suppress skin irritation and have the good feel of good lubrication can obtain to use the time.
The concentration of polyoxyethylene groups non-ionic surface active agent is preferably 0.1-10W/V% in the composition, especially 0.15-6.5W/V% in the invention I composition.In this surfactant concentration ranges, the sterilization/bactericidal effect of Olanexidine acid-addition salts can be stablized maintenance.
Be made for liquid preparation in order to invent the I composition, need under the situation that has the polyoxyethylene groups non-ionic surface active agent, dissolve the solvent of Olanexidine acid-addition salts.Described solvent is preferably water, perhaps the mixture of water and alcohol (for example ethanol, isopropyl alcohol, denatured alcohol etc.).Preferred solvent is the aqueous solution of the aqueous solution, the especially ethanol of alcohol.In this case, the favourable scope that is present in the concentration of alcohol in the composition is 30-80W/V%, preferred 60-80W/V%.By concentration of ethanol is in this scope, the liquid preparation that contains said components can uniform preparation, and can use easily, and this is because it plays the effect of sterilization/sterilization rapidly and exsiccation fast after use in use.
Therefore, invent normally waterborne compositions of I composition.Described waterborne compositions is the aqueous solution of Olanexidine acid-addition salts and polyoxyethylene groups non-ionic surface active agent, and wherein the concentration of Olanexidine acid-addition salts is 0.05-5W/V%, and the concentration of polyoxyethylene groups non-ionic surface active agent is 0.1-10W/V%.
Scheme as an alternative, invention I composition can be the waterborne compositions that contains alcohol.Except the mixture that makes water and alcohol (especially ethanol) replaces water as the solvent, the described waterborne compositions that contains alcohol is the composition identical with above-mentioned waterborne compositions.Usually, the described waterborne compositions that contains alcohol is the aqueous solution of Olanexidine acid-addition salts, polyoxyethylene groups non-ionic surface active agent and alcohol (especially ethanol), wherein the concentration of Olanexidine acid-addition salts is 0.05-5W/V%, the concentration of polyoxyethylene groups non-ionic surface active agent is 0.1-10W/V%, and the concentration of alcohol (especially ethanol) is 30-80W/V%, preferred 60-80W/V%.
Except said components, if desired, various other components also can be included in the invention I composition, with the further product quality of improving.
For example, from improving the angle of skin care ability and moisture-retaining capacity, preferably comprise one or more fatty acid triglycerides and hydroxypropyl methylcellulose as required.By comprising these components, the effect that suppresses skin irritation is improved, and especially contains under the situation of solvent of ethanol in use.
As for above-mentioned one or more fatty acid triglycerides, any fatty acid triglyceride that is usually used in medicine/disinfectant field can use and be not particularly limited.Usually, preferably be liquid fatty acid triglyceride under atmospheric pressure and about 20 ℃ normal temperature; Example is the triglycerides of fatty acid such as isooctyl acid, sad, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid plus linolenic acid, can use a kind of in these fatty acid triglycerides separately, perhaps can be used in combination wherein two or more.In addition, can use with vegetable oil such as olive oil or rapeseed oil triglycerides as its raw material.
In above-mentioned fatty acid triglyceride, especially can preferably glycerine three tricaprylates, because it has high safety and sensation is better in use.
During use, the preferred concentration of described one or more fatty acid triglycerides in composition is that 0.01-10W/V%, especially concentration are 0.3-3W/V%.If described concentration is in this scope, the effect of moistening effect and inhibition skin irritation, pachylosis etc. will fully show so, and hardly can residual tack at skin surface.
Under the situation of using hydroxypropyl methylcellulose, preferably its concentration in composition is 0.001-1.0W/V%, especially 0.005-0.5W/V%.
In addition, one or more can be joined traditionally component in disinfectant/bactericide and join in the invention I composition, only otherwise the purpose of infringement invention I composition.Described in the open No.11-199476 of Japanese unexamined patent, the example is blood circulation accelerant such as propylene carbonate, N-N-methyl-2-2-pyrrolidone N-(Japanese drug excipient), propane diols, polysorbate80 (Japanese Pharmacopoeia) and tocopherol acetate; Organized renewing agent such as allantoin; Freshener such as peppermint oil and 1-menthol; Oily components such as atoleine, polymethyl siloxane, PSI and saualane; Polyalcohol such as glycerine, 1,3-butanediol and sorbitol; The pH regulator agent; Or the like.
The pH of invention I composition is preferably 4-8,5-6 more preferably, and its form be the allotment solution that dilutes in use.If pH is adjusted to this scope, so described composition will have good stable, and the sensation when using is also good.
For example, invention I preparation of compositions can be by adding entry and mix and dissolve in Olanexidine acid-addition salts (for example OPB 2045) and polyoxyethylene groups non-ionic surface active agent, as watery hydrochloric acid etc. mixture is adjusted to the about 4-8 of pH and carries out with sour.This composition can be used for sterilization or sterilization.If desired, when this composition uses as the allotment solution that dilutes in use, can prepare liquid preparation by the described composition of dilutions such as water with prescribed concentration.
Invention II composition
Next, invention II composition is that to contain Olanexidine acid-addition salts and the concentration that concentration is 0.05-0.5W/V% be the waterborne compositions of the alcohol of 20-80W/V%, and does not contain any surfactant in said composition.The concentration of alcohol is preferably 30-60W/V%.The example of alcohol comprises ethanol, isopropyl alcohol, denatured alcohol etc., especially preferred alcohol.
Be different from invention I composition, said composition does not contain surfactant, but can show sterilization/bactericidal action rapidly, and can improve the exsiccation speed after the use.
Usually, invention II composition is that to contain Olanexidine acid-addition salts and the concentration that concentration is 0.05-0.5W/V% be the waterborne compositions of the alcohol of 20-80W/V%, and does not contain any surfactant.
Except said components, if desired, various other components also can be included in the invention II composition, with the further product quality of improving.
For example, from improving the angle of skin care ability and moisture-retaining capacity, preferably comprise one or more fatty acid triglycerides and hydroxypropyl methylcellulose as required.By comprising these components, the effect that suppresses skin irritation is improved, and especially contains under the situation of solvent of ethanol in use.
As for above-mentioned one or more fatty acid triglycerides, any fatty acid triglyceride that is usually used in medicine/disinfectant field can use and be not particularly limited.Usually, preferably be liquid fatty acid triglyceride under atmospheric pressure and about 20 ℃ normal temperature; Example is the triglycerides of fatty acid such as isooctyl acid, sad, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid plus linolenic acid, can use a kind of in these fatty acid triglycerides separately, perhaps can be used in combination wherein two or more.In addition, can use with vegetable oil such as olive oil or rapeseed oil triglycerides as its raw material.
In above-mentioned fatty acid triglyceride, especially can preferably glycerine three tricaprylates, because it has high safety and sensation is better in use.
During use, the preferred concentration of described one or more fatty acid triglycerides in composition is that 0.01-10W/V%, especially concentration are 0.3-3W/V%.If described concentration is in this scope, the effect of moistening effect and inhibition skin irritation, pachylosis etc. will fully show so, and hardly can residual tack at skin surface.
Under the situation of using hydroxypropyl methylcellulose, preferably its concentration in composition is 0.001-1.0W/V%, especially 0.005-0.5W/V%.
In addition, one or more can be joined traditionally component in disinfectant/bactericide and join in the invention II composition, only otherwise the purpose of infringement invention II composition.Described in the open No.11-199476 of Japanese unexamined patent, the example is blood circulation accelerant such as propylene carbonate, N-N-methyl-2-2-pyrrolidone N-(Japanese drug excipient), propane diols, polysorbate80 (Japanese Pharmacopoeia) and tocopherol acetate; Organized renewing agent such as allantoin; Freshener such as peppermint oil and 1-menthol; Oily components such as atoleine, polymethyl siloxane, PSI and saualane; Polyalcohol such as glycerine, 1,3-butanediol and sorbitol; The pH regulator agent; Or the like.
For example, invention II composition can and dissolve by mixing Olanexidine acid-addition salts (for example OPB 2045) in the aqueous solution (for example ethanol water of 50-90%) of alcohol, as watery hydrochloric acid etc. solution is adjusted to the about 4-8 of pH and prepares with sour.This composition can be used for sterilization or sterilization.If desired, when this composition uses as the allotment solution that dilutes in use, can prepare liquid preparation by the described composition of dilutions such as water with prescribed concentration.
Invention III composition
Invention III composition is sterilization and/or the bactericidal aqueous compositions that contains the Olanexidine acid-addition salts and be selected from least a component of ester group non-ionic surface active agent and cyclic oligosaccharide.
Under the situation that exists ester group non-ionic surface active agent and/or cyclic oligosaccharide as the dissolution aids of Olanexidine acid-addition salts, prepare invention III composition by the Olanexidine acid-addition salts that in aqueous solvent, dissolves as main agents.
The ester group non-ionic surface active agent is the surfactant that comprises non-electrolysis molecule, described non-electrolysis molecule is the ester with material of the material of hydrophobic group (fatty acid residue such as nonyl, decyl, undecyl, dodecyl, myristyl etc.) and possess hydrophilic property group (polyoxyethylene group, hydroxyl etc.), it is a nonionic, and can not be dissociated into ion, be to have the surfactant that improves Olanexidine acid-addition salts character of solvability in water.
Usually, can use the ester group non-ionic surface active agent of HLB (hydrophilic-lipophilic balance (HLB)) value as 8-20, preferred 12-16.
Invention III composition preferably comprises the Olanexidine acid-addition salts that at least a component that is selected from ester group non-ionic surface active agent and cyclic oligosaccharide that concentration is 0.1-10W/V% and concentration are 0.05-2.5W/V%.
The example of this ester group non-ionic surface active agent comprises (i) polyoxyethylene sorbitan fatty acid esters, (ii) polyglyceryl fatty acid ester, (iii) polyoxyethylene fatty acid glyceride and (iv) Glucam E-10 fatty acid ester.
As above-mentioned polyoxyethylene sorbitan fatty acid esters, can use the polyoxyethylene sorbitan fatty acid esters of various any types, but represented those of preferred formula (3) wherein:
R wherein
11Expression has the alkyl of 10-20 carbon atom, and h, j and k are respectively the integer of 5-25.
R
11Be preferably straight or branched alkyl, especially be preferably straight or branched alkyl with 10-14 carbon atom with 10-20 carbon atom.In addition, h, j and k can be identical or different, are preferably the integer of 5-25 respectively, especially the integer of 5-20.The summation of h, j and k is the integer of 15-30, especially 15-25.
Instantiation comprises polyoxyethylene (POE) dehydrated sorbitol mono-fatty acid ester, polyoxyethylene (POE) sorbitan monostearate, polyoxyethylene (POE) sorbitan monopalmitate and polyoxyethylene (POE) sorbitan isostearate.The summation (h+j+k) of oxygen ethylene unit (OE) is preferably 15-30 in every kind of compound, 15-25 more preferably, especially 20.
In containing the present composition of polyoxyethylene sorbitan fatty acid esters, the content of polyoxyethylene sorbitan fatty acid esters in composition is preferably 0.1-10W/V%, especially 1.5-3W/V%, the content of Olanexidine acid-addition salts is preferably 0.05-1.5W/V%, especially 0.5-1W/V%.
R
11The example of represented alkyl comprises decyl, undecyl, dodecyl, tridecyl, myristyl, pentadecyl, heptadecyl, octadecyl and nonadecyl.
As above-mentioned polyglyceryl fatty acid ester, can use the polyglyceryl fatty acid ester of various any types, but the represented polyglycereol mono fatty acid ester of preferred formula (4) wherein:
R wherein
21-R
25One of expression have the alkanoyl of 10-20 carbon atom, other (p+3) individual expression hydrogen atom, p is the integer of 2-12.In other words, work as R
21, R
22, R
24And R
25One of when being alkanoyl, other three is hydrogen, each R
23Also be hydrogen, as (p) individual R
23In one when being alkanoyl, (p-1) individual R in addition
23All be hydrogen, R
21, R
22, R
24And R
25Also be hydrogen.
Described R
21-R
25One of be preferably straight or branched alkanoyl with 10-20 carbon atom, more preferably have the straight or branched alkanoyl of 5-16 carbon atom, especially preferably have a straight or branched alkanoyl of 10-14 carbon atom.In addition, p is preferably the integer of 2-12, especially is preferably the integer of 8-10.
Instantiation comprises polyglycereol monolaurate such as DECAGLYCERYL MONOLAURATE; The polyglycereol monoleate is as six glycerin mono-fatty acid esters and SY-Glyster MO 750; And the polyglycereol monostearate is as two glyceryl monostearates.
In containing the present composition of polyglyceryl fatty acid ester, the content of polyglyceryl fatty acid ester in composition is preferably 0.1-10W/V%, especially 3.0-6.0W/V%, and the content of Olanexidine acid-addition salts in composition is preferably 0.05-1.5W/V%, especially 0.5-1W/V%.
R
21-R
25One of the example of represented alkanoyl comprise capryl, hendecane acyl group, dodecane acyl group, tridecane acyl group, tetradecane acyl group, pentadecane acyl group, heptadecane acyl group, octadecanoyl and nonadecane acyl group.
As above-mentioned polyoxyethylene fatty acid glyceride, can use the polyoxyethylene fatty acid glyceride of various any types, but represented those of preferred formula (5) wherein:
R wherein
31Expression has the alkyl of 6-16 carbon atom, and q is the integer of 4-30.
R
31Be preferably straight or branched alkyl, especially be preferably straight or branched alkyl with 8-10 carbon atom with 6-16 carbon atom.Q is preferably the integer of 4-30, especially the integer of 6-15.
Instantiation comprises polyoxyethylene glyceryl cocoate (q=5-10, especially 7), polyoxyethylene glycerol caprylate/decylate (q=5-10, especially 7), polyoxyethylene glyceryl monolaurate (q=5-10, especially 7) and polyoxyethylene glycerine list isostearate (q=10-20, especially 15).
In the present composition that contains the polyoxyethylene fatty acid glyceride, the content of polyoxyethylene fatty acid glyceride in composition is preferably 0.1-10W/V%, especially 2-5W/V%, the Olanexidine acid-addition salts in composition content be preferably 0.05-2.5W/V%, 0.5-1W/V% especially.
R
31The example of represented alkyl comprises hexyl, heptyl, octyl group, nonyl, decyl, undecyl, dodecyl, tridecyl, myristyl, pentadecyl and cetyl.
As above-mentioned Glucam E-10 fatty acid ester, can use the Glucam E-10 fatty acid ester of various any types, but the represented Glucam E-10 di fatty acid ester of preferred formula (6) wherein:
R wherein
41Expression has the alkyl of 15-20 carbon atom, the integer that adds and be 20-160 of x and y.
R
41Be preferably straight or branched alkyl, especially be preferably straight or branched alkyl with 16-18 carbon atom with 15-20 carbon atom.In addition, x and y can be identical or different, are preferably the integer of 5-100 respectively, especially the integer of 10-70.The summation of x and y is preferably the integer of 20-160, especially the integer of 100-140.
Instantiation comprises Glucam E-10 dioleate and Glucam E-10 distearate.
In the present composition that contains the Glucam E-10 fatty acid ester, the content of Glucam E-10 fatty acid ester is preferably 0.1-10W/V%, especially 5-10W/V%, the content of Olanexidine acid-addition salts is preferably 0.05-1.5W/V%, especially 0.5-1W/V% calculates with respect to composition.
As above-mentioned cyclic oligosaccharide, select to have character that improves Olanexidine acid-addition salts solvability in water and the cyclic oligosaccharide that does not damage sterilization/bactericidal action.Wherein can preferably use cyclodextrin.Known three kinds of cyclodextrin, promptly alpha-cyclodextrin, beta-schardinger dextrin-and gamma-cyclodextrin can use above any in the present invention.
In containing the present composition of cyclic oligosaccharide, the content of cyclic oligosaccharide (especially cyclodextrin) is preferably 0.1-10W/V%, 1.5-4W/V% especially, and the content of Olanexidine acid-addition salts is preferably 0.05-1W/V%, especially 0.2-0.5W/V% calculates with respect to composition.
Particularly, when using beta-schardinger dextrin-, the content of beta-schardinger dextrin-in composition is preferably 0.1-1.5W/V%.
Ester group non-ionic surface active agent or cyclic oligosaccharide preferably use in above-mentioned concentration range; If use this concentration range, then can show sufficient sterilization/bactericidal effect.
Solvent as in the invention III composition preferably makes water separately, but also can use the solvent that comprises water and alcohol.The example of alcohol comprises ethanol, isopropyl alcohol, denatured alcohol etc., especially preferred alcohol.In this case, the concentration of alcohol is set at 20-80W/V%, and especially 30-60W/V% calculates with respect to composition.
Except said components, if desired, multiple other components also can be included in the invention III composition, with the further product quality of improving.
For example, from improving the angle of skin care ability and moisture-retaining capacity, preferably comprise one or more fatty acid triglycerides and hydroxypropyl methylcellulose as required.By comprising these components, the effect that suppresses skin irritation is improved, and especially contains under the situation of solvent of ethanol in use.
As for above-mentioned one or more fatty acid triglycerides, any fatty acid triglyceride that is usually used in medicine/disinfectant field can use and be not particularly limited.Usually, preferably be liquid fatty acid triglyceride under atmospheric pressure and about 20 ℃ normal temperature; Example is the triglycerides of fatty acid such as isooctyl acid, sad, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid plus linolenic acid, can use a kind of in these fatty acid triglycerides separately, perhaps can be used in combination wherein two or more.In addition, can use with vegetable oil such as olive oil or rapeseed oil triglycerides as its raw material.
In above-mentioned fatty acid triglyceride, especially can preferably glycerine three tricaprylates, because it has high safety and sensation is better in use.
During use, the preferred concentration of described one or more fatty acid triglycerides in composition is that 0.01-10W/V%, especially concentration are 0.3-3W/V%.If described concentration is in this scope, the effect of moistening effect and inhibition skin irritation, pachylosis etc. will fully show so, and hardly can residual tack at skin surface.
Under the situation of using hydroxypropyl methylcellulose, preferably its concentration in composition is 0.001-1.0W/V%, especially 0.005-0.5W/V%.
In addition, one or more can be joined traditionally component in disinfectant/bactericide and join in the invention III composition, only otherwise can damage the purpose of invention III composition.Described in the open No.11-199476 of Japanese unexamined patent, the example is blood circulation accelerant such as propylene carbonate, N-N-methyl-2-2-pyrrolidone N-(Japanese drug excipient), propane diols, polysorbate80 (Japanese Pharmacopoeia) and tocopherol acetate; Organized renewing agent such as allantoin; Freshener such as peppermint oil and 1-menthol; Oily components such as atoleine, polymethyl siloxane, PSI and saualane; Polyalcohol such as glycerine, 1,3-butanediol and sorbitol; The pH regulator agent; Or the like.
The pH of invention III composition is preferably 4-8,5-6 more preferably, and its form be the allotment solution that dilutes in use.If pH is adjusted to this scope, this liquid preparation will have good stable so, and the sensation when using is also good.
For example, invention III composition can be by to Olanexidine acid-addition salts (for example OPB 2045) be selected from least a component of ester group non-ionic surface active agent and cyclic oligosaccharide and add entry, mix and dissolve, with watery hydrochloric acid etc. mixture is adjusted to the about 4-8 of pH and prepares.This composition can be used for sterilization or sterilization.If desired, when this composition uses as the allotment solution of dilution in use, can prepare liquid preparation by composition as described in diluting as water or alcohol with solvent with prescribed concentration.
The application of invention I-III composition
Sterilization of the invention described above and/or bactericidal aqueous compositions (invention I-III composition) have wide antimicrobial spectrum for multiple microorganism.For example, for Gram-positive bacteria such as staphylococcus, streptococcus, enterococcus and Listeria and Propionibacterium, and Gram-negative bacteria such as colon bacillus, shigella dysenteriae, detection of Salmonella, citric acid bacillus, klebsiella, enterobacteria, Serratieae, mycetozoan, the root fungus that rubs, Yersinia, vibrios, pseudomonad, acinetobacter calcoaceticus, neisser's coccus, haemophilus and Bacteroides, described composition has effective sterilization and disinfective action.
Described composition also has the antiviral activity for tunicary virus such as influenza virus, human immunodeficiency virus, herpes simplex virus and vesicular stomatitis virus, and has antifungal activity for yeast-like fungi such as candidiasis, novel Cryptococcus and saccharomyces cerevisiae.
Sterilization of the present invention and/or bactericidal aqueous compositions are meant to be widely used in kills, reduces, suppresses the reagent of purpose such as various microorganisms as mentioned above.
Composition of the present invention contacts with the object that contains microorganism by the described composition that makes effective dose and shows sterilization or antimicrobial activity.Contact method is not particularly limited, and its instantiation comprises dipping, spraying, does bath (drybath) etc.The example of described object comprises human skin and/or hand, animal skin, Medical Devices, toilet, bathroom, furniture, article etc.
Therefore, composition of the present invention can be used for suitably to sterilizations such as skin/hand, preoperative skin, compromised skin, Medical Devices, operating room, ward, furniture, equipment and other article.
In addition, composition of the present invention can use by it is impregnated in the base fabric.The example of these base fabrics comprises absorbent cotton, gauze, paper, nonwoven, towel, other fabrics etc.Available this base fabric can be that the decomposable or non-water of water is decomposable.
The present composition that comprises high concentration Olanexidine acid-addition salts (OPB 2045 etc.) can be used as stock solution, and can use according to using by water etc. it to be diluted.
The invention effect
For invention I composition, under the situation that has at least a specific polyoxyethylene groups non-ionic surface active agent, the Olanexidine acid-addition salts can high concentration be dissolved in the solvent as main agents.In addition, invention I composition keeps the high-dissolvability of Olanexidine acid-addition salts, and can not reduce its bactericidal activity, and said composition has less skin irritation, and shows quick sterilization effect and quick-drying.Therefore, said composition can be widely used as sterilization and/or sterilization composition.
When having only the Olanexidine acid-addition salts, the solvability in water is very low, and bactericidal activity is subject to the influence of pH, organic substance, soap, temperature etc.But,, can eliminate this influence, and therefore improve practicality according to invention I composition.
For invention II composition, the concentration of Olanexidine acid-addition salts is not too high, but can show sterilization/bactericidal action rapidly, and can improve the exsiccation speed after the use.
For invention III composition, utilize at least a component that is selected from ester group non-ionic surface active agent and cyclic oligosaccharide, the Olanexidine acid-addition salts can high concentration be dissolved in the solvent as main agents.Compare with the composition that only uses the Olanexidine acid-addition salts, therefore the bactericidal activity of invention III composition improves, even and also can show bactericidal action at short notice.
When having only the Olanexidine acid-addition salts, the solvability in water is very low, and bactericidal activity is subject to the influence of pH, organic substance, soap, temperature etc.But,, can eliminate this influence, and therefore improve practicality according to invention III composition.In addition, use invention III composition, skin irritation is suppressed.
Implement best mode of the present invention
The preferred embodiments of the present invention, example of formulations and test implementation example are described below; But the invention is not restricted to these embodiment.
Should be noted that in these embodiments " % " is meant " % (W/V) ", except as otherwise noted.Sterilization and/or sterilization use preparation of compositions are carried out under room temperature (about 25 ℃) among each embodiment.
The composition of invention I and invention II
Embodiment 1
With 0.5g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) mix and be dissolved into ethanol (the Wako Pure Chemical Industries of 74ml 95%, Ltd.) in, use watery hydrochloric acid that pH is adjusted to 6, add entry then, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
Embodiment 2
About 85ml water is joined 0.1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and 0.32g POE (10) nonylplenyl ether (by Nikko Chemicals Co., Ltd. make) in, and mix and dissolve, pH is adjusted to 5, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
Embodiment 3
About 85ml water is joined 0.1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and 0.32g POE (9) lauryl ether (by Nikko Chemicals Co., Ltd. make) in, and mix and dissolve, pH is adjusted to 5, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
Embodiment 4
About 85ml water is joined 0.1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and 0.32g POE (10) lauryl ether (by Sanyo Chemical Industries, Ltd. make) in, and mix and dissolve, pH is adjusted to 5, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
Embodiment 5
Will about 85ml water join 0.1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and 0.41g POE (12) alkyl (C
12-C
14) in the ether (by Sanyo Chemical Industries, Ltd. make), and mix and dissolve, with pH regulator to 6, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain to sterilize and/or bactericidal aqueous compositions.
Even transferring postpone near 0 ℃ temperature, the aqueous solution of gained also remains clear, colorless among the embodiment 1-5, not precipitation.
Comparative examples 1
The ethanol that 74ml is used for sterilizing joins the 20W/V% chlorhexidine gluconate aqueous solution (Sumitomo Pharmaceuticals Company Limited) of 2.5mL, and fully mix and dissolve, use gluconic acid with pH regulator to 6.0, add entry then, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
Comparative examples 2
With water join 2mL the 10W/V% benzalkonium chloride aqueous solution (Nihon Pharmaceutical Co., Ltd.) in, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
Comparative examples 3
Water is joined in the 20W/V% chlorhexidine gluconate aqueous solution (SumitomoPharmaceuticals Company Limited) of 5mL, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
[evaluation method]
＜security test 〉
For resulting every kind of sterilization and/or bactericidal aqueous compositions in the foregoing description and the comparative examples, as followsly carried out the local skin security test with rabbit (male NZW) according to the Draize method.
Hair on the back of every rabbit is cut, and selected almost there is not to be in island skin and hair cycle preclinical rabbit, and six rabbits are divided into one group.The back of every rabbit is divided into four districts, gets with respect to the center to be point-symmetric two districts as intact skin, and two other district is taken as compromised skin, is using formed 2.5cm length the same day with the dual crossing shape cut by using the 18G entry needle.With applied 0.3ml be subjected to the square napped cotton fabric of the 2.5cm of test solution body with the rayon band attached to application position, and fix by covering with ligature.Used 24 hours afterwards, and removed napped cotton fabric.
Check application position, determine the scoring of erythema, incrustation and oedema according to the Draize criterion.According to using back 24 hours and 72 hours the intact skin and the score calculation present situation skin irritation index (P.I.I) of compromised skin, thereby estimate excitant.These the results are shown in the table 1.
Table 1
| Composition | P.I.I |
| Embodiment 1 | 0.7 |
| Embodiment 2 | 0.4 |
| Embodiment 3 | 0.3 |
| Embodiment 4 | 0.4 |
| Embodiment 5 | 0.3 |
| Reference examples 1 | 0.6 |
Utilize following standard to judge skin irritation according to index (P.I.I).
0≤P.I.I.≤2: weak stimulation
2＜P.I.I.≤5: moderate stimulates
5＜P.I.I.≤8: strong stimulation
The result shows, has with the composition of comparative examples 1 according to the composition of embodiment of the invention 1-5 and compares roughly the same or littler skin irritation, and wherein the composition of comparative examples 1 has been widely used as disinfectant, is foolproof therefore.
In addition, the composition of embodiment 1-5 also has with comparative examples 2-3 and compares identical or littler skin irritation.
＜antibacterial activity test 〉
Each experimental strain all utilizes Muller-Hinton meat soup 37 ℃ of incubated overnight, carry out the cultivation of going down to posterity for three times continuously, utilize sterilized distilled water that the optical density (OD) that the pre-culture of bacteria solution of gained is adjusted at the 660nm place is 0.3Abs then, so that counting is about 10
8Cfu/mL subsequently, further is diluted to 100 times with sterilized distilled water with this solution, makes counting for about 10
6Cfu/mL, thus the experiment bacterial suspension obtained.
Use experiment suspension, make 2 times of dilution series with sterilized distilled water, make for every kind of suspension in this series, Olanexidine concentration be 2 times to final experimental concentration, every kind of suspension 50 μ L in this series are assigned in the 8 row holes along the length direction of 96 hole micro plates, the order that makes progress with the concentration of minimum.50 μ L experiment bacterial suspension is assigned to distributed a kind of waiting to try in each hole of suspension, and mix immediately.Every kind of mixed reaction liquid is collected 10 μ L, and after the predetermined processing time, be injected in the SCDLP culture medium (the deactivation medium of disinfectant) in the hole that 200 μ L have been assigned to another 96 hole micro plate, mix to stop bactericidal activity, cultivated 48 hours at 37 ℃ then.
After the cultivation, with the naked eye judge from the turbidity of culture medium whether the bacterium each hole breeds, and becomes turbid to show that bacterium breeds, do not show not propagation of bacterium and do not become turbid.In the dilution series of experiment suspension, the Cmin that will not observe bacterial multiplication is as treating the minimal bactericidal concentration (MBC) of test solution body for the experiment bacterium.
Antibacterial activity test the results are shown in table 2 and 3.
Table 2
The MBC (μ g/mL) that handled in 10 seconds
| Experimental strain | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Reference examples 1 |
| Staphylococcus aureus FDA 209P | ≤7.81 | 31.3 | 62.5 | 62.5 | 31.3 | 5000 |
| MRSA clinical isolates C5414 | ≤7.81 | 31.3 | 31.3 | 15.6 | 62.5 | ＞5000 |
| Staphylococcus epidermidis ATCC 12228 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | 15.6 | 500 |
| Enterococcus faecalis NCTC 12201 (VRE) | ≤7.81 | 15.6 | ≤7.81 | 15.6 | 15.6 | ＞5000 |
| Colon bacillus NIHJ JC-2 | ≤7.81 | 15.6 | 15.6 | 15.6 | 15.6 | 2000 |
| Serratia marcescens IFO 12648 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | 5000 |
| Proteus mirabilis 1287 | ≤7.81 | 250 | ＞500 | ＞500 | ＞500 | ＞5000 |
| Onion bulkholderia cepasea IFO 14595 | ≤7.81 | ＞500 | ＞500 | ＞500 | ＞500 | ＞5000 |
Table 3
The MBC (μ g/mL) that handled in 180 seconds
| Experimental strain | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | Reference examples 1 |
| Staphylococcus aureus FDA 209P | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | 2000 |
| MRSA clinical isolates C5414 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ＞5000 |
| Staphylococcus epidermidis ATCC 12228 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 |
| Enterococcus faecalis NCTC 12201 (VRE) | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ＞5000 |
| Colon bacillus NIHJ JC-2 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | 31.3 |
| Serratia marcescens IFO 12648 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 |
| Proteus mirabilis 1287 | ≤7.81 | 15.6 | ≤7.81 | ≤7.81 | ≤7.81 | 1000 |
| Onion bulkholderia cepasea IFO 14595 | ≤7.81 | 125 | 31.3 | 62.5 | 62.5 | 5000 |
Shown in result in table 2 and 3, reveal wide antimicrobial spectrum according to the compositions table of embodiments of the invention 1-5, and show the bactericidal action stronger than traditional disinfectant.And shown in result in the table 2, even 10 seconds short time sterilization processing, these bactericidal actions also show very by force, and this is highly beneficial from actual use angle.
The solvability of OPB 2045 self is 0.02% at 0 ℃, and for example, under this concentration, bactericidal activity is subject to the influence of pH, serum, soap, temperature etc.Use composition of the present invention, the concentration of OPB 2045 improves, and has therefore eliminated this influence.
Test implementation example 1
For the composition [concentration of OPB 2045 is 0.1% (1000 μ g/mL)] of embodiment 2 with the aqueous solution of 0.02% (200 μ g/mL) OPB 2045 is only arranged, carry out the comparison of bactericidal activity (existing under the situation of 5% cow's serum) under the condition that organic matter pollutes.Staphylococcus aureus FDA209P, colon bacillus NIHJ JC-2 and pseudomonas aeruginosa ATCC10145 are as the experiment bacterium.The results are shown in table 4.
Table 4
| Bovine serum concentration (%) | The aqueous solution that has only OPB 2045 | Embodiment 2 (0.32%NP-10) | |||||
| 30 seconds | 1 minute | 3 minutes | 30 seconds | 1 minute | 3 minutes | ||
| Staphylococcus aureus FDA 209P | 0 5 | 25 ＞200 | 6.25 100 | ≤3.13 100 | 25 1000 | 12.5 100 | 12.5 100 |
| Colon bacillus NIHJ JC-2 | 0 5 | 6.25 ＞200 | ≤3.13 ＞200 | ≤3.13 ＞200 | 15.6 1000 | 7.81 1000 | 7.81 500 |
| Pseudomonas aeruginosa ATCC 10145 | 0 5 | 6.25 ＞200 | ≤3.13 ＞200 | ≤3.13 ＞200 | 6.25 1000 | ≤3.13 1000 | ≤3.13 1000 |
From these results, even find to exist under the organic situation, to compare with the aqueous solution that OPB 2045 is only arranged, the composition of embodiment 2 shows bactericidal activity in the shorter time, and therefore very practical.
Test implementation example 2
The skin of mouse back is polluted with staphylococcus aureus FDA209P, and the Disinfection Effect of each processed group shown in the comparison sheet 5.
Table 5
| Processed group (No.n=6) | Sterilize back 10 seconds (at once) | Sterilized back 2 hours | ||
| The survival bacterial population | Degerming rate (%) | The survival bacterial population | Degerming rate (%) | |
| Untreated fish group | 8.45×10 3 | 0 | 9.06×10 3 | 0 |
| Group with 70% Ethanol Treatment | 0 | 100 | 8.99×10 3 | 0.77 |
| Group with embodiment 1 compositions-treated | 0 | 100 | 4 | 99.9 |
| Group with embodiment 2 compositions-treated | 8 | 99.9 | 3 | 99.9 |
The result shows, shows 100% degerming rate with the group of 70% Ethanol Treatment with the group of embodiment 1 compositions-treated a moment (after 10 seconds) after the sterilization, shows 100% the degerming rate of being almost with the group of embodiment 2 compositions-treated.Yet, sterilize latter two hour, show 0.77% degerming rate with the group of 70% Ethanol Treatment, this approaches the situation of untreated fish group, promptly no longer observes bactericidal effect.In contrast, show at least 99.9% degerming rate respectively in sterilization latter two hour, promptly show high lasting bactericidal effect with the group of embodiment 1 and 2 compositions-treated.Even still observed this lasting bactericidal effect in back four hours in sterilization.
Invention III composition
EXAMPLE III-1
About 80ml water is joined 1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and 3.1g polyoxyethylene (POE (20)) dehydrated sorbitol mono-fatty acid ester (by Nikko Chemicals Co., Ltd. make) in, and mix and dissolve, with pH regulator to 5, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
EXAMPLE III-2
About 80ml water is joined 1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and the 7.4g DECAGLYCERYL MONOLAURATE (by Nikko Chemicals Co., Ltd. make) in, and mix and dissolve, with pH regulator to 5, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
EXAMPLE III-3
About 80ml water is joined 1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and in 4.9g polyoxyethylene (POE (the 7)) glyceryl cocoate (making) by Cognis Japan Ltd., and mix and dissolve, with pH regulator to 5, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
EXAMPLE III-4
About 80ml water is joined 1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and 4.8g polyoxyethylene (POE (7)) glycerine sad/decylate (making) by Cognis Japan Ltd. in, and mix and dissolve, with pH regulator to 5, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
EXAMPLE III-5
About 80ml water is joined 1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and in 11.1g polyoxyethylene (POE (120)) the methyl glucosamine dioleate (making) by Amerchol, and mix and dissolve, with pH regulator to 5, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
EXAMPLE III-6
About 80ml water is joined 1g OPB 2045 powder (Otsuka Pharmaceutical Co., Ltd.) and in the 9.1g alpha-cyclodextrin (making) by Hayashibara, and mix and dissolve, with pH regulator to 5, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
Even transferring postpone near 0 ℃ temperature, EXAMPLE III-1 aqueous solution of gained to the III-6 also remains clear, colorless, not precipitation.
Comparing embodiment III-1
About 80ml water is joined 50mg OPB 2045 (Otsuka Pharmaceutical Co., Ltd.) in and dissolve,, and then add entry with pH regulator to 6, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.(25 ℃ time solvability be 0.05W/V%)
Comparative examples III-1
About 80ml water is joined in the 20W/V% chlorhexidine gluconate aqueous solution (SumitomoPharmaceuticals Company Limited) of 2.5ml, with pH regulator to 6, and then add entry, obtaining the cumulative volume of 100mL, thereby obtain sterilization and/or bactericidal aqueous compositions.
＜antibacterial activity test 〉
Each experimental strain all utilizes Muller-Hinton meat soup 37 ℃ of incubated overnight, carry out the cultivation of going down to posterity for three times continuously, utilize sterilized distilled water that the optical density (OD) that the pre-culture of bacteria solution of gained is adjusted at the 660nm place is 0.3Abs then, so that counting is about 10
8Cfu/mL subsequently, further is diluted to 100 times with sterilized distilled water with this solution, makes counting for about 10
6Cfu/mL, thus the experiment bacterial suspension obtained.
Use experiment suspension, make 2 times of dilution series with sterilized distilled water, make for every kind of suspension in this series, Olanexidine concentration be 2 times to final experimental concentration, every kind of liquid 50 μ L in this series are assigned in the 8 row holes along the length direction of 96 hole micro plates, the order that makes progress with the concentration of minimum.50 μ L experiment bacterial solution is assigned to distributed in a kind of each hole for the treatment of the test solution body, and mix immediately.Every kind of mixed reaction suspension is collected 10 μ L, and after the predetermined processing time, be injected in the SCDLP culture medium (the deactivation medium of disinfectant) in the hole that 200 μ L have been assigned to another 96 hole micro plate, mix to stop bactericidal activity, cultivated 48 hours at 37 ℃ then.
After the cultivation, with the naked eye judge from the turbidity of culture medium whether the bacterium each hole breeds, and becomes turbid to show that bacterium breeds, do not show not propagation of bacterium and do not become turbid.In the dilution series of experiment suspension, the Cmin that will not observe bacterial multiplication is as treating the minimal bactericidal concentration (MBC) of test solution body for the experiment bacterium.Antibacterial activity test the results are shown in table 6 and 7.
Table 6 (MBC (μ g/mL)
| Experimental strain (exp:10 6CFU/mL) | Staphylococcus aureus FDA 209P | Staphylococcus epidermidis ATCC 12228 | Enterococcus faecalis NCTC 12201 | |||
| Processing time | 30 seconds | 3 minutes | 30 seconds | 3 minutes | 30 seconds | 3 minutes |
| Comparative Example I II-1 | 62.5 | 15.63 | 7.81 | 7.81 | 15.63 | 7.81 |
| EXAMPLE III-1 | 500 | 25 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 |
| EXAMPLE III-2 | 62.5 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 |
| EXAMPLE III-3 | 5000 | 2000 | 250 | ≤7.81 | 62.5 | 31.25 |
| EXAMPLE III-4 | 31.25 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 |
| EXAMPLE III-5 | 5000 | 2000 | 250 | ≤7.81 | 62.5 | 31.25 |
| EXAMPLE III-6 | 62.5 | ≤7.81 | ≤7.81 | ≤7.81 | 15.63 | ≤7.81 |
| Reference examples III-1 | 5000 | 2000 | 500 | ≤7.81 | ＞5000 | ＞5000 |
Table 7 (MBC (μ g/mL)
| Experimental strain (exp:10 6CFU/mL) | Colon bacillus NIHJ JC-2 | Serratia marcescens IFO 12648 | ||
| Processing time | 30 seconds | 3 minutes | 30 seconds | 3 minutes |
| Comparative Example I II-1 | 15.63 | 7.81 | 15.63 | 7.81 |
| EXAMPLE III-1 | 12.5 | ≤7.81 | 12.5 | ≤7.81 |
| EXAMPLE III-2 | 15.63 | ≤7.81 | ≤7.81 | ≤7.81 |
| EXAMPLE III-3 | 125 | 31.25 | 500 | ≤7.81 |
| EXAMPLE III-4 | ≤7.81 | ≤7.81 | ≤7.81 | ≤7.81 |
| EXAMPLE III-5 | 125 | 31.25 | 500 | ≤7.81 |
| EXAMPLE III-6 | 15.63 | 15.63 | ≤7.81 | ≤7.81 |
| Reference examples III-1 | 500 | 31.25 | 1000 | ≤7.81 |
Shown in result in table 6 and 7, compare with the liquid of comparing embodiment III-1, show wide antimicrobial spectrum according to the liquid of embodiments of the invention III-1 to III-6, and show than the stronger bactericidal action of traditional disinfectant (comparative examples III-1).And even 30 seconds short period sterilization processing, these bactericidal actions also show very by force, and this is highly beneficial from actual use angle.
OPB 2045 is 0.02% from the solvability in water at 0 ℃, and for example, under this concentration, bactericidal activity is subject to the influence of pH, serum, soap, temperature etc.Use composition of the present invention, the concentration of OPB 2045 improves, and has therefore eliminated this influence.
Claims (17)
1. sterilization and/or bactericidal aqueous compositions, the Olanexidine acid-addition salts and the concentration that contain concentration and be 0.05-0.5W/V% are the alcohol of 20-80W/V%, and do not contain any surfactant.
2. according to the sterilization and/or the bactericidal aqueous compositions of claim 1, the concentration of wherein said alcohol in composition is 30-60W/V%.
3. sterilize and/or bactericidal aqueous compositions for one kind, contain Olanexidine acid-addition salts and at least a component that is selected from ester group non-ionic surface active agent and cyclic oligosaccharide.
4. according to the sterilization and/or the bactericidal aqueous compositions of claim 3, wherein said ester group non-ionic surface active agent is to be selected from (i) polyoxyethylene sorbitan fatty acid esters, (ii) polyglyceryl fatty acid ester, (iii) the polyoxyethylene fatty acid glyceride and the (iv) at least a component of Glucam E-10 fatty acid ester.
5. according to the sterilization and/or the bactericidal aqueous compositions of claim 4, wherein said polyoxyethylene sorbitan fatty acid esters is the represented compound of general formula (3):
R wherein
11Expression has the alkyl of 10-20 carbon atom, and h, j and k are respectively the integer of 5-25.
6. according to the sterilization and/or the bactericidal aqueous compositions of claim 4, wherein said polyglyceryl fatty acid ester is the represented compound of general formula (4):
R wherein
21-R
25One of expression have the alkanoyl of 10-20 carbon atom, other (p+3) individual expression hydrogen atom, p is the integer of 2-12.
7. according to the sterilization and/or the bactericidal aqueous compositions of claim 4, wherein said polyoxyethylene fatty acid glyceride is the represented compound of general formula (5):
R wherein
31Expression has the alkyl of 6-16 carbon atom, and q is the integer of 4-30.
8. according to the sterilization and/or the bactericidal aqueous compositions of claim 4, wherein said Glucam E-10 fatty acid ester is the represented compound of general formula (6):
R wherein
41Expression has the alkyl of 15-20 carbon atom, and the summation of x and y is the integer of 20-160.
9. according to the sterilization and/or the bactericidal aqueous compositions of claim 3, wherein cyclic oligosaccharide is a cyclodextrin.
10. according to the sterilization and/or the bactericidal aqueous compositions of claim 3, wherein the concentration of Olanexidine acid-addition salts is 0.05-2.5W/V%, and the concentration of ester group non-ionic surface active agent is 0.1-10W/V%.
11. according to the sterilization and/or the bactericidal aqueous compositions of claim 3, wherein the concentration of Olanexidine acid-addition salts is 0.1-2.5W/V%, the concentration of ester group non-ionic surface active agent is 0.1-10W/V%.
12. according to the sterilization and/or the bactericidal aqueous compositions of claim 3, wherein the concentration of Olanexidine acid-addition salts is 0.05-1W/V%, the concentration of cyclic oligosaccharide is 0.1-10W/V%.
13. according to the sterilization and/or the bactericidal aqueous compositions of claim 3, wherein the concentration of Olanexidine acid-addition salts is 0.1-1W/V%, the concentration of cyclic oligosaccharide is 0.1-10W/V%.
14. according to the sterilization and/or the bactericidal aqueous compositions of claim 3, wherein said composition also contains alcohol.
15. according to the sterilization and/or the bactericidal aqueous compositions of claim 14, the concentration of wherein said alcohol in composition is 20-80W/V%.
16. give object sterilization or disinfectant method, comprise described object is contacted with the sterilization and/or the bactericidal aqueous compositions according to claim 1 or 3 of effective dose for one kind.
17. the purposes that is used for sterilization or sterilization according to the sterilization and/or the bactericidal aqueous compositions of claim 1 or 3.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003151207 | 2003-05-28 | ||
| JP2003151207A JP4541661B2 (en) | 2003-05-28 | 2003-05-28 | Disinfecting and / or disinfecting composition |
| JP2003188360 | 2003-06-30 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2004800146135A Division CN1794915A (en) | 2003-05-28 | 2004-05-25 | Aqueous compositions for disinfection and/or sterilization |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101011058A true CN101011058A (en) | 2007-08-08 |
Family
ID=34046806
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200710087510 Pending CN101011058A (en) | 2003-05-28 | 2004-05-25 | Disinfectant and/or bactericidal aqueous compositions |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JP4541661B2 (en) |
| CN (1) | CN101011058A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102099329B (en) * | 2008-05-19 | 2015-02-11 | 大冢制药美国公司 | Method and apparatus for preparing a solution of a shear sensitive material |
| CN107646862A (en) * | 2017-10-27 | 2018-02-02 | 济南博世医药科技有限公司 | Aqueous olanexidine solution based on ascorbic acid and its preparation method and application |
| CN110494132A (en) * | 2017-04-19 | 2019-11-22 | 株式会社大塚制药工场 | Anti-inflammatory agent |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5268982B2 (en) * | 2003-05-28 | 2013-08-21 | 大塚製薬株式会社 | Oranexidine aqueous solution, its preparation method and disinfectant |
| JP4526300B2 (en) * | 2003-05-28 | 2010-08-18 | 大塚製薬株式会社 | Oranexidine aqueous solution, its preparation method and disinfectant |
| AU2019307996B2 (en) * | 2018-07-18 | 2024-03-14 | Otsuka Pharmaceutical Factory, Inc. | Disinfectant composition |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2662343B2 (en) * | 1991-06-19 | 1997-10-08 | 大塚製薬株式会社 | Monobiguanide derivative and disinfectant containing this derivative |
-
2003
- 2003-05-28 JP JP2003151207A patent/JP4541661B2/en not_active Expired - Fee Related
-
2004
- 2004-05-25 CN CN 200710087510 patent/CN101011058A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102099329B (en) * | 2008-05-19 | 2015-02-11 | 大冢制药美国公司 | Method and apparatus for preparing a solution of a shear sensitive material |
| CN110494132A (en) * | 2017-04-19 | 2019-11-22 | 株式会社大塚制药工场 | Anti-inflammatory agent |
| CN107646862A (en) * | 2017-10-27 | 2018-02-02 | 济南博世医药科技有限公司 | Aqueous olanexidine solution based on ascorbic acid and its preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004352635A (en) | 2004-12-16 |
| JP4541661B2 (en) | 2010-09-08 |
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