CN108969534A - The preparation of chlorhexidine iodine complexing nano object - Google Patents
The preparation of chlorhexidine iodine complexing nano object Download PDFInfo
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Abstract
The invention discloses the preparations of chlorhexidine iodine complexing nano object, the present invention prepares the component that chlorhexidine iodine complexing nano object uses and its weight percent is as follows: Chlorhexidine 5-35%, iodine 3-30%, potassium iodide 2-18%, surfactant 10-30%, cosurfactant 5-15%, organic solvent 25-45%, purified water 4-30%.Prepared by the method chlorhexidine iodine complexing nano object particle diameter distribution is relatively narrow, it is easy to control, it can be easier to obtain the nanoparticle of uniform particle sizes, by selecting different surfaces bioactive molecule to wrap up and modify particle, make to be not easy to coalesce between particle, reaches good stability.Be added to skin with common chlorhexidine iodine complex compound using chlorhexidine iodine complexing nano object of the invention, in mucous membrane sterilized sanitary accessories compared with, product stability is good, and irritation is small, and antibacterial wide spectrum, disinfection is strong, safe and convenient to use.
Description
Technical field
The invention belongs to medical disinfection fields, and in particular to prepare chlorhexidine iodine complexing nano object using microemulsion method.
Background technique
Micro-emulsion method for preparing nano particle is a kind of simple and easy and has the new method with intelligence, is to grind at present
Study carefully hot spot, it be using two kinds of immiscible solvents formed under the action of surfactant it is thermodynamically stable, respectively to same
Property, appearance transparent or translucent uniform liquid dispersion system (dispersed phase diameter is about 1-100nm), i.e. microemulsion, then
Solid phase is precipitated from microemulsion to prepare the nano-powder of certain partial size.Microemulsion usually by surfactant, help surface living
Property agent, solvent and water composition.Two kinds of immiscible continuous medias are divided by surfactant parents' molecule in this system
Short space forms microreactor, and size can be controlled in nano-scale range, and reactant reacts in system generates solid phase grain
Son.Due to microemulsion can partial size to nano material and stability accurately controlled, limit nucleation, the life of nanoparticle
The processes such as long, coalescence, reunion, so that the nanoparticle formed is enclosed with layer of surface activating agent, and have certain condensed state knot
Structure.
Chlorhexidine iodine is the complex compound of Chlorhexidine and iodine, and antibacterial wide spectrum, sterilization rate is high, and safety and stability, Disinfection Effect is better than
The Chlorhexidine and iodine of folk prescription are a kind of ideal high-efficiency low-toxicity disinfectant for external use.Most common method is Direct precipitation
Method, can not prepare that broad-spectrum, sterilization speed are fast, efficiency time is long, the preparation of low stimulation.Such as medicine Leader in August, 2012
The preparation of chlorhexidine iodine complex compound is mentioned in the preparation of the phase periodical chlorhexidine iodine solution of volume 31 the 8th and preliminarily stabilised Journal of Sex Research,
Iodine aqueous solution is mixed with chlorhexidine acetate aqueous solution and is sufficiently stirred, it is static to be obtained by filtration sediment, vacuum drying obtain chlorine oneself
Determine iodo-complexes, resulting chlorhexidine iodine complex compound partial size is big, cannot reach between Chlorhexidine and iodine and combine closely, with skin parent
It is poor with power.
Summary of the invention
The present invention be directed to existing chlorhexidine iodine preparation shortcoming, provide a kind of stability it is good, it is quick and durable sterilization, it is right
The preparation of the small chlorhexidine iodine complexing nano object of skin irritation.
The present invention prepares chlorhexidine iodine complexing nano object using microemulsion method, the Chlorhexidine molecule and iodine as cation
With I3-Three anion of iodine existing for form realizes that space structure is combined closely, and this special chemical structure makes holding for Chlorhexidine
Long bactericidal effect and iodine quick release free-iodine quick sterilization are acted on and being effectively combined, and the more target position of pathogen are attacked in realization
Synergy is hit, the bactericidal effect of chlorhexidine iodine disinfectant is effectively raised.
The thimerosal prepared using the chlorhexidine iodine complexing nano object, it is good with skin compatibility, it is small to the irritation of skin.
Compared with traditional preparation method, the particle of microemulsion method preparation is not easy to coalesce, and stability is good, and size is controllable, and partial size is ultra-fine, point
It is good to dissipate property.
The present invention provides a kind of preparation of chlorhexidine iodine complexing nano object, and the component and its weight percent of use are as follows:
Chlorhexidine of the present invention: the weight ratio of iodine is 1:0.2-5.
Chlorhexidine of the present invention is chlorhexidine acetate or chlorhexidine gluconate.
Surfactant of the present invention is Tween-80, poloxamer188 or ethoxylated dodecyl alcohol.
Cosurfactant n-butanol, n-hexyl alcohol or n-amyl alcohol of the present invention.
Organic solvent of the present invention is hexamethylene, isooctane or n-hexane.
The preparation of chlorhexidine iodine complexing nano object of the present invention, comprising the following steps:
(1) iodine, potassium iodide are weighed, dissolution is added water and stirred, 20% iodine solution is made；
(2) Chlorhexidine is weighed, water is added, 20% chlorhexidine is made in stirring and dissolving；
(3) surfactant, cosurfactant are weighed, is added in organic solvent, is stirred and evenly mixed, organic phase is made；
(4) organic phase is divided into two parts.Iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Another
In plus 20% chlorhexidine, stirring and emulsifying, be made Chlorhexidine microemulsion；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continue stirring 40~
60min, after separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) by sediment be put into vacuum dryer in 70-80 DEG C drying 2-3 hours, obtain the chlorhexidine iodine
Complexing nano object.
The present invention uses microemulsion method, will prepare Chlorhexidine microemulsion and iodine microemulsion respectively first, and formation two is small
" pond " monolayer interface composed by surfactant and cosurfactant surround and form water-in-oil microemulsion
Drop, size control is between tens to several hundred angstroms, under this special microenvironment (or " microreactor "), by two kinds
Microemulsion is quickly uniformly mixed, and since micro emulsion drop is ceaselessly making Brownian movement, variable grain is when colliding with each other, group
Mutually penetrated at the surfactant at interface and the hydrocarbon chain of cosurfactant, the substance in " pond " can pass through interface into
Enter another micro emulsion drop, i.e. Chlorhexidine passes through interface and enters Water-In-Oil iodine micro emulsion drop, formed in microemulsion stable chlorine oneself
Determine iodine nanometer micro-emulsion drop, separates chlorhexidine iodine nanometer micro-emulsion drop with microemulsion by ultracentrifugation separation, with organic molten
Agent washes away the oil and surfactant of microparticle surfaces, and solid chlorhexidine iodine complexing nano object is made in last vacuum drying.
The present invention is compared with traditional preparation methods, and the particle of microemulsion preparation is not easy to coalesce, and size is controllable, and partial size is ultra-fine small
In 60nm, stability is good, good dispersion, using as cation Chlorhexidine molecule and iodine with I3-Iodine three existing for form it is negative from
Son realizes that space structure is combined closely, and obtains this special chemical structure, keeps the lasting bactericidal effect of Chlorhexidine and iodine quick
Release free-iodine quick sterilization, which acts on, to be effectively combined, and realizes the attack synergy to the more target position of pathogen, effectively
Improve the bactericidal effect of chlorhexidine iodine disinfectant.The thimerosal prepared using the chlorhexidine iodine complexing nano object, with skin parent
It is good with property, it is small to the irritation of skin.
The chlorhexidine iodine thimerosal of chlorhexidine iodine complexing nano object configuration prepared by the present invention is compared to conventional method preparation
The chlorhexidine iodine thimerosal of chlorhexidine iodine complex compound configuration can faster reach disinfection, under 0.5min action time, to gold
Staphylococcus aureus, Candida albicans, Escherichia coli, pseudomonas aeruginosa averagely kill logarithm it is equal > 5.00, and conventional method
The chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration of preparation reads staphylococcus aureus, white under 2min effect
Pearl bacterium, Escherichia coli, pseudomonas aeruginosa are not up to bactericidal effect.
Chlorhexidine iodine complexing nano object prepared by the present invention can be used for preparing all kinds of skins, mucous membrane thimerosal, prepare
Thimerosal stability is good, sterilizes quick and durable, small to skin irritation advantage.
The present invention is primary with the alcohol-containing chlorhexidine iodine thimerosal of chlorhexidine iodine complexing nano object configuration prepared by microemulsion method
Each point of observation rabbit highest skin wound repair integral mean value of intact skin stimulation test is 0.3, is belonged to nonirritant；And with normal
Intact skin stimulation test of alcohol-containing chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration of rule method preparation is respectively observed
Point rabbit highest skin wound repair integral mean value is 0.7, belongs to subexcite.
The present invention is primary with the alcohol-containing chlorhexidine iodine thimerosal of chlorhexidine iodine complexing nano object configuration prepared by microemulsion method
Each point of observation rabbit highest skin wound repair integral mean value of damaged skin stimulation test is 0.3, is belonged to nonirritant；And with normal
Intact skin stimulation test of alcohol-containing chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration of rule method preparation is respectively observed
Point rabbit highest skin wound repair integral mean value is 1.7, belongs to subexcite.
The not alcohol-containing chlorhexidine iodine thimerosal one for the chlorhexidine iodine complexing nano object configuration that the present invention is prepared with microemulsion method
Secondary each point of observation rabbit highest skin wound repair integral mean value of intact skin stimulation test is 0, is belonged to nonirritant；And with normal
Intact skin stimulation test of not alcohol-containing chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration of rule method preparation is respectively seen
Examining a rabbit highest skin wound repair integral mean value is 0.7, belongs to subexcite.
The not alcohol-containing chlorhexidine iodine thimerosal one for the chlorhexidine iodine complexing nano object configuration that the present invention is prepared with microemulsion method
Secondary each point of observation rabbit highest skin wound repair integral mean value of damaged skin stimulation test is 0.3, is belonged to nonirritant；And with
Intact skin stimulation test of not alcohol-containing chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration of conventional method preparation is each
Point of observation rabbit highest skin wound repair integral mean value is 1, belongs to subexcite.
Prepared by the method chlorhexidine iodine complexing nano object particle diameter distribution is relatively narrow, easy to control, can be easier to obtain grain
The uniform nanoparticle of diameter makes to be not easy between particle by selecting different surfaces bioactive molecule to wrap up and modify particle
Coalescence, reaches good stability.
Skin is added to using chlorhexidine iodine complexing nano object of the invention and common chlorhexidine iodine complex compound, mucous membrane sterilizes
It is compared in amenities, product stability is good, and irritation is small, and antibacterial wide spectrum, disinfection is strong, safe and convenient to use.
Detailed description of the invention
Attached drawing is preparation process schematic diagram according to the present invention.
Specific embodiment
It elaborates below with reference to embodiment to specific embodiment provided by the invention.
Embodiment 1
The preparation process of the chlorhexidine iodine complexing nano object is as follows:
(1) iodine 15g, potassium iodide 9g are weighed, purified water 51g is added, 20% iodine solution is made in stirring and dissolving；
(2) chlorhexidine acetate 22g is weighed, purified water 88g is added, 20% chlorhexidine is made in stirring and dissolving；
(3) Tween-80 76g, n-hexyl alcohol 54g are weighed, is added in isooctane 180g, stirs and evenly mixs, organic phase is made；
(4) organic phase is divided into two parts, iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Another
In plus 20% chlorhexidine, stirring and emulsifying, be made Chlorhexidine microemulsion；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continues to stir 50min,
After separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) sediment is put into vacuum dryer and is dried 2.5 hours in 75 DEG C, obtain the chlorhexidine iodine nanometer
Complex compound.
It takes chlorhexidine iodine complexing nano object 4.0g obtained by the present embodiment to prepare thimerosal, 95% ethyl alcohol 487g is added,
Purified water is mended to 1000ml, is stirred evenly, pH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is 0.15%,
Chlorhexidine acetate 0.22%, ethanol content 60%.
Embodiment 2
The preparation process of the chlorhexidine iodine complexing nano object is as follows:
(1) iodine 30g, potassium iodide 18g are weighed, purified water 102g is added, 20% iodine solution is made in stirring and dissolving；
(2) 20% chlorhexidine gluconate solution 75g is weighed；
(3) ethoxylated dodecyl alcohol 124g, n-butanol 60g are weighed, is added in hexamethylene 220g, stirs and evenly mixs, is made
At organic phase；
(4) organic phase is divided into two parts, iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Another
In plus 20% chlorhexidine, stirring and emulsifying, be made Chlorhexidine microemulsion；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continues to stir 50min,
After separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) sediment is put into vacuum dryer and is dried 2.5 hours in 75 DEG C, obtain the chlorhexidine iodine nanometer
Complex compound.
It takes chlorhexidine iodine complexing nano object 4.8g obtained by the present embodiment to prepare thimerosal, aliphatic alcohol polyethenoxy is added
Ether 60g mends purified water to 1000ml, stirs evenly, pH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is
0.3%, chlorhexidine gluconate content 0.15%.
Embodiment 3
The preparation process of the chlorhexidine iodine complexing nano object is as follows:
(1) iodine 45g, potassium iodide 27g are weighed, purified water 153g is added, 20% iodine solution is made in stirring and dissolving；
(2) chlorhexidine acetate 12g is weighed, purified water 48g is added, 20% chlorhexidine is made in stirring and dissolving；
(3) 140g poloxamer188, n-amyl alcohol 86g are weighed, is added in isooctane 350g, stirs and evenly mixs, is made organic
Phase；
(4) organic phase is divided into two parts, iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Another
In plus 20% chlorhexidine, stirring and emulsifying, be made Chlorhexidine microemulsion；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continues to stir 50min,
After separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) sediment is put into vacuum dryer and is dried 2.5 hours in 75 DEG C, obtain the chlorhexidine iodine nanometer
Complex compound.
It takes chlorhexidine iodine complexing nano object 6.0g obtained by the present embodiment to prepare, fatty alcohol polyoxyethylene ether 65g is added,
Purified water is mended to 1000ml, is stirred evenly, PH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is 0.45%,
Chlorhexidine acetate 0.12%.
Embodiment 4
The preparation process of the chlorhexidine iodine complexing nano object is as follows:
(1) iodine 10g, potassium iodide 6g are weighed, purified water 34g is added, 20% iodine solution is made in stirring and dissolving；
(2) 20% chlorhexidine gluconate solution 225g is weighed；
(3) 110g Tween-80, n-hexyl alcohol 72g are weighed, is added in isooctane 360g, stirs and evenly mixs, organic phase is made；
(4) organic phase is divided into two parts, iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Another
In plus 20% chlorhexidine, stirring and emulsifying, be made Chlorhexidine microemulsion；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continues to stir 50min,
After separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) sediment is put into vacuum dryer and is dried 2.5 hours in 75 DEG C, obtain the chlorhexidine iodine nanometer
Complex compound.
It takes chlorhexidine iodine complexing nano object 5.8g obtained by the present embodiment to prepare thimerosal, 95% ethyl alcohol 527g is added,
Purified water is mended to 1000ml, is stirred evenly, PH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is 0.1%,
Chlorhexidine gluconate content 0.45%, ethanol content 65%.
Embodiment 5
The preparation process of the chlorhexidine iodine complexing nano object is as follows:
(1) iodine 5g, potassium iodide 3g are weighed, purified water 17g is added, 20% iodine solution is made in stirring and dissolving；
(2) 20% chlorhexidine gluconate solution 100g is weighed；
(3) 90g poloxamer188, n-hexyl alcohol 50g are weighed, is added in hexamethylene 144g, stirs and evenly mixs, is made organic
Phase；
(4) organic phase is divided into two parts, iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Another
In plus 20% chlorhexidine, stirring and emulsifying, be made Chlorhexidine microemulsion；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continues to stir 50min,
After separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) sediment is put into vacuum dryer and is dried 2.5 hours in 75 DEG C, obtain the chlorhexidine iodine nanometer
Complex compound.
It takes chlorhexidine iodine complexing nano object 2.6g obtained by the present embodiment to prepare thimerosal, aliphatic alcohol polyethenoxy is added
Ether 30g mends purified water to 1000ml, stirs evenly, PH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is
0.05%, chlorhexidine gluconate content 0.2%.
Embodiment 6
The preparation process of the chlorhexidine iodine complexing nano object is as follows:
(1) iodine 15g, potassium iodide 9g are weighed, purified water 51g is added, 20% iodine solution is made in stirring and dissolving；
(2) 20% chlorhexidine gluconate solution 25g is weighed；
(3) ethoxylated dodecyl alcohol 46g, n-butanol 26g are weighed, is added in n-hexane 78g, stirs and evenly mixs, be made
Organic phase；
(4) organic phase is divided into two parts, iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Another
In plus 20% chlorhexidine, stirring and emulsifying, be made Chlorhexidine microemulsion；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continues to stir 50min,
After separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) sediment is put into vacuum dryer and is dried 2.5 hours in 75 DEG C, obtain the chlorhexidine iodine nanometer
Complex compound.
It takes chlorhexidine iodine complexing nano object 2.1g obtained by the present embodiment to prepare thimerosal, 95% ethyl alcohol 447g is added,
Purified water is mended to 1000ml, is stirred evenly, PH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is 0.15%,
Chlorhexidine gluconate content 0.05%, ethanol content 55%.
Embodiment 7
The chlorhexidine iodine complexing nano object 0.1g for taking above-described embodiment 1-6 to prepare is diluted with water to 100ml, stirs well and takes 10ml
It being put into laser particle size analyzer sample cell, data is repeated several times, the average grain diameter for measuring the above various embodiments is 30-35nm,
Thus polydispersity coefficient 0.2-0.3 illustrates that particle diameter is tiny, good dispersion, and stability is good.
Embodiment 8
The chlorhexidine iodine thimerosal for taking above-described embodiment 1-6 to prepare, according to Ministry of Health of the People's Republic of China's version in 2002
" disinfection technology standard " carries out germicidal experiment, with chlorhexidine iodine thimerosal suspension quantitative bacteric idal experiment manufactured in the present embodiment
Method puts down staphylococcus aureus, Candida albicans, Escherichia coli, pseudomonas aeruginosa under the action time of 30s
Kill logarithm > 5.00.
Embodiment 9
The chlorhexidine iodine thimerosal for taking above-described embodiment 1-6 to prepare disappears according to European Union's sterilizing test standard EN14476 chemistry
The test of the Viral Quantification suspension of chemosterilant used in toxic agent and preservative physianthropy and preservative, convection current are susceptible
The killing Experimental Comparison of malicious H5N1, norovirus (Norovirus), under the action time of 0.5min, infected by influenza H5N1,
Norovirus (Norovirus) averagely kill logarithm it is equal > 5.00.
Embodiment 10
The chlorhexidine iodine thimerosal for taking above-described embodiment 1-6 to prepare, according to Ministry of Health of the People's Republic of China's version in 2002
" disinfection technology standard " carries out skin irritation test and vaginal mucosa irritation test, through multiple skin irritatin, vaginal mucosa
Irritant test, the thimerosal that the chlorhexidine iodine complex compound is prepared as the result is shown are non-stimulated to skin, vaginal mucosa stimulus intensity
Property.
Embodiment 11
The chlorhexidine iodine thimerosal for taking above-described embodiment 1-6 to prepare, according to version " disinfection technology standard " second in 2002
2.3.1 is divided to carry out acute oral toxicity test, every 20g weight intragastric administration on mice 100mg is observed continuously 14 days.As a result in 14 days
The internal organs of mouse are dissected and observed without dead number of cases in mice displayed no abnormal phenomenon, no abnormal, that is, show the chlorhexidine iodine
The thimerosal of complexing nano object configuration is actually safe and non-toxic.
Embodiment 12
1. using micro-emulsion method for preparing nano complex compound of the invention:
The preparation process of chlorhexidine iodine complexing nano object is as follows:
(1) iodine 15g, potassium iodide 9g are weighed, purified water 51g is added, 20% iodine solution is made in stirring and dissolving；
(2) 20% chlorhexidine gluconate solution 25g is weighed；
(3) ethoxylated dodecyl alcohol 46g, n-butanol 26g are weighed, is added in n-hexane 78g, stirs and evenly mixs, be made
Organic phase；
(4) organic phase is divided into two parts, iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Another
In plus 20% chlorhexidine, stirring and emulsifying, be made Chlorhexidine microemulsion；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continues to stir 50min,
After separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) sediment is put into vacuum dryer and is dried 2.5 hours in 75 DEG C, obtain the chlorhexidine iodine nanometer
Complex compound.
2. preparing chlorhexidine iodine complex compound using conventional method:
The preparation process of chlorhexidine iodine complex compound is as follows:
(1) (1) weighs iodine 15g, potassium iodide 9g, adds purified water 51g, and 20% iodine solution is made in stirring and dissolving；
(2) 20% chlorhexidine gluconate solution 25g is weighed；
(3) iodine solution of above-mentioned steps preparation and chlorhexidine are added in closed configuration filling, are stirred and evenly mixed, homogeneous 6
Minute；60 DEG C sealed thermal insulating 1 hour, filtering, by sediment be put into vacuum dryer in 75 DEG C dry 2.5 hours, obtain
The chlorhexidine iodine complex compound.
It takes chlorhexidine iodine complex compound 2.1g obtained by above two method to prepare thimerosal, 95% ethyl alcohol 447g is added,
Purified water is mended to 1000ml, is stirred evenly, PH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is 0.15%,
Chlorhexidine gluconate content 0.05%, ethanol content 55%.Take the chlorhexidine iodine complexing nano object of above two method preparation
The chlorhexidine iodine thimerosal of preparation kill according to Ministry of Health of the People's Republic of China 2002 version " disinfection technology standard " micro-
Biologic test has carried out comparative test to staphylococcus aureus, Candida albicans, Escherichia coli, pseudomonas aeruginosa.Specifically
Data such as the following table 1, wherein with the chlorhexidine iodine thimerosal of the chlorhexidine iodine complexing nano object configuration of microemulsion method preparation for A liquid,
The chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration prepared in conventional manner is B liquid.
1 two kinds of chlorhexidine iodine thimerosal Guantitative bactericidal tests of table
It takes chlorhexidine iodine complex compound 2.1g obtained by above two method to prepare thimerosal, aliphatic alcohol polyethenoxy is added
Ether 28g mends purified water to 1000ml, stirs evenly, PH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is
0.15%, chlorhexidine gluconate content 0.05% takes the chlorhexidine iodine complexing nano object preparation of above two method preparation
Chlorhexidine iodine thimerosal carries out killing microorganism examination according to Ministry of Health of the People's Republic of China 2002 version " disinfection technology standard "
It tests, comparative test has been carried out to staphylococcus aureus, Candida albicans, Escherichia coli, pseudomonas aeruginosa.Specific data are such as
The following table 2, wherein with the chlorhexidine iodine thimerosal of the chlorhexidine iodine complexing nano object configuration of microemulsion method preparation for A liquid, with routine
The chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration of method preparation is B liquid.
2 two kinds of chlorhexidine iodine thimerosal Guantitative bactericidal tests of table
It can be seen from the above experimental result in same sterilization component and content, Chlorhexidine prepared by the present invention
Chlorhexidine of the chlorhexidine iodine thimerosal of iodine complexing nano object configuration compared to the chlorhexidine iodine complex compound configuration of conventional method preparation
Iodic disinfecting liquid can faster reach disinfection, under 0.5min action time, to staphylococcus aureus, Candida albicans, big
Enterobacteria, pseudomonas aeruginosa averagely kill logarithm it is equal > 5.00, and conventional method preparation chlorhexidine iodine complex compound configuration
Chlorhexidine iodine thimerosal, under 2min effect, to staphylococcus aureus, Candida albicans, Escherichia coli, pseudomonas aeruginosa
It is not up to bactericidal effect.
Embodiment 13
1. using micro-emulsion method for preparing nano complex compound
The preparation process of chlorhexidine iodine complexing nano object is as follows:
(1) iodine 15g, potassium iodide 9g are weighed, purified water 51g is added, 20% iodine solution is made in stirring and dissolving；
(2) 20% chlorhexidine gluconate solution 25g is weighed；
(3) ethoxylated dodecyl alcohol 46g, n-butanol 26g are weighed, is added in n-hexane 78g, stirs and evenly mixs, be made
Organic phase；
(4) organic phase is divided into two parts, iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Another
In plus 20% chlorhexidine, stirring and emulsifying, be made Chlorhexidine microemulsion；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continues to stir 50min,
After separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) sediment is put into vacuum dryer and is dried 2.5 hours in 75 DEG C, obtain the chlorhexidine iodine nanometer
Complex compound.
2. preparing chlorhexidine iodine complex compound using conventional method:
The preparation process of chlorhexidine iodine complex compound is as follows:
(1) iodine 15g, potassium iodide 9g are weighed, purified water 51g is added, 20% iodine solution is made in stirring and dissolving；
(2) 20% chlorhexidine gluconate solution 25g is weighed；
(3) iodine solution of above-mentioned steps preparation and chlorhexidine are added in closed configuration filling, are stirred and evenly mixed, homogeneous 6
Minute；60 DEG C sealed thermal insulating 1 hour, filtering, by sediment be put into vacuum dryer in 75 DEG C dry 2.5 hours, obtain
The chlorhexidine iodine complex compound.
It takes chlorhexidine iodine complex compound 2.1g obtained by above two method to prepare thimerosal, 95% ethyl alcohol 447g is added,
Purified water is mended to 1000ml, is stirred evenly, PH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is 0.15%,
Chlorhexidine gluconate content 0.05%, ethanol content 55%.
The chlorhexidine iodine thimerosal for taking the chlorhexidine iodine complexing nano object preparation of above two method preparation, according to middle Chinese
The Ministry of Public Health of people republic version " disinfection technology standard " entry 2.3.3 in 2002, which carries out an intact skin, stimulates comparative test, tool
Volume data such as the following table 3；It is carried out according to Ministry of Health of the People's Republic of China version " disinfection technology standard " entry 2.3.3 in 2002 primary
Damaged skin stimulates comparative test, specific data such as the following table 4；Wherein matched with chlorhexidine iodine complexing nano object prepared by microemulsion method
The alcohol-containing chlorhexidine iodine thimerosal set is sample 1, the alcohol-containing chlorhexidine iodine of the chlorhexidine iodine complex compound configuration prepared in conventional manner
Thimerosal is sample 2, using the skin of the other side removal rabbit hair as control.
Disposable (complete) the skin wound repair scoring of 3 rabbit of table
As can be seen from the above results, with the alcohol-containing Chlorhexidine of the chlorhexidine iodine complexing nano object configuration of microemulsion method preparation
Each point of observation rabbit highest skin wound repair integral mean value of intact skin stimulation test of iodic disinfecting liquid is 0.3, belongs to nothing
Irritation；
Intact skin thorn of alcohol-containing chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration prepared in conventional manner
Swashing each point of observation rabbit highest skin wound repair integral mean value of experiment is 0.7, belongs to subexcite.
The damaged skin stimulate the reaction scoring of 4 rabbit of table
As can be seen from the above results, with the alcohol-containing Chlorhexidine of the chlorhexidine iodine complexing nano object configuration of microemulsion method preparation
Each point of observation rabbit highest skin wound repair integral mean value of damaged skin stimulation test of iodic disinfecting liquid is 0.3, belongs to nothing
Irritation；
Intact skin thorn of alcohol-containing chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration prepared in conventional manner
Swashing each point of observation rabbit highest skin wound repair integral mean value of experiment is 1.7, belongs to subexcite.
It takes chlorhexidine iodine complex compound 2.1g obtained by above two method to prepare thimerosal, aliphatic alcohol polyethenoxy is added
Ether 28g mends purified water to 1000ml, stirs evenly, PH is adjusted to 3.5, and gained thimerosal major antibacterial ingredient available iodine content is
0.15%, chlorhexidine gluconate content 0.05%.
The chlorhexidine iodine thimerosal for taking the chlorhexidine iodine complexing nano object preparation of above two method preparation, according to middle Chinese
The Ministry of Public Health of people republic version " disinfection technology standard " entry 2.3.3 in 2002, which carries out an intact skin, stimulates comparative test, tool
Volume data such as the following table 5；It is carried out according to Ministry of Health of the People's Republic of China version " disinfection technology standard " entry 2.3.3 in 2002 primary
Damaged skin stimulates comparative test, specific data such as the following table 6；Wherein matched with chlorhexidine iodine complexing nano object prepared by microemulsion method
The not alcohol-containing chlorhexidine iodine thimerosal set be sample 1, prepare in conventional manner chlorhexidine iodine complex compound configuration not alcohol-containing chlorine oneself
Determining iodic disinfecting liquid is sample 2, using the skin of the other side removal rabbit hair as control.
Primary (complete) the skin wound repair scoring of 5 rabbit of table
As can be seen from the above results, with microemulsion method preparation chlorhexidine iodine complexing nano object configuration not alcohol-containing chlorine oneself
Determining each point of observation rabbit highest skin wound repair integral mean value of intact skin stimulation test of iodic disinfecting liquid is 0, belongs to nothing
Irritation；
Intact skin of not alcohol-containing chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration prepared in conventional manner
Each point of observation rabbit highest skin wound repair integral mean value of stimulation test is 0.7, belongs to subexcite.
The damaged skin stimulate the reaction scoring of 6 rabbit of table
As can be seen from the above results, with microemulsion method preparation chlorhexidine iodine complexing nano object configuration not alcohol-containing chlorine oneself
Determining each point of observation rabbit highest skin wound repair integral mean value of damaged skin stimulation test of iodic disinfecting liquid is 0.3, is belonged to
It is nonirritant；
Intact skin of not alcohol-containing chlorhexidine iodine thimerosal of the chlorhexidine iodine complex compound configuration prepared in conventional manner
Each point of observation rabbit highest skin wound repair integral mean value of stimulation test is 1, belongs to subexcite.
The present invention is not easy to coalesce using the particle of microemulsion preparation, and size is controllable, and partial size is ultra-fine to be less than 60nm, stability
Good, good dispersion is wrapped up and is modified to particle by selection different surfaces bioactive molecule, makes to be not easy to coalesce between particle,
Reach good stability.Using as cation Chlorhexidine molecule and iodine in the form of I3- existing for three anion of iodine realize
Space structure is combined closely, and this special chemical structure is obtained, and makes the lasting bactericidal effect and the trip of iodine quick release of Chlorhexidine
It acts on and being effectively combined from iodine quick sterilization, realize the attack synergy to the more target position of pathogen, effectively raise
The bactericidal effect of chlorhexidine iodine disinfectant.It can be used for preparing all kinds of skins, mucous membrane thimerosal, the thimerosal stability prepared
It is good, quick and durable, antibacterial wide spectrum is sterilized, it is small to skin irritation.
The preferred embodiment of the present invention has been described in detail above, but the invention be not limited to it is described
Embodiment, those skilled in the art can also make various equivalent on the premise of not violating the inventive spirit of the present invention
Variation or replacement, these equivalent variation or replacement are all included in the scope defined by the claims of the present application.
Claims (7)
1. preparing a kind of chlorhexidine iodine complexing nano object, which is characterized in that the component and its weight percent of use are as follows:
2. according to claim 1 prepare chlorhexidine iodine complexing nano object, which is characterized in that the Chlorhexidine, iodine
Weight ratio is 1:0.2-5.
3. according to claim 1 prepare chlorhexidine iodine complexing nano object, which is characterized in that the Chlorhexidine is grape
Saccharic acid Chlorhexidine, chlorhexidine acetate.
4. according to claim 1 prepare chlorhexidine iodine complexing nano object, which is characterized in that the surfactant is
Tween-80, poloxamer188 or ethoxylated dodecyl alcohol.
5. according to claim 1 prepare chlorhexidine iodine complexing nano object, which is characterized in that the cosurfactant
N-butanol, n-hexyl alcohol or n-amyl alcohol.
6. according to claim 1 prepare chlorhexidine iodine complexing nano object, which is characterized in that the organic solvent is ring
Hexane, isooctane or n-hexane.
7. chlorhexidine iodine complexing nano object is prepared described in any one of -6 according to claim 1, which is characterized in that including with
Lower step:
(1) iodine, potassium iodide are weighed, dissolution is added water and stirred, 20% iodine solution is made；
(2) Chlorhexidine is weighed, water is added, 20% chlorhexidine is made in stirring and dissolving；
(3) surfactant, cosurfactant are weighed, is added in organic solvent, is stirred and evenly mixed, organic phase is made；
(4) organic phase is divided into two parts.Iodine microemulsion is made in portion plus 20% iodine solution, stirring and emulsifying；Add in another
Chlorhexidine microemulsion is made in 20% chlorhexidine, stirring and emulsifying；
(5) the Chlorhexidine microemulsion is added in iodine microemulsion when being vigorously stirred, continues 40~60min of stirring,
After separating 10min with 40000r.min centrifuge, filtering first uses acetone rinsing, then rinses sediment with purified water；
(6) by sediment be put into vacuum dryer in 70-80 DEG C drying 2-3 hours, obtain the chlorhexidine iodine nanometer
Complex compound.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6203812B1 (en) * | 1998-06-29 | 2001-03-20 | Hydromer, Inc. | Hydrophilic polymer blends used to prevent cow skin infections |
| CN103081940A (en) * | 2013-02-05 | 2013-05-08 | 河南科技学院 | Compound chlorhexidine acetate microemulsion disinfectant and its preparation method |
| WO2013138520A1 (en) * | 2012-03-13 | 2013-09-19 | University Of Tennessee Research Foundation | Composition and system for transdermal delivery |
| CN106581051A (en) * | 2016-11-08 | 2017-04-26 | 太原市诚诚科技有限公司 | Nano microemulsion iodine and preparation method thereof |
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2018
- 2018-09-20 CN CN201811098239.1A patent/CN108969534A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6203812B1 (en) * | 1998-06-29 | 2001-03-20 | Hydromer, Inc. | Hydrophilic polymer blends used to prevent cow skin infections |
| WO2013138520A1 (en) * | 2012-03-13 | 2013-09-19 | University Of Tennessee Research Foundation | Composition and system for transdermal delivery |
| CN103081940A (en) * | 2013-02-05 | 2013-05-08 | 河南科技学院 | Compound chlorhexidine acetate microemulsion disinfectant and its preparation method |
| CN106581051A (en) * | 2016-11-08 | 2017-04-26 | 太原市诚诚科技有限公司 | Nano microemulsion iodine and preparation method thereof |
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