CN104146957A - Submicroemulsion antifungal drug spray preparation - Google Patents
Submicroemulsion antifungal drug spray preparation Download PDFInfo
- Publication number
- CN104146957A CN104146957A CN201410356128.1A CN201410356128A CN104146957A CN 104146957 A CN104146957 A CN 104146957A CN 201410356128 A CN201410356128 A CN 201410356128A CN 104146957 A CN104146957 A CN 104146957A
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- Prior art keywords
- oil
- oleum
- submicron emulsion
- antifungal
- drug
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a submicroemulsion antifungal drug spray preparation. The preparation mainly comprises the following components: an antifungal chemical synthetic drug, lecithin serving as an emulsifier, a transdermal absorption penetration enhancer and a skin protectant, soybean oil or other essential oils serving as an oil soluble diluent, glycerin serving as an isoosmotic adjusting agent, oleic acid serving as a co-emulsifier and a transdermal absorption penetration enhancer, azone serving as a transdermal absorption penetration enhancer, vitamin E serving as an antioxidant and a skin protectant, ethyl alcohol serving as a transdermal absorption penetration enhancer, natural essential oil serving as a transdermal absorption penetration enhancer, an antibacterial natural drug and essence. The submicroemulsion antifungal drug spray preparation has the advantages that the solubility and the uniformity of oil soluble antifungal drugs in water are increased, the transdermal absorption of the drugs is enhanced, the drugs are fed into dermis, and the absorption and utilization ratios of the drugs are increased, so that the effects of the antifungal drugs are increased; in the meantime, a cosolvent with side effects is avoided from being used, so that toxic and side effects caused by drugs entering whole body blood circulation systems and the stimulation to the skin are reduced, and the efficacies of protecting the skin and improving the looks are provided.
Description
Technical field
The invention belongs to field of medicaments, relate to antifungal agent composition spray preparation, particularly submicron emulsion antifungal agent composition spray preparation.
Background technology
Beriberi, has another name called tinea pedis.The traditional Chinese medical science think primary disease taking sufficient chamber numbness, ache, weakness is as primary symptom.According to its Symptoms, be mainly divided into dry beriberi, beriberi caused by pathogenic damp and cardiac beriberi etc.From the beginning of time, dizzy weak, tired anorexia, there is the sense of creeping of prickling sensation or Formica fusca in foot, be ankle socks type and distribute, muscular soreness then, muscular strength goes down, dermal sensation is blunt, muscle arteries and veins speeds to open, contractura, foot edema.There is cardiopalmus, breathe hard in severe patient, tachycardia, and cardiac dilatation, lower limb swell and ache, when the knee joint that swelled and ache is to thigh portion, obnubilation, the vomiting of panting, is the shape of being critically ill, and needs first aid.Sui's Chao Yuanfang (550-630 A.D.) " General Treatise on the Cause and Symptoms of Diseases " has been done careful discussion to primary disease.On western medicine, being called sufficient addiction, is a kind of very common, multiple, chronic, infectious dermatosis, is to be caused by superficial part pathomycete.The morbidity fungus of common infringement human body skin has trichophyton, trichophyton gypseum, acrothesium floccosum and Candida albicans etc. more than 20 to plant
[1].
The reason of beriberi morbidity mainly contains following points: 1), skin of sole of foot do not have sebaceous gland, lack can Antifungi fatty acid; 2), the condition of applicable conk breeding is that relative humidity is that 80%-95%, temperature are the alkaline environment of 25 DEG C-30 DEG C.In toe space and the hyperhidrosis of foot bottom, local alkaline environment provide good condition for conk breeding; 3), skin of sole of foot horny layer is thicker, the keratoprotein in horny layer provides abundant nutrient for conk.So every summer and autumn, beriberi prevalence increases, and adds seldom foot bath or often wears airtight footgear, just more easily suffers from " beriberi " or " beriberi " increased the weight of." beriberi " looks it is minor illness, but sometimes very itches and affect study and work, and secondary infection can serious harm health, can self infect simultaneously and causes and the tinea manuum, tinea corporis and tinea unguium even also can infect other people.
Beriberi has had a strong impact on people's quality of life, and an investigation of department of dermatologry association of Chinese Medical Association shows, in the Dermatology Outpatient Department of various big hospital, in medical patient, nearly half suffers from beriberi.Especially fungus-caused beriberi also can increase with the increase at age, suffers from the ratio of beriberi up to 3/4 in adult.In addition, male's sickness rate is also higher than women.In the whole nation such as Beijing, Shanghai, 300 investigation that hospital carries out show that the prevalence of beriberi, tinea unguium exceeds doctor's expectation (up to 30-70%)
[2].The people of old people, overweight people, diabetes patient, often swimming is this group of people at high risk who is medically called as tinea unguium, it is estimated that the whole nation has patient several ten million people at least.Owing to thinking little of " beriberi " sick treatment, cause that other local patients that infect of the healths such as secondary infection, the tinea manuum, tinea cruris, tinea corporis have accounted for more than 33%, and easily cross infection, bring more trouble.Therefore must take seriously.
Conventionally beriberi is divided into three types clinically: erosive type, vesicle, keratinization type.1), dipping erosive type: be apt to occur between the 3rd and the 4th, the 4th and the 5th toe.From the beginning of moist between toe, horny layer floods, turns white, soft, exposes red rotten to the corn face or honeycomb substrate after stripping off, and can have a little sepage, very itch, and this kind of easy secondary infection, complicated with acute lymphangitis, erysipelas; 2), squama vesicle: be everlasting between toe, at the bottom of the sole of the foot and lateral margin repeatedly there is the large hillock man of virtue and ability of syringe needle and a trace man of virtue and ability, assemble or be dispersed in, there are inflammatory reaction and Pruritus in various degree, desquamation after trace is dry, is little eckband shape or large stretch of shape, constantly comes off, constantly occur, sometimes only show as master with desquamation, very itch, after scratching often because secondary infection causes erysipelas, lymphangitis etc.; 3), keratinization type: be apt to occur in heel.The palm sole of the foot obvious keratinization, pachyderma, coarse have a desquamation, and pruritus, easily chaps.This type is without washmarking and suppuration, and the course of disease is slow, does not heal for many years.The type of general morbidity summer and autumn is mainly taking vesicle and erosive type as main.
Beriberi patient should and early treatment.Treatment beriberi is generally used external antifungal chemical synthetic drug or Chinese medicine.Clinical can be according to three of beriberi kind of dissimilar treatment.In the time there is the symptom of decortication, breach in patient's foot, belong to keratinization drying type, for this type of patient, medication should be taking cream, unguentum as main; If the patient of vesicle erosive type, i.e. affected part infiltration, just can not image angle drying type patient such to this class patient, use zest to cross by force or the medicine such as ointment, and should first affected part be processed more dryly, and then treat with medicine powder; Also have a class patient to belong to the type of interleaving, the position having is dried, decortication, and rotten flowing water is wasted at some positions, now just medication as the case may be.Except distinguishing type medication, patient also should pedicure journey medication under doctor's guidance.There are two hang-ups in treating beri-beri field, the one, beriberi protracted course of disease, often recurrence, the 2nd, existing treatment is long the course for the treatment of, causes patient compliance poor, affects therapeutic effect.Because the extremely difficult radical cure of beriberi, especially Heal Thyself is usually made a futile effort, so all can have new beriberi medicament to appear on the market every year.But some Therapeutic Method and medicine irritation are larger, can cause anaphylaxis.Can make affected part occur the red and swollen even symptom of flowing water, cause aggravation.
The dermatosis such as tinea pedis are positioned at the epidermal tissue that hair follicle, sebaceous gland etc. are lived mostly, and the successful key of clinical treatment is that medicine must see through horny layer and reach diseased region, and maintain enough drug level at pathological changes point and reach the regular hour.But the beriberi majority of clinical current use can not see through keratodermatitis and reach diseased region, so can not eradicate sufferer.
Submicron emulsion is taking vegetable oil (main component is as fatty acid triglycercide) as oil phase, is aided with oil-in-water type (O/W) Emulsion that phospholipid emulsifier, isotonic agent and water for injection emulsifying make
[3].Submicron emulsion preparation utilizes emulsifying technology that medicine is dispersed in microemulsion, and its Main Components comprises refined soybean oil or other refined oils, lecithin and glycerol.Their effect is respectively oil-soluble diluent, emulsifying agent and isoosmotic adjusting agent.Refined soybean oil, lecithin and glycerol are all natural products, nontoxic, have no side effect.
The particle diameter of submicron emulsion is little and be evenly distributed, and good stability, has certain targeting, can obviously reduce the toxic and side effects of medicine, reduces the zest of medicine, improves the bioavailability of medicine, has become the important preparation research direction that improves curative effect of medication
[4].Therefore, in recent years submicron emulsion by extensive concern.Topical, as a very important part wherein, has also caused people's interest.Submicron emulsion plays treatment and protective effect to wound or affected skin, mucosa; both be conducive to medicine and contacted with affected part, and in part performance drug effect, can avoid again producing untoward reaction because of systemic Absorption; there is effect of skin protection, beauty treatment simultaneously, upgraded route of administration and skin protection idea.Meanwhile, submicron emulsion itself is biodegradable, and avirulence does not produce skin irritation, is the comparatively ideal dosage form of local skin medication.
Can solve dissolubility and the homogeneity of oil-soluble antifungal drug in water by preparing submicron emulsion; can strengthen the Transdermal absorption of medicine and medicine be sent into skin corium and improve the degree of absorbing of medicine; avoid the cosolvent with side effect to use; enter the caused toxic and side effects of systemic blood blood circulation and the stimulation to skin to reduce medicine, and there is effect of protection skin and beauty treatment.
Summary of the invention
Submicron emulsion antifungal agent composition spray preparation of the present invention; be intended to utilize submicron emulsion to pass the complementary action of medicine technology, antioxidant, Derma-Guard and polynary compound percutaneous absorption transdermal enhancers; increase the dissolubility of medicine and the permeability to keratodermatitis, play the effect of sterilizing skin-protective.Submicron emulsion preparation has well solved the water solublity of medicine; strengthen the Transdermal absorption of medicine and medicine sent into skin corium and improve the fragmentation effect of medicine to various pathogenic bacterias including fungus; significantly must improve drug effect; strengthen drug treating time; avoided the use of the traditional cosolvent that has side effect simultaneously; can reduce medicine and cosolvent and enter systemic blood blood circulation, not only reduce the stimulation to skin, also skin be had to good protective effect.
Realizing the technical solution used in the present invention is, submicron emulsion antifungal agent composition spray preparation, and active component comprises: 1) antifungal chemical synthetic drug; 2) as the lecithin of emulsifying agent, percutaneous absorption transdermal enhancers and Derma-Guard; 3) as soybean oil or other quintessence oils of oil-soluble diluent; 4) as the glycerol of isoosmotic adjusting agent; 5) as the oleic acid of co-emulsifier, percutaneous absorption transdermal enhancers; 6) as the azone of percutaneous absorption transdermal enhancers; 7) as the vitamin E of antioxidant and Derma-Guard; 8) as the ethanol of percutaneous absorption transdermal enhancers; 9) as the natural essential oil of percutaneous absorption transdermal enhancers, antimicrobial natural medicine and essence;
Be 0.005-1.2% (w/v) as the consumption of antifungal chemical synthetic drug;
Consumption as the lecithin of emulsifying agent, percutaneous absorption transdermal enhancers and Derma-Guard is 9.27-9.94% (w/v);
Be 0.5-5% (w/v) as the soybean oil of oil-soluble diluent or the consumption of other quintessence oils;
Consumption as the glycerol of isoosmotic adjusting agent is 2.2% (w/v);
Consumption as the oleic acid of co-emulsifier and percutaneous absorption transdermal enhancers is 0-0.45% (w/v);
Be 0-0.01% (w/v) as the consumption of percutaneous absorption transdermal enhancers azone;
Consumption as the vitamin E of antioxidant and Derma-Guard is 0-0.03% (w/v);
Consumption as the natural essential oil of percutaneous absorption transdermal enhancers, antimicrobial natural medicine and essence is 0-0.6% (w/v);
As the ethanol 10-20% of percutaneous absorption transdermal enhancers;
Surplus is water.
By whole submicron emulsion antifungal agent composition spray preparations of preparing of above-claimed cpd.
Saidly as antifungal drug be: one or more in miconazole, triaconazole, ECONAZOLE, ketoconazole, itraconazole, econazole, fluconazol, fenticonazole, sulconazole, tioconazole, Sertaconazole, terconazole (triaconazole), croconazole, isoconazole, fluorine triaconazole and their salt compound.
The said lecithin as emulsifying agent, percutaneous absorption transdermal enhancers and Derma-Guard can be: one or more in Ovum Gallus domesticus Flavus lecithin, soybean lecithin, hydrogenated yolk lecithin, hydrogenated soy phosphatidyl choline, synthetic lecithin, sphingomyelins.
The said soybean oil as oil-soluble diluent or other quintessence oils can be: any in refined soybean oil, refined maize oil, refining Oleum Helianthi, refining Oleum Arachidis hypogaeae semen, refining Oleum sesami, refining Oleum Brassicae campestris.
Said as percutaneous absorption transdermal enhancers, the natural essential oil of antimicrobial natural medicine and essence can be: Oleum Curcumae, Oleum Bulbus Allii, Rhizoma Chuanxiong oil, Herba Artemisiae Annuae oil, Oleum Hippophae, wintergreen oil, Radix Oenotherae erythrosepalae pool, Radix Angelicae Sinensis oil, oil of Rhizoma Zingiberis Recens, Herba Schizonepetae oil, Fructus Forsythiae oil, press leaf oil, perilla oil, Oleum Citri Reticulatae, Oleum Viticis Negundo, Oleum Rosae Rugosae, Oleum Ricini, Oleum menthae, Artemisia anethoicles Mattf oil, fennel oil, pine oil, Oleum Caryophylli, Oleum Anisi Stellati, Oleum thymi vulgaris, Oleum Cinnamomi, Oleum Folium Artemisiae Argyi, Fructus Perillae oil, turmeric oil, Cortex Melaleucae leucadendrae oil, Essential lavender oil, Radix Aucklandiae oil, patchouli oil, Herba Verbenae oil, Common Wormwood oil, Salvia Sclare L.oil, Rhizoma Atractylodis oil, Myrtus communis oil, Fructus Citri Limoniae oil, long-pending real oil, Oleum Ocimi Gratissimi, Folium Perillae oil, art (pine) pomegranate oil, Oleum Cocois, Fructus Amomi oil, olive oil, citronella oil, Oleum Pelargonii Graveolentis, Herba Moslae oil, Oleum Menthae Rotundifoliae, Du Shan oil, Herba Pogostemonis oil, Storax oil, oil of Ribes nigrum L., Fructus Schisandrae oil, Rhizoma Acori Graminei oil, Fructus Cnidii oil, Fructus Phellodendri oil, Oleum lavandula angustifolia, oil of rosemary, oleum bergamottae, sandal oil, Fructus Dauci Sativae oil, Cacumen Cupressi oil, seed oil of Herba Apii graveolentis, Herba Origani oil, citronellal oil, orange blossom oil, nutmeg oil, oil of Bulbus Allii Cepae, Oleum Santali albi, Flos Tagetis Erectae oil, thyme oil, one or more in Cananga odorata oil.
The formula following (200ml submicron emulsion drug solution) of the best of the present invention
The effect of adjuvant in prescription is as follows:
Another object of the present invention is to provide the preparation method of submicron emulsion.
Preparation technology of the present invention, comprises the following steps::
By the antifungal drug of above-mentioned amount, lecithin, soybean oil, oleic acid, azone, the medicines such as vitamin E and natural essential oil add in ethanol, and heated and stirred makes it to dissolve completely.Separately get a certain amount of purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Whole production process be but its protection under carry out.
Concrete, the preparation technology of submicron emulsion of the present invention is as follows: by the antifungal drug of above-mentioned amount, lecithin, soybean oil, oleic acid, azone, VE and Herba Menthae wet goods medicine add (consumption of ethanol should be controlled the 10%-20% of the submicron emulsion medicine liquid volume for making) in ethanol, and heated and stirred makes it to dissolve completely.Separately get a certain amount of purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Whole production process be but its protection under carry out.
Concrete technological process is as follows:
1) first various prescriptions and adjuvant are ready to;
2) add ethanol heating (40 ± 2 DEG C), stir 15min and make it to dissolve completely;
3) collect above-mentioned ethanol drug solution;
4) separately get purified water, add glycerol;
5) under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution;
6) by homogenizer homogenizing 7-8 time of above-mentioned colostrum solution, pressure is 100MPa, at 180nm-300nm, obtains submicron emulsion drug solution to particle size range;
7) submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.
Final products are uniform milky solution, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Another object of the present invention is to provide the application of spray of the present invention in preparation antibacterials.
The present invention also provides the application of this spray in the medicine of preparation treatment dermatophytosis.Described tinea comprises: tinea pedis, tinea corporis and cruris, Tinea and microbid, tinea versicolor, tinea unguium, the tinea manuum, tinea pedis, tinea capitis.
The present invention combines antifungal drug, submicron emulsion and passs the advantage of medicine technology, transdermal enhancer, Derma-Guard and antioxidant and make spray.Said preparation both can be dispersed in fat-soluble medicine have been avoided in submicron emulsion using the cosolvent that has side effect, can increase again medicine Transdermal absorption, strengthen drug effect, extend action time.In addition phospholipid submicron emulsion has not only been avoided the stimulation of conventional dosage forms to skin, can also play skin care effect.
Brief description of the drawings
Preparation technology's flow chart of Fig. 1 submicron emulsion spray of the present invention.
Detailed description of the invention
Below in conjunction with embodiment, the present invention will be described in more detail.It should be understood that; the product of the embodiment of the present invention and preparation method are only used for illustrating the present invention; instead of limitation of the present invention, under design prerequisite of the present invention, the simple modifications of product of the present invention and preparation method is all belonged to the scope of protection of present invention.Except as otherwise noted, " % " in the present invention is all quality criterias.
Embodiment
Embodiment 1: the preparation of the different submicron emulsion product of antifungal drug consumption
In embodiment 1, to listed chemosynthesis antifungal drug, the amount ranges in prescription is verified.In the present embodiment, only taking the nitrate of miconazole as example, but amount ranges is applicable to the medicine of enumerating in all authority book.Under technology and condition of the present invention, submicron emulsion prescription immobilizes according to other components corresponding adjustment of consumption of miconazole nitrate medicine and consumption maintenance except lecithin consumption, and the consumption of chemical synthetic drug miconazole nitrate arbitrary consumption that volume ratio is calculated within the scope of 0.005-1.2% by weight all ensures to make stable final products.Although miconazole nitrate w/v can be made stable submicron emulsion medicinal liquid below 0.005% in principle, its liquor strength does not reach effective bacteriocidal concentration, without medicinal meaning, therefore investigate.
Embodiment 1.1: in submicron emulsion product, volume ratio contains 0.005% miconazole nitrate by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum menthae add 20ml ethanol, are heated to 45 DEG C of stirrings and make it to dissolve completely.Separately get 180ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 1.2: in submicron emulsion product, volume ratio contains 1.2% miconazole nitrate by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum menthae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 1.3: in submicron emulsion product, volume ratio contains 0.6% miconazole nitrate by weight.
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum menthae add 30ml ethanol, and heated and stirred is to dissolving completely.Separately get 170ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 2: the preparation of the different submicron emulsion product of supplementary product consumption
The present invention verifies the amount ranges of the each adjuvant of listed submicron emulsion.Under technology and condition of the present invention, keep the consumption of chemosynthesis antifungal drug w/v 1.2% to immobilize, volume ratio is calculated by weight, the consumption of lecithin is at 9.27-9.94%, and the consumption of soybean oil is at 0.5-5%, and the consumption of glycerol is 2.2%, the consumption of oleic acid is at 0-0.45%, the consumption of azone is at 0-0.01%, and the consumption of vitamin E is at 0-0.03%, and the arbitrary consumption of the consumption of Oleum menthae in the scope of 0-0.6% can be made stable final products.
Embodiment 2.1: in submicron emulsion product, volume ratio is calculated containing miconazole nitrate 1.2%, lecithin 9.50%, soybean oil 2.5%, glycerol 2.2%, oleic acid 0.25%, azone 0.005%, vitamin E 0.015% and Oleum menthae 0.3% by weight.
Submicron emulsion prescription (200ml medicine submicron emulsion medicinal liquid):
By recipe quantity miconazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum menthae add 30ml ethanol, and heated and stirred is to dissolving completely.Separately get 170ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 2.2: in submicron emulsion product, volume ratio is calculated containing miconazole nitrate 1.2%, lecithin 9.94%, soybean oil 5.0%, glycerol 2.2%, oleic acid 0.45%, azone 0.01%, vitamin E 0.03% and Oleum menthae 0.6% by weight.
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum menthae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 2.3: in submicron emulsion product, volume ratio is calculated containing miconazole nitrate 1.2%, lecithin 9.27%, soybean oil 0.5%, glycerol 2.2%, oleic acid 0.1%, azone 0.001%, vitamin E 0.003% and Oleum menthae 0.06% by weight.
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum menthae add 20ml ethanol, and heated and stirred is to dissolving completely.Separately get 180ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 3: use the preparation of the submicron emulsion product of different antifungal drugs
The listed various different synthetic drugs of the present invention are verified.Under technology and condition of the present invention, all ensure to make stable submicron emulsion preparation.
Embodiment 3.1: in submicron emulsion product, volume ratio is calculated containing 1.2% econazole nitrate by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity econazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum menthae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 3.2: in submicron emulsion product, volume ratio is calculated containing 1.2% itraconazole by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity itraconazole, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum menthae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 3.3: in submicron emulsion product, volume ratio is calculated containing 1.2% ketoconazole by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity ketoconazole, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum menthae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 4: use the preparation of the submicron emulsion product of different oil-soluble diluent
Embodiment 4.1: in submicron emulsion product, volume ratio is calculated containing 5% refined maize oil by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, refined maize oil, oleic acid, azone, vitamin E and Oleum menthae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 4.2: in submicron emulsion product, volume ratio is calculated containing 5% refining Oleum Brassicae campestris by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, refining Oleum Brassicae campestris, oleic acid, azone, vitamin E and Oleum menthae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 4.3: in submicron emulsion product, volume ratio is calculated containing 5% refining Oleum Arachidis hypogaeae semen by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, refining Oleum Arachidis hypogaeae semen, oleic acid, azone, vitamin E and Oleum menthae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 5: contain different natural essential oils in submicron emulsion product
Embodiment 5.1: in submicron emulsion product, volume ratio is calculated containing 0.15% Oleum Curcumae by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum Curcumae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 5.2: in submicron emulsion product, volume ratio is calculated containing 0.15% Oleum Hippophae by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Oleum Hippophae add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 5.3: in submicron emulsion product, volume ratio is calculated containing 0.15% Rhizoma Chuanxiong oil by weight
Submicron emulsion prescription (200mL submicron emulsion drug solution):
By recipe quantity miconazole nitrate, lecithin, soybean oil, oleic acid, azone, vitamin E and Rhizoma Chuanxiong oil add 40ml ethanol, and heated and stirred is to dissolving completely.Separately get 160ml purified water, add glycerol.Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution.Through high pressure homogenizer homogenizing 7-8 time, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.Final products should be uniform milky solutions, not precipitation and lamination.After the bottling of this product, should under 2 DEG C-15 DEG C and lucifuge condition, preserve.
Embodiment 1.2 submicron emulsion product extracorporeal antifungal activity experiments
At present for the drug sensitive experiment method of dermatophytosis unified, stable standard also in the world, but the liquid base dilution method M-38P that CLSI recommends and M-38A scheme are for detection of dermatophytosis, have obtained satisfied result
[5].Also has bibliographical information
[6]adopt the M-38P scheme that CLSI recommends to carry out the experimentation of extracorporeal antifungal activity to separating from the dermatophytosis of tinea pedis and body, tinea cruris, result shows that the M-38P scheme that CLSI recommends can, for dermatophytosis drug sensitivity testing in vitro, have good repeatability.Therefore the M-38P scheme that, adopts CLSI to recommend is herein carried out comparative study to the extracorporeal antifungal activity of miconazole nitrate crude drug, miconazole nitrate submicron emulsion spray, Miconazole Nitrate Cream agent.
Bibliographical information
[6]tinea pedis and tinea corporis and cruris pathogenic bacterium are the most common is trichophyton, accounting for 86.2%, is secondly alpha fungus (11.1%), acrothesium floccosum (1.4%), Sabouraudites lanosus (0.9%), Trichophyton violaceum (0.2%) and trichophyton (0.2%).Therefore the experimental strain of selecting trichophyton, alpha fungus, acrothesium floccosum to test as vitro Drug antifungal activity herein.
1, materials and methods
1.1 bacterium sources and grouping
Experimental strain is provided by foods in Shaanxi province institute for drug control, relates to altogether dermatophytosis 879 strains, wherein trichophyton 755 strains (86.2%), acrothesium floccosum 36 strains (4.0%) and alpha fungus 88 strains (9.8%).Miconazole nitrate crude drug group (I group) relates to dermatophytosis 307 strains, wherein trichophyton 268 strains, acrothesium floccosum 11 strains, alpha fungus 28 strains.Miconazole nitrate submicron emulsion spray preparation group (II group) relates to dermatophytosis 311 strains, wherein trichophyton 267 strains, acrothesium floccosum 9 strains, alpha fungus 35 strains.Commercially available Miconazole Nitrate Cream agent group (III group) relates to dermatophytosis 261 strains, wherein trichophyton 220 strains, acrothesium floccosum 16 strains, alpha fungus 25 strains.All strains examined, through the complete conformance with standard of characterization of biological feature, adopts the reference culture ATCC22019 of ATCC as Quality Control strain.
1.2 culture medium
Adopt RPMI1640 culture medium by the requirement of CLSI scheme.RPMI1640 powder (containing glutamine, not containing sodium bicarbonate) 10.9g, three nitrogen morpholine propane sulfonic acid (MOPS) 34.38g, distilled water 900mL, NaOH regulates pH to 7.0, is settled to 1000mL, by the sterile filters Entkeimung of diameter 0.2 μ m, put 4 DEG C of refrigerators for subsequent use.
1.3 medicine
I group: miconazole nitrate raw material is purchased from medicine company limited of Guangzhou Han Consulting;
II group: miconazole nitrate submicron emulsion spray preparation is standby by Xian Libang Pharmaceutical Co., Ltd.'s institute system; This Experimental agents is embodiment 1.2 spray preparations;
III group: commercially available Miconazole Nitrate Cream agent manufacturer is Xian-Janssen Pharmaceutical Ltd..
1.4 experimental technique
Medicinal liquid prepare medicine with dimethyl sulfoxide (DMSO) dissolve after, make doubling dilution (making DMSO concentration <1% after dilution) with RPMI1640 culture fluid, be added in aseptic 96 hole trace drug sensitive plates, every hole 100 μ L, screening mass concentration is 16～0.0003mg/L.And do blank and DMSO contrast, put-20 DEG C of Refrigerator stores for subsequent use.The Concentraton gradient of 3 groups of medicines is (mg/L): 16,8,4,2,1,0.5,0.25,0.125,0.06,0.03,0.015.
The purified rear transferred species of collecting cells dermatophytosis is hatched 7-10d in upper 30 DEG C of potato dextrose agar base (PDA).Get aseptic 0.85% saline of 1mL and repeatedly rinse bacterium colony surface, make bacteria suspension (1-5 × 10 of 0.5 Maxwell turbidity
6cFU/mL), this bacteria suspension is drawn to 2 times of final concentrations (0.4～5 × 10 with 50 times of RPMI1640 dilutions
5cFU/mL) bacteria suspension.
Inoculation adds bacteria suspension 0.1mL with the every hole of cultivation.Drug sensitive test plate is put into wet box, 30 DEG C of wave and culture not.
Result judges that dermatophytosis 5-7d reads result, carries out result judgement taking 50% inhibition as terminal.
2, result
Miconazole nitrate crude drug is 0.03-1mg/L to the MIC scope of dermatophytosis, MIC
50for 0.5mg/L, MIC
90for 1.0mg/L.Miconazole nitrate submicron emulsion spray is respectively 0.015-0.125mg/L, 0.03mg/L and 0.06mg/L.Miconazole Nitrate Cream is respectively 0.03-0.5mg/L, 0.125mg/L and 0.5mg/L.3 groups of medicines to the MIC measurement result of dermatophytosis in table 2.
The MIC measurement result (mg/L) of table 23 group medicine to dermatophytosis
MIC scope miconazole nitrate crude drug for trichophyton is 0.03-1mg/L, and miconazole nitrate submicron emulsion spray is 0.015-0.06mg/L, and Miconazole Nitrate Cream agent is 0.03-0.5mg/L.MIC scope miconazole nitrate raw material for acrothesium floccosum is 0.03-0.5mg/L, and miconazole nitrate submicron emulsion spray is 0.015-0.06mg/L, and Miconazole Nitrate Cream agent is 0.03-0.25mg/L.MIC scope miconazole nitrate raw material for alpha fungus is 0.03-1mg/L, and miconazole nitrate submicron emulsion spray is 0.015-0.125mg/L, and Miconazole Nitrate Cream is 0.03-0.25mg/L.3 groups of medicines to the MIC measurement result of dermatophytosis different strain in table 3.
Table 33 group medicine is measured (mg/L) to the MIC of dermatophytosis different strain
3, discuss
Draw by this experimentation, to the antibacterial activity in vitro of dermatophytosis by by force to a little less than be followed successively by miconazole nitrate submicron emulsion spray, Miconazole Nitrate Cream, miconazole nitrate crude drug.Visible, the extracorporeal antifungal activity of miconazole nitrate submicron emulsion spray is better than crude drug and ointment.Be expected to be developed to quick, the significant antifungal external used medicine of new curative effect.
The In Vitro Anti fungus experimental result of other embodiment submicron emulsion products
Adopt above-mentioned experimental technique, embodiment 1.1,1.3,3.1,3.2,3.3 submicron emulsion products are carried out to extracorporeal antifungal activity experiment, result is as follows:
The Concentraton gradient scope of medicine is (mg/L): 16,8,4,2,1,0.5,0.25,0.125,0.06,0.03,0.015.
1, the different submicron emulsion product In Vitro Anti fungus experimental result (mg/L) of miconazole nitrate consumption, in table 4.
The MIC measurement result (mg/L) of the different submicron emulsion product of table 4 miconazole nitrate consumption to dermatophytosis
2, the submicron emulsion product In Vitro Anti fungus experimental result (mg/L) of different antifungal drugs, in table 5.
The MIC measurement result (mg/L) of the submicron emulsion product of the different antifungal drugs of table 5 to dermatophytosis
In sum, submicron emulsion antifungal agent composition spray preparation of the present invention, has following four large advantages, 1, preparation includes antifungal drug and natural essential oil has bactericidal action, can not only Antifungi growth, and more really killing fungus, the performance efficacy of a drug, thus reach antipruritic effect; 2, submicron emulsion adopts the natural and synthetic composite multi-component penetration enhancer of phospholipid, book lotus oil, azone, oleic acid and ethanol composition can reach the incomparable effect of single penetration enhancer, strengthen the transdermal characteristic of product, being conducive to medicine arrives and accumulates in deep skin, thereby make sustained drug effectively bring into play the efficacy of a drug, can reduce again that medicine enters blood and the general toxicity that causes simultaneously; 3, instant effect; 4, the antioxidation of vitamin E and skin-nourishing effect play a protective role to skin.
List of references
[1] Wei Ke suzerain compiles, dermatological, and The Fourth Military Medical University publishes, 1986,56-57.
[2] Wei Ke suzerain compiles, dermatological, and The Fourth Military Medical University publishes, 1986,60-61.
[3] Chen Tao, Huimin power, Fu Jingguo, etc. the progress [J] of fat milk pharmaceutical preparation. the up-to-date medical information digest in the world, 2004,3 (5): 1295.
[4] Zhu Weiming. the progress of lipomul. Jiangsu Clinical Medical Journals, 2002,6 (2): 100-103.
[5] Zhao Jinghui, Sun Qiuning, Yan Yan, etc. the research [J] of common dermatophytosis In Vitro Chemosensitivity Test. Chinese mycology magazine, 2006,1 (4): 200-205.
[6] ten thousand Zhe, Wang Aiping, Chen Wei, Li Ruo fine jade .6 kind antifungal drug is evaluated [J] to dermatophytosis extracorporeal antifungal activity. Chinese mycology magazine, 2009,4 (4): 211-217.
Claims (10)
1. a submicron emulsion antifungal agent composition spray preparation, is characterized in that: fill a prescription composed as follows:
Be 0.005-1.2% (w/v) as the consumption of antifungal chemical synthetic drug;
Consumption as the lecithin of emulsifying agent, percutaneous absorption transdermal enhancers and Derma-Guard is 9.27-9.94% (w/v);
Be 0.5-5% (w/v) as the soybean oil of oil-soluble diluent or the consumption of other quintessence oils;
Consumption as the glycerol of isoosmotic adjusting agent is 2.2% (w/v);
Consumption as the oleic acid of co-emulsifier and percutaneous absorption transdermal enhancers is 0-0.45% (w/v);
Be 0-0.01% (w/v) as the consumption of percutaneous absorption transdermal enhancers azone;
Consumption as the vitamin E of antioxidant and Derma-Guard is 0-0.03% (w/v);
Consumption as the natural essential oil of percutaneous absorption transdermal enhancers, antimicrobial natural medicine and essence is 0-0.6% (w/v);
As the ethanol 10-20% of percutaneous absorption transdermal enhancers;
Surplus is water.
2. submicron emulsion antifungal agent composition spray preparation according to claim 1, it is characterized in that, saidly as antifungal drug be: one or more in miconazole, triaconazole, ECONAZOLE, ketoconazole, itraconazole, econazole, fluconazol, fenticonazole, sulconazole, tioconazole, Sertaconazole, terconazole (triaconazole), croconazole, isoconazole, fluorine triaconazole and their salt compound.
3. submicron emulsion antifungal agent composition spray preparation according to claim 1; it is characterized in that, the said lecithin as emulsifying agent, percutaneous absorption transdermal enhancers and Derma-Guard is: one or more in Ovum Gallus domesticus Flavus lecithin, soybean lecithin, hydrogenated yolk lecithin, hydrogenated soy phosphatidyl choline, synthetic lecithin, sphingomyelins.
4. submicron emulsion antifungal agent composition spray preparation according to claim 1, it is characterized in that, the said soybean oil as oil-soluble diluent or other quintessence oils are: any in refined soybean oil, refined maize oil, refining Oleum Helianthi, refining Oleum Arachidis hypogaeae semen, refining Oleum sesami, refining Oleum Brassicae campestris.
5. submicron emulsion antifungal agent composition spray preparation according to claim 1, is characterized in that, said as percutaneous absorption transdermal enhancers, the natural essential oil of antimicrobial natural medicine and essence is: Oleum Curcumae, Oleum Bulbus Allii, Rhizoma Chuanxiong oil, Herba Artemisiae Annuae oil, Oleum Hippophae, wintergreen oil, Radix Oenotherae erythrosepalae pool, Radix Angelicae Sinensis oil, oil of Rhizoma Zingiberis Recens, Herba Schizonepetae oil, Fructus Forsythiae oil, press leaf oil, perilla oil, Oleum Citri Reticulatae, Oleum Viticis Negundo, Oleum Rosae Rugosae, Oleum Ricini, Oleum menthae, Artemisia anethoicles Mattf oil, fennel oil, pine oil, Oleum Caryophylli, Oleum Anisi Stellati, Oleum thymi vulgaris, Oleum Cinnamomi, Oleum Folium Artemisiae Argyi, Fructus Perillae oil, turmeric oil, Cortex Melaleucae leucadendrae oil, Essential lavender oil, Radix Aucklandiae oil, patchouli oil, Herba Verbenae oil, Common Wormwood oil, Salvia Sclare L.oil, Rhizoma Atractylodis oil, Myrtus communis oil, Fructus Citri Limoniae oil, long-pending real oil, Oleum Ocimi Gratissimi, Folium Perillae oil, art (pine) pomegranate oil, Oleum Cocois, Fructus Amomi oil, olive oil, citronella oil, Oleum Pelargonii Graveolentis, Herba Moslae oil, Oleum Menthae Rotundifoliae, Du Shan oil, Herba Pogostemonis oil, Storax oil, oil of Ribes nigrum L., Fructus Schisandrae oil, Rhizoma Acori Graminei oil, Fructus Cnidii oil, Fructus Phellodendri oil, Oleum lavandula angustifolia, oil of rosemary, oleum bergamottae, sandal oil, Fructus Dauci Sativae oil, Cacumen Cupressi oil, seed oil of Herba Apii graveolentis, Herba Origani oil, citronellal oil, orange blossom oil, nutmeg oil, oil of Bulbus Allii Cepae, Oleum Santali albi, Flos Tagetis Erectae oil, thyme oil, one or more in Cananga odorata oil.
6. submicron emulsion antifungal agent composition spray preparation according to claim 1, is characterized in that, fills a prescription composed as follows:
7. the preparation method of submicron emulsion antifungal agent composition spray preparation, it is characterized in that, by the antifungal drug of described amount, lecithin, soybean oil, oleic acid, azone, VE and Herba Menthae wet goods medicine add in ethanol, and wherein the consumption of ethanol is the 10%-20% of the submicron emulsion medicine liquid volume made, and heated and stirred makes it to dissolve completely;
Separately get a certain amount of purified water, add glycerol;
Under the condition of nitrogen protection, ethanol drug solution is added in the glycerine water solution by cutter high-speed stirred (3000r/rnin) slowly, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution; Through high pressure homogenizer homogenizing, pressure is 100MPa, and to particle size range, at 180nm-300nm, submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products;
Whole production process is to carry out under nitrogen protection.
8. preparation method as claimed in claim 7, is characterized in that:
1) first various prescriptions and adjuvant are ready to;
2) add ethanol and be heated to 40 ± 2 DEG C, stirring 15min and make it to dissolve completely;
3) collect above-mentioned ethanol drug solution;
4) separately get purified water, add glycerol;
5) under the condition of nitrogen protection, ethanol drug solution is added slowly in the glycerine water solution stirring with the speed of 3000r/rnin with cutter, under the condition of nitrogen protection, continue to stir 30min, obtain colostrum solution;
6) by homogenizer homogenizing 7-8 time of above-mentioned colostrum solution, pressure is 100MPa, at 180nm-300nm, obtains submicron emulsion drug solution to particle size range;
7) submicron emulsion drug solution is diluted to final liquor strength with pure water and obtains final products.
9. the application of spray claimed in claim 1 in preparation antibacterials.
10. the application of spray claimed in claim 1 in the medicine of preparation treatment dermatophytosis.
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