CN104622805A - Econazole nitrate microemulsion and preparation method and application thereof - Google Patents
Econazole nitrate microemulsion and preparation method and application thereof Download PDFInfo
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- CN104622805A CN104622805A CN201510026214.0A CN201510026214A CN104622805A CN 104622805 A CN104622805 A CN 104622805A CN 201510026214 A CN201510026214 A CN 201510026214A CN 104622805 A CN104622805 A CN 104622805A
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Abstract
The invention belongs to the technical field of medicine preparations, particularly relates to an econazole nitrate microemulsion and a preparation method and application thereof, and discloses the econazole nitrate microemulsion. The pharmaceutical composition is prepared from econazole nitrate, a surfactant and a cosurfactant; an oil phase is mixed at a certain ratio; the surfactant is Tween; the cosurfactant is absolute ethyl alcohol; and the oil phase is ethyl butyrate. The econazole nitrate microemulsion disclosed by the invention is simple in prescription, convenient to operate, simple in preparation technology, uniform in particle distribution, small in viscosity, transparent, good in stability and adsorbability, high in bioavailability, long in half-life period, small in side effect of the medicine effect, and controllable in quality; and the product is good in repeatability, and convenient to popularize and utilize.
Description
Technical field
The invention belongs to technical field of medicine, be specifically related to a kind of econazole nitrate microemulsion and preparation method thereof and application.
Background technology
Microemulsion structure by Englishize scholar Sculman and Hoar in nineteen forty-three Late Cambrian.And formally name as microemulsion (microemulsion) in nineteen fifty-nine.Microemulsion structure is the homogeneous system of thermodynamically stable oily water one surfactant one cosurfactant, appearance transparent or similar transparent, also with as Emulsion be equally divided into w/o and o/w type, particle diameter is little, usually between 10-100nm, so be also referred to as microemulsion (Nanoemulsion, NE).This special construction of microemulsion all achieves suitable progress in a lot of field, becomes of surface chemistry important and be very active branch.Micro-emulsion technology has penetrated into the fields such as daily-use chemical industry, fine chemistry industry petrochemical industry, material science, biotechnology and environmental science, research field that become current hot topic in the world, that have huge applications potentiality.Microemulsion also causes the attention of people gradually as the application of pharmaceutical carrier, and microemulsion, as a kind of new drug carrier, has great application potential.Cyclosporin, cancer therapy drug camptothecine, antipyretic and anti-inflammatory medicine indometacin cloth, ibuprofen monooctyl ester micro-emulsion injecta, flurbiprofen injection etc., all have result to show, after microemulsion formulation made by above medicine, dissolubility significantly improves, and bioavailability increases greatly.Microemulsion has larger potentiality and wide prospect as pharmaceutical carrier application, but at the field of Chinese medicines, present research both domestic and external is little, and the product that there is no Chinese medicine micro emulsion comes out, and microemulsion formulation being applied to the field of Chinese medicines is have a extensive future and far reaching work.
Domestic and international research shows, econazole nitrate is broad-spectrum antifungal medicine, sterilization and bacteriostasis effect is all had to dermatophytosis, yeast, diphasic fungi, aspergillosis etc., for the choice drug of the mycotic infection of superficial part diseases such as clinical treatment tinea cruris, tinea manus and pedis, tinea versicolor, monilial dermatitis, but econazole nitrate is when treating fungus attack disease as the disease such as mycete, candidal vaginitis, though curative effect is remarkable, but there is the phenomenon of recurrent exerbation, therefore, how to make that econazole nitrate action time is lasting, therapeutic effect thorough, namely becomes the problem urgently studied.For this reason, the research report of existing various econazole nitrate novel form in recent years, the mucocutaneous release of nanometer microemulsion is the very fast newtype drug medicine-releasing system of developed recently, it can make drug slow disengage, play slow release, controlled-release function, thus it is lasting to reach drug treating time, therapeutic effect is object thoroughly.
Summary of the invention
For this reason, technical problem to be solved by this invention is to provide a kind of microemulsion system being applicable to econazole nitrate system, make it have be evenly distributed, viscosity is little, transparent, good stability excellent adsorption, bioavailability are high, long half time, side effect are little advantage.
For solving the problems of the technologies described above, the invention provides a kind of econazole nitrate microemulsion, this pharmaceutical composition consists of:
The pass of described weight portion and parts by volume is the relation of g/mL.
Further, described econazole nitrate microemulsion, is made up of following component:
Described econazole nitrate microemulsion, wherein, described surfactant is tween.
Arbitrary described econazole nitrate microemulsion, wherein, described cosurfactant is dehydrated alcohol.
Arbitrary described econazole nitrate microemulsion, wherein, described oil phase is ethyl butyrate.
Arbitrary described econazole nitrate microemulsion, wherein, the particle diameter of described microemulsion is 10-100nm.
The invention also discloses the method for arbitrary described econazole nitrate microemulsion, comprise and measure according to selected prescription the step that the mixing of described oil phase, surfactant, cosurfactant and aqueous phase obtains blank microemulsion, and add the econazole nitrate mixing of recipe quantity, to obtain final product.
The invention also discloses the application of arbitrary described econazole nitrate microemulsion in the medicine of preparation treatment monilial dermatitis, eczema, tinea cruris, tinea manus and pedis, tinea versicolor, paronychia, diaper dermatitis, shallow pyoderma.
The invention also discloses arbitrary described econazole nitrate microemulsion selectivity and add customary adjuvant, conveniently the clinical acceptable preparation made of technique.
Described preparation, is characterized in that comprising: spray, foam, a distillate medicinal water.
Microemulsion system of the present invention is based on the characteristic of econazole nitrate, and meticulously screened the microemulsion system being suitable for the most carrying econazole nitrate, not only prescription is simple, easy to operate, preparation technology is simple; And gained microemulsion particles is evenly distributed, viscosity is little, transparent, good stability excellent adsorption, bioavailability are high, long half time; The side effect of drug effect is little, and the favorable reproducibility of quality controllable, product, is convenient to utilization and extention.
Accompanying drawing explanation
In order to make content of the present invention be more likely to be clearly understood, below according to specific experiment example of the present invention, embodiment also by reference to the accompanying drawings, the present invention is further detailed explanation, wherein
Fig. 1 is the blank droplet measurement figure of the blank group of prescription 1 described in experimental example 1 of the present invention;
Fig. 2 is the dosing droplet measurement figure of the dosing group of prescription 1 described in experimental example 1 of the present invention;
Fig. 3 is the blank droplet measurement figure of the blank group of prescription 2 described in experimental example 1 of the present invention;
Fig. 4 is the blank droplet measurement figure of the blank group of prescription 3 described in experimental example 1 of the present invention;
Fig. 5 is the blank droplet measurement figure of the blank group of prescription 4 described in experimental example 1 of the present invention;
Fig. 6 is the dosing droplet measurement figure of the dosing group of prescription 4 described in experimental example 1 of the present invention;
Fig. 7 is the blank droplet measurement figure of the dosing group of prescription 5 described in experimental example 1 of the present invention;
Fig. 8 is the dosing droplet measurement figure of the dosing group of prescription 5 described in experimental example 1 of the present invention;
Fig. 9 is the blank droplet measurement figure of the blank group of prescription 6 described in experimental example 1 of the present invention;
Figure 10 is the dosing droplet measurement figure of the dosing group of prescription 6 described in experimental example 1 of the present invention;
Figure 11 is the blank droplet measurement figure of the blank group of prescription 7 described in experimental example 1 of the present invention;
Figure 12 is the dosing droplet measurement figure of the dosing group of prescription 7 described in experimental example 1 of the present invention;
Figure 13 is the blank droplet measurement figure of the blank group of prescription 8 described in experimental example 1 of the present invention;
Figure 14 is the dosing droplet measurement figure of the dosing group of prescription 8 described in experimental example 1 of the present invention;
Figure 15 is in experimental example 2 of the present invention, as Km=2:1, to the pseudo-ternary phase diagram that described prescription 7 is optimized;
Figure 16 is in experimental example 2 of the present invention, as Km=3:1, to the pseudo-ternary phase diagram that described prescription 7 is optimized;
Figure 17 is in experimental example 2 of the present invention, as Km=4:1, to the pseudo-ternary phase diagram that described prescription 7 is optimized.
Experimental example
The screening of experimental example 1 microemulsion system
1.1 prescriptions 1
Blank group:
Ethyl butyrate 0.5g;
Labraso 3.33g;
Dehydrated alcohol 1.11g;
At room temperature 25 DEG C, mix with 600r/min, above-mentioned adjuvant energy mix homogeneously, and solution is transparent.Namely there is balance-like stricture of vagina after dripping water, become evenly after stirring; Add water 25ml time still clear, stirring of dripping, hairspring scatters evenly, slightly light blue opalescence, electrical conductivity 18.02 μ s/cm, and with 13000r/min high speed centrifugation 10min, solution is not stratified, as seen its stable system.
Dye test: add methylene blue, can disperse rapidly; Add tonyred, disperse slowly and with red particle, prove that described microemulsion system is o/w type microemulsion; To leave standstill after 9 days still clear, evenly free from admixture, short-term stability.Visible, the microemulsion system that said composition is formed is comparatively stable.The particle size distribution detecting this blank microemulsion is shown in Fig. 1.
Dosing group:
Ethyl butyrate 2.0g;
Labraso 13.5g;
Dehydrated alcohol 4.5g;
Room temperature 25 DEG C, 600r/min stir, and gained microemulsion system is transparent but uneven.Drip water and namely can produce a large amount of minute bubbles, electrical conductivity of solution rises by 1.7 μ s/cm; To the 50ml that adds water, system electrical conductivity is maximum, reaches 18.11 μ s/cm; Continue afterwards to add water, electrical conductivity starts to decline; To add water 75ml time, electrical conductivity is 18.09 μ s/cm.The variation characteristic of conductivity value shows the feature that it does not meet O/W type microemulsion.
Get above-mentioned microemulsion system 50g, add crude drug econazole nitrate and dissolve; 500r/min, 25 DEG C of stirrings.Adding 0.3g medicine just has a lot of acicular crystal insoluble.Visible, this microemulsion system is not also suitable for the use of the microemulsion of econazole nitrate.After hold over night, crude drug dissolves.The particle size distribution detecting this dosing microemulsion is shown in Fig. 2.
1.2 prescriptions 2
Blank group
Miglyol 812N 0.5g;
RH-40 (less than 25 DEG C is white solid state) 3.33g;
Dehydrated alcohol 1.11g;
At room temperature 27 DEG C, stir with the speed of 600r/min, gained microemulsion oil phase can be mixed homogeneously with mixed surfactant, and transparent; Then drip water, water enters system, namely can produce balance-like, produces a large amount of bubble in system; Be heated to 35 DEG C and still have a large amount of bubble, the stirring that adds water still has balance-like stricture of vagina, and not adding water, it is transparent to stir; Add water 25ml, electrical conductivity 143.6 μ s/cm.13000r/min high speed centrifugation 10min, gained system is not stratified, and in stable condition; Dye test: add methylene blue, disperses rapidly; Add tonyred, dispersion slowly has red particle, and display proves o/w type microemulsion.To leave standstill after 9 days still clear, homogeneous, a small amount of fluffy solid is arranged at bottom, short-term stability.The particle size distribution detecting this blank microemulsion is shown in Fig. 3.
Dosing group:
Miglyol 812N 2.0g;
RH-40 (less than 25 DEG C is white solid state) 13.5g;
Dehydrated alcohol 4.5g;
At room temperature 25 DEG C, stir with the speed of 600r/min, gained microemulsion system is transparent but uneven.After dripping water, system turns milky white; Along with amount of water increases, system is bleach gradually, and rise to 30.4 DEG C by 24.7 DEG C, the external world does not have thermal source; A large amount of minute bubbles are produced in system; Add water 30ml time, system electrical conductivity is maximum, 197 μ about s/cm; Increase with rate of water added, electrical conductivity is almost constant; Add water 75ml, system electrical conductivity 183.5 μ s/cm, and it is not very transparent that gained system becomes.
Stirring each adjuvant of prescription makes it even, and have a large amount of bubble, temperature raises, T 33 DEG C; Then add water 10ml, electrical conductivity 20 μ s/cm, increases with rate of water added, and electrical conductivity raises.Add water 41ml time, system electrical conductivity 207 μ s/cm; With the increase of rate of water added, system conductivity variations is very little; Add water 50ml again, system electrical conductivity 207 μ s/cm.System has a large amount of minute bubbles, and clear, altogether 67.2g.Get 50g, T 25 DEG C, 500r/min dosing are stirred, and 0.07g just has a lot of insoluble matter; Be heated to 30 DEG C, 0.10g just has a lot of acicular crystal and sheet-shaped material medicine.Except bulky grain medicine after hold over night, almost all dissolve.
1.3 prescriptions 3
Blank group:
Oleum Ricini 0.5g;
RH-40 3.33g；
Dehydrated alcohol 1.11g;
At the temperature of 35 DEG C, stir with the rotating speed of 600r/min, gained microemulsion system oil phase can be mixed homogeneously with mixed surfactant, and transparent; After dripping water, system has balance-like stricture of vagina, produces a lot of minute bubbles; Add water 16.5ml time electrical conductivity maximum, 169.7 μ s/cm; Add water 25ml time system electrical conductivity 139.1 μ s/cm, the homogeneous band opalescence of system, jolting produces a large amount of bubble.Through 13000r/min high speed centrifugation 10min, system is not stratified, and in stable condition;
Dye test: after adding methylene blue, system is disperseed rapidly; Add tonyred, system dispersion slowly has red particle, therefore proves that this system is o/w type microemulsion; After hold over night, system still clarifies non-layering; Leave standstill after 8 days, system still clear is homogeneous, the non-layering of free from admixture, short-term stability.The blank droplet measurement figure of blank group is specifically shown in Fig. 5.
Dosing group:
Oleum Ricini 2.0g;
RH-40 13.5g；
Dehydrated alcohol 4.5g;
Above mixed system is stirred, after dripping water with the speed of 600r/min; Gained microemulsion system produces a large amount of bubble, T32.3 DEG C; Add water 43ml time, system electrical conductivity 207 μ s/cm; When add water 46ml time, system electrical conductivity 210 μ s/cm; Increase with rate of water added afterwards, system electrical conductivity declines; Add water again 60ml time, system electrical conductivity 205 μ s/cm.System is not very transparent, and slightly suppurative mastitis is yellow.
Stirring system self defocusing heat, system produces a large amount of bubble; Add water 45ml time system electrical conductivity be 210 μ s/cm to the maximum; Add water 50ml time system electrical conductivity 204 μ s/cm.System clear.
System is 69.47g altogether, and get 50g and add crude drug, at room temperature 25 DEG C, stir with the speed of 500r/min, adding 0.10g medicine just has the visible insoluble crystal of a large amount of naked eyes; After hold over night, crude drug almost all dissolves.
1.4 prescriptions 4
Blank group:
Ethyl butyrate 0.5g;
RH-40 3.33g；
Dehydrated alcohol 1.11g;
After at the temperature of 40 DEG C, the speed of 600r/min stirs, the oil phase of gained microemulsion system mixes rear system clear homogeneous with mixed surfactant; After dripping water, there is balance-like stricture of vagina in system and produce a large amount of bubble; The 25ml system that adds water electrical conductivity 171.5 μ s/cm, system clear; Then with 13000r/min high speed centrifugation 10min, this system is not stratified, and in stable condition; After hold over night, system still clarifies non-layering; Leave standstill after 8 days, system still clear is homogeneous, the non-layering of free from admixture, short-term stability.The blank droplet measurement figure of blank group is specifically shown in Fig. 7.
Dosing group:
Ethyl butyrate 2.0g;
RH-40 13.5g；
Dehydrated alcohol 4.5g;
At the temperature of 25 DEG C, stir with the speed of 600r/min; After dripping water, the microemulsion system electrical conductivity of gained raises, and produce a large amount of bubble, system heat release, temperature is increased to about 31 DEG C; Add water 45ml time, system electrical conductivity is the highest, 191.5 μ s/cm; Add water, system electrical conductivity declines gradually again, add water 50ml time, system electrical conductivity 193.1 μ s/cm.Get microemulsion system 50g, at the temperature of 25 DEG C, stir with the speed dosing of 500r/min, adding 0.26g crude drug just has the visible insoluble matter of naked eyes.The dosing droplet measurement figure of dosing group is shown in Fig. 8.
1.5 prescriptions 5
Blank group:
Oleic acid polyethyleneglycol glyceride 0.5g;
RH-40 3.33g；
Dehydrated alcohol 1.11g;
At the temperature of 30 DEG C, stir with the speed of 600r/min; After the microemulsion system oil phase of gained mixes with mixed surfactant, system is transparent, thickness, and after stirring, system has balance-like stricture of vagina; Drip water and produce a large amount of minute bubbles; Add water 16.2ml time, the maximum 196.9 μ s/cm of system electrical conductivity; Add water 25ml time, system electrical conductivity 167.9 μ s/cm, the transparent slightly opalescence of system; Then with 13000r/min high speed centrifugation 10min, gained microemulsion system is not stratified, and stable; After hold over night, system still clarifies non-layering; Leave standstill after 8 days, system still clear is homogeneous, the non-layering of free from admixture, short-term stability.The blank droplet measurement figure of blank group is specifically shown in Fig. 9.
Dosing group
Oleic acid polyethyleneglycol glyceride 2.0g;
RH-40 13.5g；
Dehydrated alcohol 4.5g;
At the temperature of 25 DEG C, stir with the speed of 600r/min, the microemulsion system of gained is not very transparently show slightly yellow, electrical conductivity 19.8 μ s/cm; Then drip water, after being added to about 5ml, system becomes sticky thick, gel, and system is dispelled the heat, and when temperature is about 32 DEG C, has a large amount of bubble to produce; Add water 41ml time system electrical conductivity maximum, 199.4 μ s/cm; Add water 50ml time, system electrical conductivity 197.3 μ s/cm, system is transparent homogeneous, and slightly general opalescence.Get microemulsion system 50g, at the temperature of 25 DEG C, stir with the speed dosing of 500r/min, adding 0.15g crude drug just has the visible insoluble matter of naked eyes.The dosing droplet measurement figure of dosing group is shown in Figure 10.
1.6 prescriptions 6
Blank group
Ethyl oleate 0.5g;
Tween 80 3.33g;
Dehydrated alcohol 1.11g;
At the temperature of 25 DEG C, stir with the speed of 600r/min, the microemulsion oil phase of gained mixes rear system yellow transparent with mixed surfactant, have balance-like stricture of vagina during stirring; Drip water and produce a large amount of minute bubbles; Add water 8ml time, system electrical conductivity 80 μ s/cm, along with the increase system of amount of water electrical conductivity continue increase; Add water 16ml time system electrical conductivity maximum, 147.1 μ s/cm; Add water 25ml time, system is transparent homogeneous, slightly yellow, electrical conductivity 126.5 μ s/cm; Concussion can produce a lot of minute bubbles, and after leaving standstill, system is transparent homogeneous.Then with 13000r/min high speed centrifugation 10min, gained system is not stratified, and stable; After hold over night, system still clarifies non-layering; Leave standstill after 8 days, system still clear is homogeneous, the non-layering of free from admixture, short-term stability.The blank droplet measurement figure of blank group is shown in Figure 11.
Dosing group
Ethyl oleate 2.0g;
Tween 80 13.5g;
Dehydrated alcohol 4.5g;
At the temperature of 25 DEG C, stir with the speed of 600r/min, the microemulsion system yellow transparent of gained; Drip water, add about 10ml, system becomes sticky thick, and presents gel, and system is dispelled the heat, and is about 32 DEG C, has a large amount of bubble to produce in temperature; Add water 31ml time system electrical conductivity maximum, 148.6 μ s/cm; Add water 50ml time, system electrical conductivity 145.6 μ s/cm, system is faint yellow, clear.
Get microemulsion system 50g, at temperature 28 DEG C, carry out dosing stirring with the speed of 500r/min, adding 0.11g crude drug just has the visible insoluble matter of naked eyes.The dosing droplet measurement figure of dosing group is shown in Figure 12.
1.7 prescriptions 7
Blank group
Ethyl butyrate 0.5g;
Tween 80 3.33g;
Dehydrated alcohol 1.11g;
At the temperature of 25 DEG C, stir with the speed of 600r/min, the oil phase of gained system mixes rear system yellow transparent with mixed surfactant, have balance-like stricture of vagina during stirring; Drip water and produce a large amount of minute bubbles, system has balance-like stricture of vagina; Add water 14.5ml time system electrical conductivity maximum 142.7 μ s/cm; The 25ml system that adds water is transparent homogeneous, and color slightly presents yellow, electrical conductivity 121.9 μ s/cm, and jolting produces a large amount of minute bubbles; With 13000r/min high speed centrifugation 10min, system generation layering, there is very thin one deck oil on centrifuge tube upper strata, and leaving standstill and observe, also may be that mixed system surface tension is little, and in centrifuge tube, liquid level concave arc degree is large, side observe phenomena with have the thin oil phase of one deck seemingly; Leave standstill after 8 days, phenomenon, with the same during preparation, does not have obvious layering; A small amount of fluffy solid is arranged at bottom.The blank droplet measurement figure of blank group is shown in Figure 13.
Dosing group
Ethyl butyrate 2.0g;
Tween 80 13.5g;
Dehydrated alcohol 4.5g;
At the temperature of 21 DEG C, stir with the speed of 600r/min, the microemulsion system yellow transparent of gained; Drip water, system heat release, temperature is increased to 26.2 DEG C, and electrical conductivity raises, and has been attended by the generation of a large amount of bubble; Add water 45ml time system electrical conductivity maximum, 144.8 μ s/cm; Add water 50ml time, system electrical conductivity 144.7 μ s/cm, system is faint yellow and color is transparent.
Get microemulsion system 50g, at the temperature of 28 DEG C, carry out dosing stirring with the speed of 500r/min, adding 0.20g crude drug just has the visible insoluble matter of naked eyes.The dosing droplet measurement figure of dosing group is shown in Figure 14.
1.8 prescriptions 8
Blank group
Ethyl butyrate 0.5g;
Polysorbas20 3.33g;
Dehydrated alcohol 1.11g;
At the temperature of 25 DEG C, stir with the speed of 600r/min, after the oil phase of the microemulsion system of gained mixes with mixed surfactant, system is transparent but uneven, has balance-like stricture of vagina during stirring; Drip water and produce a large amount of minute bubbles, the increase system electrical conductivity with rate of water added increases; The 20ml that adds water is that system electrical conductivity is maximum, 210 μ s/cm; Add water 25ml time, system electrical conductivity is 209 μ s/cm, and system homogeneous transparent, produces a large amount of bubble during jolting; Then with 13000r/min high speed centrifugation 10min, gained microemulsion system is not stratified, stable; After hold over night, system still clarifies non-layering; Leave standstill after 7 days, system still clear is homogeneous, non-layering, and a small amount of fluffy solid is arranged at bottom; Short-term stability.The blank droplet measurement figure of blank group is shown in Figure 15.
Dosing group
Ethyl butyrate 2.0g;
Polysorbas20 13.5g;
Dehydrated alcohol 4.5g;
At the temperature of 20.8 DEG C, stir with the speed of 600r/min, the microemulsion system of gained is transparent; After dripping water, system starts heat release, and temperature is increased to 27.6 DEG C, and electrical conductivity raises; Add water 75ml, and system electrical conductivity continues to raise.Add water about 50ml time, system electrical conductivity raises slowly; Add water again 83ml time, system electrical conductivity 228 μ s/cm; When continuing to add water 93ml, system electrical conductivity 229 μ s/cm
System amount of water is more, gets microemulsion system 50g, at the temperature of 25 DEG C, stirs with the speed dosing of 600r/min, and adding 0.10g crude drug just has the visible insoluble matter of naked eyes.The dosing droplet measurement figure of dosing group is shown in Figure 16.
As known in above-mentioned experimental result: after prescription 4 places 4 days blank keep sample with dosing all become milky white opaque, but the sample of the prescription 4 stayed time screening in early stage (amount is few) is still clear.Prescription 2 also shows slightly milky white, and keeping sample of lab scale is still clear before.By the particle size distribution overall merit of the outward appearance for microemulsion system, the dissolubility to econazole nitrate, microemulsion, the effect of prescription 7 is the most suitable, is preferred plan.
Experimental example 2 formulation optimization:
2.1 amplify prescription 7, and dosing 1% is for bacteriostatic test:
System cumulative volume 520ml, total dose 5.12g; Wherein ethyl butyrate 15.0g, Tween 80 100g, dehydrated alcohol 33.3g.
2.2 amplify prescription 7, and dosing 0.5% is for bacteriostatic test:
System gross weight 418.79g, total dose 2.1g; Wherein ethyl butyrate 12.12g, Tween 80 80.78g, dehydrated alcohol 26.90g.
2.3 amplify prescription 7 stays 100ml as blank.
2.4 utilize pseudo-ternary phase diagram to be optimized prescription 7:
(1) proportioning of Km=2:1 each phase adjuvant is as shown in table 1:
The proportioning of each adjuvant of table 1
When Km=2:1, corresponding pseudo-ternary phase diagram is shown in Figure 15.
(2) proportioning of Km=3:1 each phase adjuvant is as shown in table 2:
The proportioning of each adjuvant of table 2
When Km=3:1, corresponding pseudo-ternary phase diagram is shown in Figure 16.
(3) proportioning of Km=1:1 each phase adjuvant is as shown in table 3:
The proportioning of each adjuvant of table 3
(4) proportioning of Km=4:1 each phase adjuvant is as shown in table 4:
The proportioning of each adjuvant of table 4
When Km=4:1, corresponding pseudo-ternary phase diagram is shown in Figure 17.
Can be found out by above pseudo-ternary phase diagram, when Km value is 3 ~ 4 time, oil phase can be mixed to form microemulsion system with more aqueous phase.
The contrast experiment of experimental example 3 fungistatic effect
One, equipment:
1. test strain: Candida albicans ATCC12301 is provided by China General Microbiological culture presevation administrative center, test uses the fresh slant culture of 24h.
2. antibacterial name of product: contrast medicine (0.3%), contrast medicine (0.5%), contrast medicine (0.8%), microemulsion (0.3%), microemulsion (0.8%).The contrast medicine of this experimental example of < is by formula preparation > described in embodiment 1
3. diluent .0.03mol/L phosphate buffer (PBS).
Two, method:
1. test basis: " disinfection technology standard " (version in 2002) 2.1.11.
2. testing conditions: test temperature 22 DEG C, relative humidity 50%.
3. press down Seedling test; Fresh for test organisms 24h slant culture PBS is washed down, makes 5x10
5cfu/ml ~ 5x10
6the Seedling suspension of cfu/ml.Get by test liquid and contrast sample liquid 5mL respectively, be placed in (standby 4 pipes) in sterile test tube, get above-mentioned bacteria suspension and dripped 0.1mL. mixing by test liquid with contrasting in sample liquid each respectively, start timing, effect 2,5,10, after 20min, drawing sample liquid 0.5mL respectively drops into containing 5mL PBS in vitro, abundant mixing, do suitable dilution, then get 20 dilution factors wherein, draw 0.5mL respectively, be inoculated in nutrient agar with tilt-pour process, cultivate 48h for 37 DEG C, do live vaccine and fall to counting, test repetition 3 times.
Three, result: the fungistatic effect of each group is as shown in table 5,6,7,8,9:
Table 5 contrasts medicine (0.3%) to the fungistatic effect of Candida albicans
Note: the concentration of test bacteria suspension is 4.8*106cfu/mL (3.9*106cfu/mL ~ 5.7*106cfu/mL)
Table 6 contrasts medicine (0.5%) to the fungistatic effect of Candida albicans
Note: the concentration of test bacteria suspension is 4.8*106cfu/mL (3.9*106cfu/mL ~ 5.7*106cfu/mL)
Table 7 contrasts medicine (0.8%) to the fungistatic effect of Candida albicans
Note: the concentration of test bacteria suspension is 4.8*106cfu/mL (3.9*106cfu/mL ~ 5.7*106cfu/mL)
Table 8 microemulsion (0.3%) is to the fungistatic effect of Candida albicans
Note: the concentration of test bacteria suspension is 4.8*106cfu/mL (3.9*106cfu/mL ~ 5.7*106cfu/mL)
Table 9 microemulsion (0.8%) is to the fungistatic effect of Candida albicans
Note: the concentration of test bacteria suspension is 4.8*106cfu/mL (3.9*106cfu/mL ~ 5.7*106cfu/mL)
Four, conclusion
Show through three repeated trials, contrast medicine (0.3%), to Candida albicans effect 20min bacteriostasis rate >50%, shows that this product has more weak bacteriostasis to Candida albicans; Contrast medicine (0.5%) is to Candida albicans effect 10min bacteriostasis rate >50%, show that this product has Candida albicans Seedling and press down Seedling effect: contrast medicine (0.8%), to Candida albicans effect 10min bacteriostasis rate >90%, shows that this product has stronger bacteriostasis to Candida albicans; To Candida albicans effect 20min bacteriostasis rate >50%-, microemulsion (0.3%) shows that this product has more weak bacteriostasis to Candida albicans; Microemulsion (0.8%), to Candida albicans effect 1 0mm bacteriostasis rate >90%, shows that this product has Candida albicans Seedling and stronger presses down Seedling effect.
Embodiment
Embodiment 1
Econazole nitrate microemulsion described in the present embodiment is made up of following component:
Described in the present embodiment, econazole nitrate microemulsion is prepared as follows: measure according to selected prescription the step that the mixing of described oil phase, surfactant, cosurfactant and aqueous phase obtains blank microemulsion, and add the econazole nitrate mixing of recipe quantity, to obtain final product.
Embodiment 2
Econazole nitrate microemulsion described in the present embodiment is made up of following component:
Described in the present embodiment, econazole nitrate microemulsion is prepared as follows: measure according to selected prescription the step that the mixing of described oil phase, surfactant, cosurfactant and aqueous phase obtains blank microemulsion, and add the econazole nitrate mixing of recipe quantity, to obtain final product.
Embodiment 3
Econazole nitrate microemulsion described in the present embodiment is made up of following component:
Described in the present embodiment, econazole nitrate microemulsion is prepared as follows: measure according to selected prescription the step that the mixing of described oil phase, surfactant, cosurfactant and aqueous phase obtains blank microemulsion, and add the econazole nitrate mixing of recipe quantity, to obtain final product.
Embodiment 4
Econazole nitrate microemulsion described in the present embodiment is made up of following component:
Described in the present embodiment, econazole nitrate microemulsion is prepared as follows: measure according to selected prescription the step that the mixing of described oil phase, surfactant, cosurfactant and aqueous phase obtains blank microemulsion, and add the econazole nitrate mixing of recipe quantity, to obtain final product.Embodiment 5
Econazole nitrate microemulsion described in the present embodiment is made up of following component:
Described in the present embodiment, econazole nitrate microemulsion is prepared as follows: measure according to selected prescription the step that the mixing of described oil phase, surfactant, cosurfactant and aqueous phase obtains blank microemulsion, and add the econazole nitrate mixing of recipe quantity, to obtain final product.
Embodiment 6
Econazole nitrate microemulsion described in the present embodiment is made up of following component:
Described in the present embodiment, econazole nitrate microemulsion is prepared as follows: measure according to selected prescription the step that the mixing of described oil phase, surfactant, cosurfactant and aqueous phase obtains blank microemulsion, and add the econazole nitrate mixing of recipe quantity, to obtain final product.
Embodiment 7
Econazole nitrate microemulsion described in the present embodiment is made up of following component:
Described in the present embodiment, econazole nitrate microemulsion is prepared as follows: measure according to selected prescription the step that the mixing of described oil phase, surfactant, cosurfactant and aqueous phase obtains blank microemulsion, and add the econazole nitrate mixing of recipe quantity, to obtain final product.
Obviously, above-described embodiment is only for clearly example being described, and the restriction not to embodiment.For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description.Here exhaustive without the need to also giving all embodiments.And thus the apparent change of extending out or variation be still among the protection domain of the invention.
Claims (10)
1. an econazole nitrate microemulsion, is characterized in that, is made up of following component:
The pass of described weight portion and parts by volume is the relation of g/mL.
2. econazole nitrate microemulsion as claimed in claim 1, is characterized in that, be made up of following component:
3. econazole nitrate microemulsion as claimed in claim 1 or 2, is characterized in that:
Described surfactant is tween.
4. the econazole nitrate microemulsion as described in as arbitrary in claim 1-3, is characterized in that:
Described cosurfactant is dehydrated alcohol.
5. the econazole nitrate microemulsion as described in as arbitrary in claim 1-3, is characterized in that:
Described oil phase is ethyl butyrate.
6. the econazole nitrate microemulsion as described in as arbitrary in claim 1-5, it is characterized in that, the particle diameter of described microemulsion is 10-100nm.
7. prepare the method for the arbitrary described econazole nitrate microemulsion of claim 1-6 for one kind, it is characterized in that, comprise and measure according to selected prescription the step that the mixing of described oil phase, surfactant, cosurfactant and aqueous phase obtains blank microemulsion, and add the econazole nitrate mixing of recipe quantity, to obtain final product.
8. the application of the econazole nitrate microemulsion as described in as arbitrary in claim 1-6 in the medicine of preparation treatment monilial dermatitis, eczema, tinea cruris, tinea manus and pedis, tinea versicolor, paronychia, diaper dermatitis, shallow pyoderma.
9. the arbitrary described econazole nitrate microemulsion selectivity of claim 1-6 adds customary adjuvant, conveniently the clinical acceptable preparation made of technique.
10. preparation as claimed in claim 9, is characterized in that comprising: spray, foam, a distillate medicinal water.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109350599A (en) * | 2018-12-12 | 2019-02-19 | 辽宁新高制药有限公司 | A kind of spray for the treatment of skin oidiomycosis |
| CN110613684A (en) * | 2019-10-16 | 2019-12-27 | 李丽丽 | Posaconazole nanoemulsion and preparation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2609714A1 (en) * | 1987-01-15 | 1988-07-22 | Sanofi Sa | Stable liquid compositions based on fungicidal imidazole derivatives |
| CN1931165A (en) * | 2006-09-21 | 2007-03-21 | 西北农林科技大学 | Nanometer antifungal econazole nitrate emulsion medicine and its prepn process |
| CN1931163A (en) * | 2006-09-20 | 2007-03-21 | 西北农林科技大学 | Nanometer clotrimazole emulsion medicine and its prepn process |
| CN101518514A (en) * | 2009-04-08 | 2009-09-02 | 周小萍 | Econazole nitrate microemulsion aerosol and method for preparing same |
| CN104208656A (en) * | 2014-09-10 | 2014-12-17 | 河南牧翔动物药业有限公司 | Virginiamycin microemulsion and preparation method thereof |
-
2015
- 2015-01-19 CN CN201510026214.0A patent/CN104622805B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2609714A1 (en) * | 1987-01-15 | 1988-07-22 | Sanofi Sa | Stable liquid compositions based on fungicidal imidazole derivatives |
| CN1931163A (en) * | 2006-09-20 | 2007-03-21 | 西北农林科技大学 | Nanometer clotrimazole emulsion medicine and its prepn process |
| CN1931165A (en) * | 2006-09-21 | 2007-03-21 | 西北农林科技大学 | Nanometer antifungal econazole nitrate emulsion medicine and its prepn process |
| CN101518514A (en) * | 2009-04-08 | 2009-09-02 | 周小萍 | Econazole nitrate microemulsion aerosol and method for preparing same |
| CN104208656A (en) * | 2014-09-10 | 2014-12-17 | 河南牧翔动物药业有限公司 | Virginiamycin microemulsion and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 周静等: "硝酸益康唑纳米乳滴眼剂的制备及理化性质研究", 《中国医院药学杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109350599A (en) * | 2018-12-12 | 2019-02-19 | 辽宁新高制药有限公司 | A kind of spray for the treatment of skin oidiomycosis |
| CN110613684A (en) * | 2019-10-16 | 2019-12-27 | 李丽丽 | Posaconazole nanoemulsion and preparation method thereof |
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|---|---|
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