A kind of dermopathic composition of external curingTechnical field
Dermopathic medicine, particularly a kind of external curing skin disease containing PVP-I are treated the present invention relates to one kindComposition.
Background technology
At present, the nosomycosis that the mankind can suffer from can generally be divided into following four classes：Studies of invasive fungal infections with it is systemic trueBacterium disease (such as aspergillosis and candidiasis), mucosal pattern nosomycosis (such as " thrush "), superficial type dermatomycosis are (such as " perfumeHong Kong-feet ", " onychomycosis ", all kinds of " skin tineas " etc.) and anaphylactic type nosomycosis (such as asthma and chronic inflammation).First kind nosomycosisHarm is big, it is necessary to which antifungal drug complex treatment for oral administration, mucous membrane type nosomycosis and superficial type dermatomycosis are controlled except medicine for oral administrationTreat, more convenient and simple and direct is to use external medication.Many disease of skin, often bacterium and the compound sense of fungiDye, or fungal infection is formerly, causes the wound supervention bacterium infection after cuticular breakdown.Therefore only it is single it is antimycotic effectively intoPoint outer there is ointment, spray, liniment, daubing medicament to treat the skin that there is bacterium and fungi compound infection quickly, in timeDisease.
The content of the invention
For above-mentioned the deficiencies in the prior art, the invention provides a kind of dermopathic composition of external curing,The skin disease of various skin tinea diseases and fungi bacterium compound infection can effectively be treated.
The dermopathic composition of a kind of external curing that the present invention is provided, by active ingredient and pharmaceutically acceptable auxiliaryMaterial composition, it is characterised in that the active ingredient of composition include PVP-I, imidazoles and/or antifungal drug in triazole class withAnd skin penetrant, available iodine content and imidazoles and/or antifungal drug in triazole class and skin in the PVP-IThe mass ratio of bleeding agent is (3~200):(2~400):(10~1600)；The skin disease is that fungi and/or bacterium infection are drawnThe skin disease risen.
Preferably, the PVP-I is calculated with available iodine content, accounts for the 0.03~2% of composition total weight.
Preferably, the imidazoles antifungal drug is clotrimazole, Miconazole, econazole, ketoconazole, tioconazole, Bu KangOne or more of mixtures in azoles, sulconazole, Oxiconazole and bifonazole；Antifungal drug in triazole class be Fluconazole,One or more of mixture in Itraconazole and terconazole；Imidazoles and/or the weight of antifungal drug in triazole class account for combinationThe 0.02~4% of thing gross weight.
Preferably, the antifungal drug in the active ingredient is one kind in following mixture：
The mixture of miconazole nitrate and Itraconazole, both mass ratioes are 1:1；
The mixture of voriconazole and econazole, both mass ratioes are 1:1；
The mixture of voriconazole and miconazole nitrate, both mass ratioes are 1:1.
Preferably, the skin penetrant is mixture one or more in following component：With saturated alkane baseAzone class, pyrrolones, fitter acids and its ester class, alcohols and polyalcohols, sulfoxide type, amine and amide-type, terpene.
Preferably, the skin penetrant is Laurocapram, accounts for composition total weight 0.1%~3.0%.
Preferably, the skin penetrant is methyl laurate, accounts for composition total weight 1%~8%.
Preferably, the skin penetrant is one kind in following mixture：
The mixture of Laurocapram and menthol, Laurocapram weight account for composition total weight 0.1%~3.0%, menthol weight accounts for the 1%~5% of composition total weight；
Laurocapram and lauric mixture, Laurocapram weight account for composition total weight 0.1%~3.0%, laurate weight accounts for the 1%~8% of composition total weight；
The mixture of laurate and methyl laurate, both respectively account for composition total weight 1%~8%.
Preferably, containing the iodine stabilizer for accounting for composition total weight 0.02~1.0% in the auxiliary material of composition, for controllingEffective iodine concentration of PVP-I is stable in composition, and the iodine stabilizer is that Potassiumiodate and/or Potassiumiodate are combined with KIThing, consumption preferably is 0.05~0.5%.
, can be from including but not limited to sodium dihydrogen phosphate and phosphorus in a kind of dermopathic composition of external curing of the present inventionThe pH value of sour disodium hydrogen buffer system regulation composition preparation is in the range of 5.0-8.0, preferably in 6.0-7.0.
(surface can be included but is not limited to from suitable medical processing aid known to pharmaceutical industry in above-mentioned compositionActivating agent, thickener, excipient, dispersant, foaming agent etc.) and processing method, is processed into and (does not limit including of facilitating patient to useIn) formulation such as ointment, spray, aqueous pharmaceutical, liniment, pulvis, suppository；Or combined with dressing carrier be made application,Plaster etc..
The composition of the present invention can be used for what is contained in external curing tinea pedis (tinea pedis, athlete's foot), composition pharmaceutically may be usedThe auxiliary material of receiving can make composition be prepared into appropriate preparation (aqua, ointment, liniment, spray, ointment agent, containing medicamentDressing), composite preparation is directly applied at the sufferer of tinea pedis with known various modes.
The composition of the present invention can be with the various dermatophytosis of external curing (such as favus of the scalp, ringworm of the body, jock itch, the tinea manuum, firstTinea, tinea versicolor, dermatophytids), preparation (aqua, ointment, liniment, spraying that can be appropriate by pharmaceutically acceptable auxiliary materialAgent), it is directly applied to known various modes at the sufferer of all kinds of skin tineas.
It is all kinds of that the composition of the present invention can be also used for the various malignant boils caused by bacterium infection of external curing, sore, furuncle, swollen etc.Skin disease, can select the preparation (aqua, ointment, liniment, spray, ointment agent, the dressing containing medicament) of appropriately combined thing,It is directly applied to known various modes at the sufferer of skin.
The composition of the present invention can be also used for external curing because fungi (such as monilial infection) infects and/or bacterium senseThe gynaecology's vulvitis and vaginitis disease of dye, can select appropriate preparation (aqua, ointment, suppository, irrigation etc.), with public affairsThe various modes known are directly applied to be put into intravaginal at sufferer or with suppository.
The dermopathic composition of a kind of external curing that the present invention is provided, has the advantages that：
(1) PVP-I is used in being formulated as dermopathic active drug component is treated, with antifungal drug imidazolesSynergy is played with triazole type medicine compatibility, skin disease is used for outside and suffers from part, all kinds of dermatophytosis is treated and furunculosis furuncle is thinBacterium infective factors.
(2) imidazoles and the reasonable combination of antifungal drug in triazole class are arranged in pairs or groups in recipe ingredient, for treating mucosal patternWith superficial type fungi and the skin disease of bacterium infection, it is to avoid by oral administration or injection use imidazoles and antifungal drug in triazole class pairThe toxic side effect of body.
(3) each component in skin penetrant can play collaboration osmosis, by the transdermal penetration for improving drug componentEffect enhancing drug effect, can be simultaneously reached the target of the usage amount of reduction drug component.
(4) composite skin disease caused by fungi and bacterium infection, and instant effect can be effectively treated, will not be answered after healingHair.
Embodiment
In order that those skilled in the art will better understand the technical solution of the present invention, with reference to embodimentThe present invention is described in further detail.
Embodiment 1
The dermopathic composition containing PVP-I of external curing, is formulated on the basis of the ointment according to total amount 1000g, whereinThe consumption proportion of various components is as follows：
PVP-I pulvis (containing available iodine 10%) 50g
Itraconazole (Itraconazole) 15g
Miconazole nitrate (Miconazole Nitrate) 15g
Laurocapram (Laurocapram) 20g
Potassiumiodate 2g
PH buffer (sodium dihydrogen phosphate/disodium hydrogen phosphate) is appropriate (regulation pH=6-7)
Purified water 440g
Processing aid is (glycerin monostearate 15g, stearic acid 10g, triethanolamine 10g, glycerine 5g, ethyl hydroxy benzoate 3g, whiteVaseline 60, liquid paraffin 350, double stearic acid aluminium 5g)
It is formulated total amount and adds up to 1000g
In 3000ml beakers, the processing aid and Itraconazole (Itraconazole) nitric acid miaow of above-mentioned formula ratio are put intoHealth azoles (Miconazole Nitrate) Laurocapram (Laurocapram) Potassiumiodate, is heated to 80-85 DEG C of fusing, stirringUniformly；
440ml pure water and 50g PVP-Is are added in another 1000ml beakers, stirring and dissolving obtains dark-brown completelyBetagen Solution；
By the Betagen Solution dissolved, it is poured slowly under agitation in the beaker for having dissolved processing aid, stirring is mixedClose, beaten and be well mixed with miniature high-speed shearing emulsifier, according to the sodium dihydrogen phosphate/phosphoric acid hydrogen of method known to pharmaceutical industryDisodium buffer system regulation system pH=6-7, is made the dermopathic composition containing PVP-I of oiliness external curing.Said compositionIt is particularly suitable for the treatment scales of skin that peel off keratinization type ringworm of the foot (tinea pedis), affected part is applied directly to when using.
Embodiment 2：
The dermopathic composition containing PVP-I of external curing, on the basis of formula is according to total amount 1000g ointments, various groupsDivide consumption proportion as follows：
PVP-I pulvis (containing available iodine 10%) 50g
Voriconazole (Voriconazole) 15g
Econazole (Econazole) 15g
Laurocapram (Laurocapram) 20g
Propane diols 10g
Potassiumiodate 2g
PH buffer (sodium dihydrogen phosphate/disodium hydrogen phosphate) is appropriate (regulation pH=6-7)
Purified water 638g
Processing aid (sodium carboxymethylcellulose (CMC) 50g, polyethylene glycol (2000) 100g, glycerine 100g)
Total amount is formulated to add up to：1000g
Auxiliary agent polyethylene glycol, voriconazole, econazole, Laurocapram, propane diols and iodine are put into 3000ml beakersSour potassium, is heated to polyethylene glycol fusing, and mixture stirs.
PVP-I pulvis 50g and sodium carboxymethylcellulose 50g are mixed and added into glycerine 100g, mortar in mortarGrind and be mixed even, be gradually added purified water and grind after mixed general uniform, close the lid, allow PVP-I and carboxymethyl cellulose to absorb waterFully be swelled, then grind again be mixed it is even be paste.
Two pre-formed components are mixed, grind be mixed it is even, according to the sodium dihydrogen phosphate/phosphoric acid hydrogen of method known to pharmaceutical industryDisodium buffer system regulation system pH=6-7, is made the dermopathic paste of composition containing PVP-I of water-soluble external curing.ShouldComposition festers type and the bubble type ringworm of the foot (tinea pedis), and the skin disease such as skin furunculosis furuncle caused by bacterium infection suitable for treatmentDisease, is applied directly to affected part when using.
Embodiment 3：
The dermopathic composition containing PVP-I of external curing, on the basis of formula is according to total amount 1000g thickening type aquas, respectivelyThe consumption proportion for planting component is as follows：
PVP-I pulvis (containing available iodine 10%) 50g
Voriconazole (Voriconazole) 15g
Miconazole nitrate (Miconazole Nitrate) 15g
Laurocapram (Laurocapram) 20g
Menthol 10g
Potassiumiodate 2g
PH buffer (sodium dihydrogen phosphate/disodium hydrogen phosphate) is appropriate (regulation pH=6-7)
Purified water 768g
(5g, sodium carboxymethylcellulose (CMC) 10g are sweet for lauryl sodium sulfate 5g, glycerin monostearate for processing aidOily 100g)
PVP-I, Potassiumiodate, lauryl sodium sulfate, glycerin monostearate and carboxylic first are added in 3000ml beakersBase sodium cellulosate, adds purified water, and the lower dissolving of stirring is complete；
Glycerine and voriconazole, miconazole nitrate, Laurocapram and menthol are put into mortar, grind be mixed it is even after plusEnter in prefabricated aqueous phase, stirring and emulsifying is uniform (preparing more convenient and quicker using small-sized high-shear emulsifying agent), according to pharmacy rowSodium dihydrogen phosphate/disodium hydrogen phosphate buffer system regulation system the pH=6-7 of method known to industry, prepares external curing skinThe viscous water dosage formulation of composition containing PVP-I of skin disease.It can be used for all kinds of dermatophytosis and furunculosis furuncle be dermopathic controlsTreat.Medicament can be dipped with cotton swab, be applied directly to affected part, or upper medicament is soaked with gauze, cover or be wrapped in skin affected part.
Embodiment 4：
The dermopathic composition containing PVP-I of external curing, on the basis of formula is according to total amount 1000g aquas, various componentsProportioning it is as follows：
PVP-I pulvis (containing available iodine 10%) 50g
Miconazole nitrate (Miconazole Nitrate) 20g
Laurocapram (Laurocapram) 20g
Propane diols 10g
Potassiumiodate 1g
PH buffer (sodium dihydrogen phosphate/disodium hydrogen phosphate) is appropriate (regulation pH=5-6)
Purified water 790g
Processing aid (lauryl sodium sulfate 5g, glycerin monostearate, 4g, glycerine 100g)
PVP-I, Potassiumiodate, lauryl sodium sulfate, glycerin monostearate are added in 3000ml beakers, is addedPurified water, the lower dissolving of stirring is complete；
Glycerine and miconazole nitrate, Laurocapram and propane diols are put into mortar, the even rear addition that is mixed is ground prefabricatedAqueous phase in, stirring and emulsifying is uniform (preparing more convenient and quicker using small-sized high-shear emulsifying agent), according to known to pharmaceutical industryMethod sodium dihydrogen phosphate/disodium hydrogen phosphate buffer system regulation system pH=5-6, prepares that external curing is dermopathic to be containedPVP-I composition water aqua type preparation.It can be used for all kinds of dermatophytosis and furunculosis furuncle treating for skin disease.Cotton can be usedLabel dip medicament, are applied directly to affected part, or soak upper medicament with gauze, cover or be wrapped in skin affected part.
Embodiment 5：
The dermopathic composition containing PVP-I of external curing, formula is example, various groups according to total amount 1000g ointmentsThe consumption proportion divided is as follows：
PVP-I pulvis (containing available iodine 10%) 50g
Itraconazole (Itraconazole) 15g
Laurocapram (Laurocapram) 20g
Stearic acid 10g
Potassiumiodate 2g
PH buffer (sodium dihydrogen phosphate/disodium hydrogen phosphate) is appropriate (regulation pH=6-7)
Purified water 455g
Processing aid (glycerin monostearate 15g, triethanolamine 10g, glycerine 5g, ethyl hydroxy benzoate 3g, albolene 60,Liquid paraffin 350, double stearic acid aluminium 5g)
It is formulated total amount and adds up to 1000g
In 3000ml beakers, the processing aid and Itraconazole (Itraconazole) bay nitrogen of above-mentioned formula ratio are put intoTall and erect ketone (Laurocapram) stearic acid, is heated to 80-85 DEG C of fusing, stirs；
455ml pure water and 50g PVP-Is and Potassiumiodate are added in another 1000ml beakers, stirring and dissolving is obtained completelyTo dark-brown Betagen Solution；
By the Betagen Solution dissolved, it is poured slowly under agitation in the beaker for having dissolved processing aid, stirring is mixedClose, beaten and be well mixed with miniature high-speed shearing emulsifier, according to the sodium dihydrogen phosphate/phosphoric acid hydrogen of method known to pharmaceutical industryDisodium buffer system regulation system pH=6-7, is made the dermopathic composition containing PVP-I of oiliness external curing.Said compositionIt is suitable for treating non-ulcer type dermatophytosis, affected part is applied directly to when using.
Embodiment 6
The dermopathic composition containing PVP-I of external curing, formula is example, various groups according to total amount 1000g ointmentsThe consumption proportion divided is as follows：
PVP-I pulvis (containing available iodine 10%) 50g
Itraconazole (Itraconazole) 15g
Laurocapram (Laurocapram) 20g
Laurate 20g
Potassiumiodate 2g
PH buffer (sodium dihydrogen phosphate/disodium hydrogen phosphate) is appropriate (regulation pH=6-7)
Purified water 445g
Processing aid (glycerin monostearate 15g, triethanolamine 10g, glycerine 5g, ethyl hydroxy benzoate 3g, albolene 60,Liquid paraffin 350, double stearic acid aluminium 5g)
It is formulated total amount and adds up to 1000g
In 3000ml beakers, the processing aid and Itraconazole (Itraconazole) bay nitrogen of above-mentioned formula ratio are put intoTall and erect ketone (Laurocapram) laurate, is heated to 80-85 DEG C of fusing, stirs；
445ml pure water and 50g PVP-Is and Potassiumiodate are added in another 1000ml beakers, stirring and dissolving is obtained completelyTo dark-brown Betagen Solution；
By the Betagen Solution dissolved, it is poured slowly under agitation in the beaker for having dissolved processing aid, stirring is mixedClose, beaten and be well mixed with miniature high-speed shearing emulsifier, according to the sodium dihydrogen phosphate/phosphoric acid hydrogen of method known to pharmaceutical industryDisodium buffer system regulation system pH=6-7, is made the dermopathic composition containing PVP-I of oiliness external curing.Said compositionIt is suitable for treating non-ulcer type dermatophytosis, affected part is applied directly to when using.
Embodiment 7
The dermopathic composition containing PVP-I of external curing, formula is example, various groups according to total amount 1000g ointmentsThe consumption proportion divided is as follows：
PVP-I pulvis (containing available iodine 10%) 50g
Itraconazole (Itraconazole) 15g
Methyl laurate 30g
Potassiumiodate 2g
PH buffer (sodium dihydrogen phosphate/disodium hydrogen phosphate) is appropriate (regulation pH=6-7)
Purified water 455g
Processing aid (glycerin monostearate 15g, triethanolamine 10g, glycerine 5g, ethyl hydroxy benzoate 3g, albolene 60,Liquid paraffin 350, double stearic acid aluminium 5g)
It is formulated total amount and adds up to 1000g
In 3000ml beakers, the processing aid and Itraconazole (Itraconazole) laurate of above-mentioned formula ratio are put intoMethyl esters, is heated to 80-85 DEG C of fusing, stirs；
455ml pure water and 50g PVP-Is and Potassiumiodate are added in another 1000ml beakers, stirring and dissolving is obtained completelyTo dark-brown Betagen Solution；
By the Betagen Solution dissolved, it is poured slowly under agitation in the beaker for having dissolved processing aid, stirring is mixedClose, beaten and be well mixed with miniature high-speed shearing emulsifier, according to the sodium dihydrogen phosphate/phosphoric acid hydrogen of method known to pharmaceutical industryDisodium buffer system regulation system pH=6-7, is made the dermopathic composition containing PVP-I of oiliness external curing.Said compositionIt is suitable for treating non-ulcer type dermatophytosis, affected part is applied directly to when using.
Embodiment 8
The dermopathic composition containing PVP-I of external curing, formula is example, various groups according to total amount 1000g ointmentsThe consumption proportion divided is as follows：
PVP-I pulvis (containing available iodine 10%) 50g
Itraconazole (Itraconazole) 15g
Methyl laurate 30g
Laurate 20g
Potassiumiodate 2g
PH buffer (sodium dihydrogen phosphate/disodium hydrogen phosphate) is appropriate (regulation pH=6-7)
Purified water 435g
Processing aid (glycerin monostearate 15g, triethanolamine 10g, glycerine 5g, ethyl hydroxy benzoate 3g, albolene 60,Liquid paraffin 350, double stearic acid aluminium 5g)
It is formulated total amount and adds up to 1000g
In 3000ml beakers, the processing aid and Itraconazole (Itraconazole) laurate of above-mentioned formula ratio are put intoMethyl esters and laurate, are heated to 80-85 DEG C of fusing, stir；
435ml pure water and 50g PVP-Is and Potassiumiodate are added in another 1000ml beakers, stirring and dissolving is obtained completelyTo dark-brown Betagen Solution；
By the Betagen Solution dissolved, it is poured slowly under agitation in the beaker for having dissolved processing aid, stirring is mixedClose, beaten and be well mixed with miniature high-speed shearing emulsifier, according to the sodium dihydrogen phosphate/phosphoric acid hydrogen of method known to pharmaceutical industryDisodium buffer system regulation system pH=6-7, is made the dermopathic composition containing PVP-I of oiliness external curing.Said compositionIt is suitable for treating non-ulcer type dermatophytosis, affected part is applied directly to when using.
Case 1
Slowly certain, 31 years old, male, with the scales of skin that peel off keratinization type ringworm of the foot (tinea pedis) 6 years, the excessively a variety of antimycotic marketed drugs of useEqual symptom makes moderate progress, and is recurred after drug withdrawal.The medicine of the offer of the embodiment of the present invention 1 is used in last medication instead after 30 days, daily coatingRemission in affected part 2 times, each consumption 12-15g, 24h, the ringworm of the foot is fully erased after January, and follow-up is not recurred for 9 months.
Case 2
Often certain, 19 years old, male, with festering type and the bubble type ringworm of the foot from 16 years old, both alternately mixing breaking-outs connect for a long timeIt is not obviously improved by commercially available for oral administration/external medication, the medicine of the offer of the embodiment of the present invention 2 is used in last medication instead after 30 daysThing, coats affected part twice daily, each consumption 12-15g, remission in 48h, and the ringworm of the foot is fully erased after 2 weeks, follow-up 11 monthsDo not recur afterwards.
Case 3
Zhang, 27 years old, women, with tinea versicolor 3 years, received commercially available for oral administration/external medication and substantially not changed for a long timeKind, the medicine of the offer of the embodiment of the present invention 3 is used in last medication instead after 30 days, coat affected part twice daily, each consumption 12-15g,Remission in 48h, the fully erased recovery from illness of tinea versicolor after 2 weeks, follow-up is not recurred after 11 months.
Case 4
Ke, 52 years old, male, belly and lower limb suffered from fash 4 years, and a variety of external medications of layer receiving are invalid, useThe medicine that the embodiment of the present invention 6 is provided, coats affected part 3 times daily, each consumption 12-15g, remission, skin after 12 days in 24hRash is fully erased, and follow-up is not recurred after 8 months.
Test example 1
Zoopery：
Kunming mice 90 is chosen, male and female are random, are divided into 9 groups, back unhairing, with No. 200 sand paper scratch, connects simultaneouslyKind of alpha fungus and staphylococcus aureus, set up mouse fungi, bacterium compound infection model, and 1~8 group is respectively coated and usesThe medicine that embodiment 1~8 is provided, the 9th group is used as blank control group.Administration 3~7 days, observation mouse skin damaged improve and fungi andBacterium removes situation.As a result record in table 1 below
The results of animal of table 1
As seen from the above table, the composition medicament that provides of the present invention can be caused by fast treating fungi and bacterium compound infectionMedication effect in disease of skin, embodiment 3 is the most notable, just almost completely can be by fungi and thin after medication 72hBacterium is all removed, and is taken effect and is exceedingly fast.
A kind of dermopathic composition of external curing provided by the present invention is described in detail above.Herein shouldThe principle and embodiment of the present invention are set forth with specific case, the explanation of above example is only intended to help and managedSolve the core concept of the present invention.It should be pointed out that for those skilled in the art, not departing from original of the inventionOn the premise of reason, some improvement and modification can also be carried out to the present invention.These are improved and modification should also be as falling into power of the present inventionIn the protection domain that profit is required.