CN108472313A - Compositions and methods for treating otitis - Google Patents

Compositions and methods for treating otitis Download PDF

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Publication number
CN108472313A
CN108472313A CN201780002919.6A CN201780002919A CN108472313A CN 108472313 A CN108472313 A CN 108472313A CN 201780002919 A CN201780002919 A CN 201780002919A CN 108472313 A CN108472313 A CN 108472313A
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China
Prior art keywords
composition
dmso
pvp
infection
agent
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CN201780002919.6A
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Chinese (zh)
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约瑟夫·卡普里奥蒂
卡拉·卡普里奥蒂
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Veloce Biopharma LLC
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Veloce Biopharma LLC
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Priority claimed from US15/341,930 external-priority patent/US20170071979A1/en
Application filed by Veloce Biopharma LLC filed Critical Veloce Biopharma LLC
Publication of CN108472313A publication Critical patent/CN108472313A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/04—Amoebicides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/18—Iodine; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0046—Ear
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Abstract

The present invention relates to compositions and methods for treating otic infections, including otitis externa or otitis media, comprising povidone-iodine and dimethyl sulfoxide (DMSO) and optionally a gelling agent.

Description

Composition for treating otitis and method
Background
The infection of millions of mankind patients ducts or inflammation, external ear (otitis externa) or middle ear (tympanitis).For this The purpose of theme invention, these situations can be collectively known as " otitis ".Otitis can be acute or chronic, and can Exudation can be presented.
Current therapeutic for the bacterium infection of duct, fungal infection/yeast infection and virus infection may be invalid , because they only treat the subset of the pathogen of infection.Many current treatments include unacceptable ingredient, such as steroids Or other potentially harmful components.
For example, U.S. Patent Application Publication the 2009/0263345th；No. 2012/0003174；With the 2013/th No. 0089510 describes using PVP-I and steroid therapy otitis.According to these applications, otitis externa (external ear infection) is external ear With the inflammation of duct.It is the common disease factor of human middle ear's pain, and is the FAQs in dog, cat and other mammals. It also occurs in many other species.This disorder is related to the inflammation of the skin of duct.Inflammation can by fungi living, virus or Bacterial organisms cause.Ear channel skin usually swelling, and may become pain and one touch i.e. pain (tender) without It can touch.
Tympanitis (middle ear infection) is happened at the region between eardrum and inner ear, including Eustachian tube.Tympanitis is in children Phase is very common, and 1 year experience of average child is nearly always accompanied by viral upper respiratory sense twice to breaking out three times It contaminates (URI), mainly common cold.The rhinovirus of many common cold symptoms and adenovirus is caused to cause interior ear swelling and fill Blood, this possible permanent damage middle ear structure.Tympanitis is also often caused by many bacteriums and other viruses.
Further, since antibiotic resistant bacteria (antibiotic resistant bacteria) and antibiotics resistance are micro- Biological (antibiotic-resistant microorganism), ear infection (especially children) is to have changed into be difficult to use One kind in many diseases of conventional antibiotic drug therapy.For example, many situations of tympanitis are by several the main pathogenic fungis One kind cause, streptococcus pneumonia (Streptococcus pneumoniae), haemophilus influenzae (Haemophilus Influenza), catarrh Moraxella (Moraxella catarrhalia), staphylococcus aureus (Staphylococcus aureus), staphylococcus epidermis (Staphylococcus epidermidis) or Pseudomonas aeruginosa (Pseudomonas aeruginosa)。
Therefore, in view of known antibiotic resistance, steroids potentially harmful side effect the shortcomings that or similar disadvantage (these disadvantages may include that the antibiotic of routine or the composition of steroids cause by using), prevents exploitation and manages this There is an urgent need for the new method of a little diseases, and the new method need not use conventional antibiotic or steroids.
Discovery nearest Capriotti et al. has been disclosed for composition, and the composition includes Iodophor such as povidone- Iodine (PVP-I) and dimethyl sulfoxide (DMSO) (DMSO), the Iodophor are used as active constituent as active constituent, the dimethyl sulfoxide (DMSO) Penetration enhancers (penetration enhancer).These compositions are shown the fungi sense for treating skin and nail Dye is useful.No. US2014/0205559 (Capriotti ' 559) is announced see, for example, the U.S., the announcement is integrally logical with it It crosses and is incorporated herein by reference.PVP-I is well known preservative, is had for viral species, fungal species and bacterial species and compacted The broad spectrum of activity of shape mite (demodex), and do not have known bacterial drug resistance, Antifungal resistance or virus drug resistance. PVP-I is also shown as inhibiting the formation of biomembrane and eliminates the biomembrane formed.
The percutaneous absorbtion of known a variety of organic solvents enhancing some drugs including dimethyl sulfoxide (DMSO) (DMSO).However, Through being received for a long time in drug field, DMSO enhances oozing for small molecule or low molecular weight (LMW) compound or drug Thoroughly, but without effectively enhancing it is greater than about the infiltration of high molecular weight (HMW) the compound such as polymer of 10,000 dalton.
U.S. Patent Publication the 2009/0263345th；No. 2012/0003174；Do not have with No. 2013/0089510 Description without steroid compositions (steroid-free composition), and do not recognize or be expected such as to be described herein and The advantages of claimed composition comprising PVP-I and DMSO for treating otitis.
Summary
The composition of the subject innovation can be in virus infection, fungi or yeast infection, the bacterium for treating duct It is useful in infection or amoeba infection or the method infected.
The topical composition of the subject innovation include about 0.1% to about 10% povidone iodine (PVP-I) and about 30% to About 99% dimethyl sulfoxide (DMSO) (DMSO).The topical gel composition of the subject innovation includes about 0.1% to about 10% poly- dimension Ketone iodine (PVP-I), about 30% to about 99% dimethyl sulfoxide (DMSO) (DMSO) and about 1% to about 10% gelling agent.With generally Non-gelling agent and include about 0.1% to about 10% povidone-iodine and about 30% to about 99% DMSO liquid composition It compares, the effect of topical gel composition of the invention unexpectedly can show bigger in treating otitis.This theme The topical gel composition of invention is unexpectedly highly stable in room temperature, in aqueous ingredients or without water constituent in the presence of 's.
Preferred composition includes the PVP-I of about 0.25% to about 0.35%.Another preferred composition include with The PVP-I of 0.25% to about 0.5%, another composition include the PVP-I of 1% to about 5%.Preferred composition can wrap Containing about 1% PVP-I or about 2% PVP-I.Using K30 povidone grade PVP-I for making in this theme composition With being preferred.
Preferred composition includes the DMSO of about 30% to about 70%.Preferred composition can include about 40% to about 49% DMSO, and even more preferably about 44% DMSO.
Preferred composition includes the gelling agent of about 0.5% to about 5%.Preferred composition can include about 1%- 2% gelling agent.The particularly useful composition for being prepared for test includes 2% PVP-I；44% DMSO；2% Hydroxyethyl cellulose；With 52% aqueous solvent (aqueous solvent).Preferred aqueous solvent is water or isotonic buffer Liquid.
The present invention composition can include gelling agent well known in the art, the gelling agent can be selected from natural gum, agar, Carrageenan, vaseline or cellulosic polymer or the like.A kind of preferred cellulosic polymer as gelling agent is hydroxyl Ethyl cellulose.Selectable cellulosic polymer gelling agent is hydroxymethyl cellulose.
The composition of the present invention preferably includes povidone-iodine or PVP-I with the average molecular weight more than 10,000. It is highly preferred that the composition of the present invention includes the PVP- with the average molecular weight between about 20,000 to about 1,000,000 I.One preferred embodiment includes having between about 30,000 to about 60,000 or the PVP- of the average molecular weight of bigger I.Each in PVP-I ingredients is referred to herein as " high molecular weight PVP-I " or " HMW PVP-I ".
Another embodiment according to the composition of the subject innovation is stable topical otic's gel preparation (topical otic gel formulation), the topical otic includes about 0.1% to about 10% poly- dimension with gel preparation Ketone-iodine (PVP-I)；The dimethyl sulfoxide (DMSO) (DMSO) of about 30% to about 99%；The gelling agent of about 1% to about 10%；Wherein group Each ingredient closed in object is acceptable in otology, and be generally free of gelling agent and include about 0.1% to about 10% povidone-iodine is compared with the liquid composition of the DMSO of about 30% to about 99%, and ear gel combination is in treatment ear The effect of bigger being showed in the infection state of road and especially external ear or middle ear.
Preferred ear includes the PVP-I of about 0.25% to about 2.55% with gel combination.Preferred ear gel group The PVP-I that object includes about 1% to about 3% is closed, and most preferred ear includes about 1% PVP-I with gel combination.
The composition of the present invention preferably includes povidone-iodine or PVP-I with the average molecular weight more than 10,000. It is highly preferred that the composition of the present invention includes the PVP- with the average molecular weight between about 20,000 to about 1,000,000 I.One preferred embodiment includes high molecular weight (HMW) PVP-I.
Preferred ear includes the DMSO of about 30% to about 70% with gel combination.Preferred ear gel combination can To include the DMSO of about 40% to about 49%, and even more preferably about 44% DMSO.
Preferred ear includes the gelling agent of about 2% to about 5% with gel combination.Preferred ear gel combination can To include about 4% gelling agent.The particularly useful composition of infection for being prepared for treatment eyes or eyelid includes 1% PVP-I；44% DMSO；2% hydroxyethyl cellulose；With 53% aqueous solvent.Preferred aqueous solvent is water.
The present invention ear gel combination can include gelling agent well known in the art, the gelling agent be selected from natural gum, Agar, carrageenan, vaseline or cellulosic polymer or the like.A kind of preferred cellulose polymerization as gelling agent Object is hydroxyethyl cellulose (HEC).Selectable cellulosic polymer gelling agent is hydroxymethyl cellulose.In embodiments, Disclosed herein is the composition without steroids for treating otitis, the composition includes (the usually contracting of Iodophor such as povidone-iodine Be written as " PVP-I ") and dimethyl sulfoxide (DMSO) (being commonly abbreviated as " DMSO "), wherein the composition can permeate epithelialization duct or Eardrum can be permeated to treat external ear infection or middle ear infection.
In embodiments, disclosed herein for treat the composition of otitis to be generally anhydrous.In embodiment In, composition is anhydrous.
In embodiments, the composition disclosed herein for treating otitis includes with about 0.01% to about 10% (w/ W) PVP-I.In embodiments, PVP-I exists in the range of selected from the group being made up of：About 0.05% to about 10%, about 0.1% to about 5%, about 0.2% to about 2.5% and about 0.5% to about 1% (w/w).In embodiments, PVP- I exists in the range of selected from the group being made up of：About 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 1.0%, about 1.25%, about 1.5%, about 2.0%, about 2.5% and about 5% (w/w).In embodiments, PVP-I is with about 1% (w/w) exists.
In embodiments, the composition disclosed herein for treating otitis also includes at least one naturopathy substance (naturopathic substance).In embodiments, the composition disclosed herein for treating otitis also includes extremely A kind of few substance selected from the group being made up of：Punica granatum L. extract (Punica Granatum Extract), tea free extraction Object (Camellia Sinensis Leaf Extract), ascorbic acid, pot marigold extract (Calendula Officinalis Extract), glycyrrhiza glabra extract (Glycrrhiza Glabra Extract), allantoin and cucumber Berry extract (Cucumis Sativus Fruit Extract).
In embodiments, the composition disclosed herein for treating otitis also includes at least one selected from by with the following group At group antifungal agent：Tolnaftate, Terbinafine, undecenoic acid, clioquinol, Miconazole, miconazole nitrate, clotrimazole (clorrinazole), tioconazole, nystatin, terconazole, Butoconazole Nitrate, ciclopirox olamine, econazole nitrate, glyceryl triacetate, Flucytosine, Haloprogin and ketoconazole.In embodiments, antifungal agent is deposited with the amount of about 1% to about 25% (w/w) .
In embodiments, disclosed herein is the composition for treating otitis, the composition includes Iodophor such as PVP-I With dimethyl sulfoxide (DMSO) (DMSO), wherein the composition can permeate epithelialization duct or across eardrum come treat external ear infection or Middle ear infection, in addition wherein the composition does not include steroids, either " no steroids ".
In embodiments, this theme composition is formulated for local application, is configured to liquid auristilla preparation Or it is configured to gel.
In embodiments, composition of the invention includes a certain amount of gelling agent to be formed as the final combination of gel Object.In one embodiment, this theme composition is configured to topical gel.
Each of embodiment of compositions described herein is free of steroids, is the composition of no steroids.
Description embodiment and especially comprising in those of gelling agent embodiment, composition is formed for applying With the non-foaming topical compositions (non-foaming topical composition) to duct.Non- foaming topical compositions Foaming agent can be free of, or selectively when preparation includes the other compositions or excipient that can cause or cause blistering, Composition can include surfactant or other antifoaming agent, especially by comprising to assign not blistering property to disappearing for composition Infusion.Common agent be insoluble oil, dimethyl silicone polymer class and other organic silicons, certain alcohols, stearic acid esters and Glycols.Additive be used to prevent to be formed foam or be added to destroy the foam formed.
In embodiments, the infection treated is fungal infection.In embodiments, infection is dermatophyte infection (dermatophyte infection)。
In embodiments, the infection treated is bacterium ear infection.In embodiments, infection is selected from streptococcus sense Dye, staphy lococcus infection, acute Haemophilus influenzae infection and pseudomonas infection.
In embodiments, the infection treated is viral infection.In embodiments, infection is adenovirus infection.
In embodiments, the infection treated is amoeba infection.
In embodiments, disclosed herein is the method for treating otitis, the method includes to infected duct Using compositions disclosed herein, and contact procedure is repeated as needed, until otitis has been treated.In embodiment In, contact procedure is carried out at least one time daily.In embodiments, contact procedure is carried out at least twice daily.Special In surprising embodiment, the highly viscous gel preparation (greater than about 100,000cps viscosity) of even single dose is found The infection of the middle ear in children can be completely eliminated.
In embodiments, disclosed herein is the method for treating otitis, the method includes to infected duct Continue at least one week using the composition and repetitive administration step of claim 1.In embodiments, step of applying is weighed Continue at least two weeks again.In embodiments, step of applying, which is repeated, continues at least three weeks.In embodiments, step of applying It is repeated and continues at least surrounding.In embodiments, step of applying, which is repeated, continues up to 12 weeks.
This theme composition can be useful in the fungal infection in treating duct, wherein infecting by being selected from by following At least one of member of group of composition causes：Trichophyton rubrum (Trichophyton rubrum), Trichophyton mentagrophytes (T.mentagrophytes), acrothesium floccosum (Epidermophyton floccosum), trichophyton violaceum (T.violaceum), Microsporum gypseum (Microsporum gypseum), Trichophyton tonsurans (T.tonsurans), Soviet Union Red trichophyta (T.soudanense), Trichophyton verrucosum (T.verrucosum) and Mycotoruloides (Candida spp.), Neoscytalidium spp., scopulariopsis (Scopulariopsis spp.) and Eurotium (Aspergillus spp.) Member.
It is described in detail
The present invention relates to topical compositions, and preferably partially gel combination, the topical composition include Iodophor, infiltration Reinforcing agent and gelling agent in the case of gel combination, wherein the composition can cause otitis in treatment, usually especially It is or viral infection, Human Follicle Mite Infection, fungi/yeast infection, bacterium infection or the amoeba infection of otitis externa or tympanitis In be particularly effective.Therefore, the subject innovation further includes using topical composition as disclosed herein, preferably partially gel Composition treats the viral infection of duct, Human Follicle Mite Infection, fungi/yeast infection, bacterium infection or amoeba infection Method.The composition can also include pharmaceutically acceptable excipient optionally or solvent or cosolvent.
The composition of the subject innovation is preferably included by food and drug administration (United States Food And Drug Administration) (FDA) be recognized as in pharmaceutical preparation using being suitable and acceptable activity Drug ingedient (API).The preferred composition of the present invention also includes to be recognized as in medication for topical application product Using being suitable and acceptable non-active ingredient or excipient.The API or acceptable non-active ingredients of FDA approvals or tax Shape agent is referred to herein as " pharmaceutically acceptable ".Therefore, including pharmaceutically acceptable API, non-active ingredient or tax Topical composition, preparation or the product of the subject innovation of shape agent are referred to herein as " pharmaceutically acceptable " part combination Object.
Similarly, including in ear product using be acceptable FDA approval active constituent or it is nonactive at The ear for the subject innovation divided is referred to herein as " pharmaceutically acceptable ear composition " with composition or " can in otology Receive " composition, it includes be " pharmaceutically acceptable " or " in otology acceptable " API, tax for ear's use Shape agent or solvent.
More specifically, in preferred embodiments, subject invention relates to stable topical composition, stable parts Composition includes Iodophor, dimethyl sulfoxide (DMSO) (DMSO) and gelling agent and optional in addition acceptable pharmaceutically or in otology Excipient or solvent or cosolvent, the Iodophor have the molecular weight more than 10,000 dalton.
Any combinations of the one kind or at least two of the composition and method in treating the above disease, situation or pathogen In be useful.
In embodiments, composition includes at least one therapeutic agent and at least one solvent and/or bleeding agent to composition. In one aspect, Iodophor is therapeutic agent.In embodiments, composition includes at least one preservative compounds.On the one hand In, preservative compounds are therapeutic agents.In embodiments, composition includes Iodophor preservative." Iodophor " as used herein Refer to comprising iodine and when in the solution at least one other agent (such as solubilizer) of release free-iodine substance.Iodophor Example include but not limited to povidone iodine (PVP-I), the tincture of iodine (iodine tincture), Lugol's Solution and salt compounded of iodine (example Such as potassium iodide, sodium iodide).
In embodiments, composition includes at least one Iodophor.Composition includes any Iodophor and needs out so far Hair or the Iodophor found.In embodiments, Iodophor is PVP-I.In another embodiment, composition includes iodine.In reality It applies in scheme, composition includes iodine and at least one Iodophor.
In embodiments, PVP-I plays therapeutic agent in the composition.In one aspect, PVP-I therapeutic agents rise anti- The effect of rotten agent.In another embodiment, PVP-I plays preservative agent (preservative) in the composition. In one side, PVP-I preservative agents play preservative.In another aspect, PVP-I preservative agents play stabilizer. In embodiment, PVP-I is worked at least one times of capacity in the composition.In another embodiment, PVP-I is being combined It is worked at least twice capacity in object.
In another embodiment, composition also includes at least one non-Iodophor, non-iodine therapeutic agent.In embodiment In, at least one non-Iodophor, non-iodine therapeutic agent are preservatives.In another embodiment, at least one non-Iodophor, non-iodine are controlled It is not preservative to treat agent.
In embodiments, at least one non-Iodophor, non-iodine therapeutic agent are antifungal agents.Suitable antifungal agent includes example Such as propylamine and azole.In embodiments, antifungal agent include but not limited to Tolnaftate, Terbinafine, undecenoic acid, Clioquinol, Miconazole, miconazole nitrate, clotrimazole, tioconazole, nystatin, terconazole, Butoconazole Nitrate, ciclopirox olamine, Econazole nitrate, glyceryl triacetate, Flucytosine, Haloprogin and ketoconazole.
In embodiments, composition includes one or more of naturopathy substances.Naturopathy substance includes but not It is limited to pomegranate (Punica Granatum) (pomegranate (Pomegranate)) extract, tea free (green tea (Green Tea)) carries Take object, ascorbic acid (vitamin-C), pot marigold extract, glycyrrhiza glabra (Radix Glycyrrhizae (Licorice)) extract, allantoin with And cucumber (Cucumis Sativus) (cucumber (Cucumber)) berry extract.In embodiments, composition include DMSO, It is PVP-I, pomegranate (Punica Granatum) (pomegranate (Pomegranate)) extract, tea free (green tea) extract, anti-bad Hematic acid (vitamin-C), pot marigold extract, glycyrrhiza glabra (Radix Glycyrrhizae (Licorice)) extract, allantoin and cucumber (Cucumis Sativus) (cucumber (Cucumber)) berry extract.
In embodiments, composition includes at least one solvent and/or bleeding agent.In embodiments, one pack system can To play both solvent and bleeding agent in the composition.In embodiments, composition includes DMSO.In one aspect, DMSO plays the bleeding agent of active component.In one aspect, DMSO plays solvent.In another aspect, DMSO rises The effect of both solvent and bleeding agent.In embodiments, DMSO is unique bleeding agent in composition.In embodiment In, DMSO is unique solvent in composition.In embodiments, DMSO is unique bleeding agent in composition and molten Agent.
In embodiments, composition includes PVP-I and DMSO.In another embodiment, composition by PVP-I and DMSO is formed.In yet another embodiment, composition is substantially made of PVP-I and DMSO.
Those skilled in the art will understand the composition for how determining and can be used for being covered herein based on disclosure With the bleeding agent of method.In embodiments, bleeding agent is the infiltration that can be used for enabling composition to permeate onyx (unguis) Agent.By way of non-limiting example, methyl sulfonyl methane is used as such as the infiltration in the composition covered herein Agent.
In embodiments, composition includes at least one cosolvent.In embodiments, composition includes molten as master The DMSO of agent (primary solvent), and also include at least one cosolvent.In embodiments, water is cosolvent. In embodiment, composition includes the DMSO as main solvent and the water as cosolvent.In embodiments, composition is by making DMSO for main solvent and the water composition as cosolvent.In another embodiment, composition is substantially by molten as master The DMSO of agent and as cosolvent water form.In embodiments, composition includes at least one cosolvent, such as but unlimited In water or ethyl alcohol.In embodiments, cosolvent is one or more of polar non-solutes.In embodiments, molten altogether Agent is ethyl acetate.In embodiments, cosolvent is at least one of the following：Ethyl acetate, acetone, acetonitrile, tetrahydrochysene furan It mutters, dichloromethane and dimethylformamide.In view of the disclosure stated herein, those skilled in the art will be based on such The property of possible cosolvent and physical action understand using the advantages of cosolvent and limitation.
In embodiments, composition includes at least one excipient, such as, but not limited to sodium chloride, sodium dihydrogen phosphate one Hydrate, Anhydrous Disodium Phosphate and water.The composition covered herein will be understood as optionally including people in the art Other one or more of excipient known to member.Skilled artisan would know how such excipient is determined as at this It is useful in inventive composition and method, such as when such excipient enhances treatment effect, the stability of composition or method Or when validity.
Dosage, form and preparation
In embodiments, composition includes at least one therapeutic agent of therapeutically effective amount.Unless otherwise instructed, otherwise originally Text describes the compound for being used to or realizing the treatment results being intended within a context using term " therapeutically effective amount " Amount.In embodiments, it is intended that treatment results be related to the treatment of onychomycosis.In embodiments, therapeutically effective amount is It is enough to treat the amount of otitis, and the treatment of otitis includes the progress for preventing or slowing down infection, prevents the sprawling infected, eliminates extremely Few certain infection and elimination all at least one of infection.In one aspect, therapeutically effective amount can based on single dose come It determines or therapeutically effective amount can be determined based on the composition of multi-dose.It will be appreciated that determining that therapeutically effective amount may Repetition test is needed, and regulating dosage and/or dosage regimen may be needed.Such treatment optimization and adjusting are covered herein Method covered.
Such as refer to increase or carrying herein in regard to the term " pharmaceutically acceptable " that compound or composition uses Solubility of the high compound in subject or availability are to promote or improve the bioavilability of compound or composition The form of compound or composition.In one aspect, this disclosure is also contemplated by the compound embodied herein and combination Pharmaceutically acceptable hydrate, solvate, stereoisomer or the amorphous solid of object.
As used herein, " pharmaceutically acceptable carrier " include any and all solvent, decentralized medium, coating, Surfactant, antioxidant, preservative agent (such as antibacterial agent, antifungal agent), isotonic agent, absorption delaying agent, salt, preservation It is agent, drug, drug stabilizing agent, gel, adhesive, excipient, disintegrant, lubricant, sweetener, flavoring agent, dyestuff, such Similar material and combinations thereof, such as will be to known to persons of ordinary skill in the art (see, for example, Remington's Pharmaceutical Sciences, 1990, be incorporated herein by reference).Unless any conventional carrier and active constituent or Application method is incompatible, otherwise uses it for being expected in pharmaceutical composition.
Unless otherwise instructed, the percentage otherwise stated herein is relative to specified ingredients in total composition (w/w).Example Such as, including the composition of the DMSO of 1% PVP-1 and 99% has by weight 1% PVP-I relative to total composition.
In embodiments, composition is included in the Iodophor in the range of about 0.01% to about 15%.In another implementation In scheme, composition is included in the Iodophor between 0.05% and 12.5%.In another embodiment, composition Iodophor between 0.05% and 10.0%.In another embodiment, composition is included in 0.1% He Iodophor between 10.0%.In another embodiment, composition is included in the model between 0.1% and 5.0% Enclose interior Iodophor.In another embodiment, composition is included in the Iodophor between 0.25% and 9.0%. In another embodiment, composition is included in the Iodophor between 0.2% and 2.5%.In another embodiment In, composition is included in the Iodophor between 0.5% and 7.5%.In another embodiment, composition is included in Iodophor between 0.5% and 1.0%.In another embodiment, composition be included in 0.75% and 5.0% it Between in the range of Iodophor, and the Iodophor between 1.0% and 4.0% in yet another embodiment.In reality It applies in scheme, composition is included in about 0.1% to about 2.5%, about 0.2% to about 2.0%, about 0.3% to about 1.0% and about Iodophor in the range of 0.4% to about 0.75%.
In embodiments, composition is included in the elemental iodine in the range of about 0.01% to about 15%.In another reality It applies in scheme, composition is included in the elemental iodine between 0.05% and 12.5%.In another embodiment, group Close the elemental iodine that object is included between 0.05% and 10.0%.In another embodiment, composition is included in Elemental iodine between 0.1% and 10.0%.In another embodiment, composition is included in 0.1% and 5.0% Between elemental iodine.In another embodiment, composition is included between 0.25% and 9.0% Elemental iodine.In another embodiment, composition is included in the elemental iodine between 0.2% and 2.5%.Another In one embodiment, composition is included in the elemental iodine between 0.5% and 7.5%.In another embodiment In, composition is included in the elemental iodine between 0.5% and 1.0%.In another embodiment, composition includes Elemental iodine between 0.75% and 5.0%, and in yet another embodiment between 1.0% and 4.0% In the range of elemental iodine.In embodiments, composition be included in about 0.1% to about 2.5%, about 0.2% to about 2.0%, Elemental iodine in the range of about 0.3% to about 1.0% and about 0.4% to about 0.75%.
In embodiments, composition is included in the PVP-I in the range of about 0.01% to about 15%.In another implementation In scheme, composition is included in the PVP-I between 0.05% and 12.5%.In another embodiment, it combines Object is included in the PVP-I between 0.05% and 10.0%.In another embodiment, composition is included in PVP-I between 0.1% and 10.0%.In another embodiment, composition is included in 0.1% and 5.0% Between PVP-I.In another embodiment, composition is included between 0.25% and 9.0% PVP-I.In another embodiment, composition is included in the PVP-I between 0.2% and 2.5%.Another In a embodiment, composition is included in the PVP-I between 0.5% and 7.5%.In another embodiment, Composition is included in the PVP-I between 0.5% and 1.0%.In another embodiment, composition is included in PVP-I between 0.75% and 5.0%, and the model between 1.0% and 4.0% in yet another embodiment Enclose interior PVP-I.In embodiments, composition be included in about 0.1% to about 2.5%, about 0.2% to about 2.0%, about PVP-I in the range of 0.3% to about 1.0% and about 0.4% to about 0.75%.
In embodiments, composition include with about 0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.25%, about 1.50%, about 1.75%, about 2.0%, about 2.5%, about 5%, about 7.5%, about 10%, about 12.5, Or about 15.0% PVP-I.In embodiments, composition include with 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.25%, 1.5%, 1.75%, 2.0%, 2.25%, 2.5%, 5%, 7.5%, 10.0%, 12.5% or 15% PVP-I.In another embodiment party In case, composition includes with about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10% PVP-I.In another embodiment, composition includes with about 0.1% or smaller, about 0.5% or smaller, about 1% or more It is small, about 2% or smaller, about 3% or smaller, about 4% or smaller, about 5% or smaller, about 6% or smaller, about 7% or smaller, about 8% or smaller, about 9% or smaller or about 10% or smaller PVP-I.In another embodiment, composition includes with about 0.01% or bigger, about 0.05% or bigger, about 0.075% or bigger, about 0.1% or bigger, about 0.2% or bigger, about 0.3% or bigger, about 0.4% or bigger, about 0.5% or bigger, about 0.6% or bigger, about 0.7% or bigger, about 0.8% or Bigger, about 0.9% or bigger, about 1% or bigger, about 2% or bigger, about 3% or bigger, about 4% or bigger, about 5% or more Greatly, about 6% bigger, about 7% or bigger, about 8% or bigger, about 9% or bigger or about 10% or bigger PVP-I.Another In one embodiment, composition include with 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0% or 10.0% PVP-I.
In embodiments, composition includes DMSO and PVP-I.In embodiments, composition substantially by DMSO and PVP-I is formed.In embodiments, composition is made of DMSO and PVP-I.In embodiments, composition is anhydrous. In embodiment, composition is generally anhydrous.In embodiments, composition includes the water of measurable amount.
In embodiments, anhydrous DMSO is used in the composition.In embodiments, it uses in the composition substantially Upper anhydrous DMSO.It will be understood by those skilled in the art that can be produced with different brackets and/or obtain DMSO, and in difference One in variable in the DMSO products of grade is water content.By way of example, DMSO can be completely it is anhydrous ( Also be called for short herein " anhydrous "), water generally anhydrous or that measurable degree can be included.It will be appreciated that The amount of measurable water can be based on changing for carrying out the limitation of such instrument measured and technology in DMSO products. In embodiment, not being complete anhydrous DMSO can be generally anhydrous and include with the level less than detectable level Water.In embodiments, be not complete anhydrous DMSO can include water, wherein water content is about at least 0.01%, about extremely Few 0.02%, about at least 0.03%, about at least 0.04%, about at least 0.05%, about at least 0.06%, about at least 0.07%, about At least 0.08%, about at least 0.09%, about at least 0.1%, about at least 0.2%, about at least 0.3%, about at least 0.4%, about extremely Few 0.5%, about at least 0.6%, about at least 0.7%, about at least 0.8%, about at least 0.9%, about at least 1.0%, about at least 1.5%, about at least 2.0%, about at least 2.5%, about at least 5%, about at least 7.5%, about at least 10%, about at least 12.5%, Or bigger.In embodiments, be not complete anhydrous DMSO can include water, wherein water content is to be approximately less than 0.01%, about Less than 0.02%, be approximately less than 0.03%, be approximately less than 0.04%, being approximately less than 0.05%, being approximately less than 0.06%, being approximately less than 0.07%, It is approximately less than 0.08%, is approximately less than 0.09%, is approximately less than 0.1%, is approximately less than 0.2%, is approximately less than 0.3%, is approximately less than 0.4%, about Less than 0.5%, it is approximately less than 0.6%, is approximately less than 0.7%, is approximately less than 0.8%, is approximately less than 0.9%, is approximately less than 1.0%, is approximately less than 1.5%, be approximately less than 2.0%, be approximately less than 2.5%, being approximately less than 5%, being approximately less than 7.5%, being approximately less than 10%, being approximately less than 12.5%, Or bigger.It will be appreciated that in addition to water, DMSO can also include one or more of other impurities.
In embodiments, composition includes Iodophor, bleeding agent, and also includes water.In embodiments, composition packet Containing anhydrous Iodophor and/or anhydrous bleeding agent, and also include water.In embodiments, composition includes PVP-I, DMSO, and Also include water.In embodiments, composition includes Iodophor and bleeding agent, and includes also water, and wherein water content is about at least 0.01%, about at least 0.02%, about at least 0.03%, about at least 0.04%, about at least 0.05%, about at least 0.06%, about extremely Few 0.07%, about at least 0.08%, about at least 0.09%, about at least 0.1%, about at least 0.2%, about at least 0.3%, about at least 0.4%, about at least 0.5%, about at least 0.6%, about at least 0.7%, about at least 0.8%, about at least 0.9%, about at least 1.0%, about at least 1.5%, about at least 2.0%, about at least 2.5%, about at least 5%, about at least 7.5%, about at least 10%, about At least 12.5% or bigger.In embodiments, composition includes Iodophor and bleeding agent, and also includes water, wherein water content It is to be approximately less than 0.01%, be approximately less than 0.02%, be approximately less than 0.03%, be approximately less than 0.04%, be approximately less than 0.05%, be approximately less than 0.06%, it is approximately less than 0.07%, 0.08% is approximately less than, is approximately less than 0.09%, is approximately less than 0.1%, is approximately less than 0.2%, is approximately less than 0.3%, it is approximately less than 0.4%, 0.5% is approximately less than, is approximately less than 0.6%, is approximately less than 0.7%, is approximately less than 0.8%, is approximately less than 0.9%, be approximately less than 1.0%, be approximately less than 1.5%, being approximately less than 2.0%, being approximately less than 2.5%, being approximately less than 5%, being approximately less than 7.5%, It is approximately less than 10%, is approximately less than 12.5% or bigger.In embodiments, composition includes Iodophor and bleeding agent, and also includes Water, wherein water content is about 0.01% to about 12.5%, about 0.02% to about 10.0%, about 0.03% to about 7.5%, about 0.04% to about 5%, about 0.05% to about 2.5%, about 0.06% to about 2%, about 0.07% to about 1.5%, about 0.08% to About 1%, about 0.09% to about 0.9%, about 0.1% to about 0.8% or about 0.2% to about 0.7%.In one aspect, water can be with From the component of composition.In another aspect, water can be specifically added to composition.
In embodiments, composition includes the United States Pharmacopeia committee (United States Pharmacopeia Convention) (USP) grade DMSO, active pharmaceutical ingredient (API) grade DMSO, analysis level DMSO and American Chemical Society (ACS) At least one of order of spectrum DMSO.In embodiments, composition includes and has to titrate by KF<0.1% water and It determines on the anhydrous basis>99.9% DMSO.
As set forth above, unless otherwise stated, the percentages of DMSO in the composition are with relative to combination The weight-of one or more of other components in object is described with-weight (w/w) ratio.In embodiments, the weight of DMSO Amount percentage is the surplus of the weight percent after adding PVP-I.By way of non-limiting example, composition can wrap The DMSO of PVP-1 and 99 weight percent (99%) containing 1 weight percent (1%).It will be appreciated that in previous examples, The DMSO components of composition can be water that is completely anhydrous, generally anhydrous or can including measurable degree.Implementing In scheme, the weight percent of DMSO is to add PVP-I and any other component (for example, cosolvent, water, activity in addition Ingredient etc.) after weight percent surplus.In embodiments, the weight percent of DMSO is in addition Iodophor and other The surplus of weight percent after component (if any).In embodiments, the weight hundred of the bleeding agent in composition It is the surplus of the weight percent after addition Iodophor and other components (if any) to divide ratio.
In embodiments, composition is included in the DMSO in the range of 50% to 99.99%.In embodiments, group Close the DMSO that object is included in the range of 1% to 99.99%.In another embodiment, composition is included in 5% He DMSO in the range of 99.9%.In another embodiment, composition is included in the range of 10% and 99.9% DMSO.In another embodiment, composition is included in the DMSO in the range of 20% and 99.9%.In another embodiment party In case, composition is included in the DMSO in the range of 30% and 99.9%.In another embodiment, composition is included in DMSO in the range of 40% and 99.9%.In another embodiment, composition is included in 50% and 99.9% range Interior DMSO.In another embodiment, composition is included in the DMSO in the range of 60% and 99.9%.In another reality It applies in scheme, composition is included in the DMSO in the range of 70% and 99.9%.In another embodiment, composition includes DMSO in the range of 80% and 99.9%, and the DMSO between 90% and 99.9% in yet another embodiment. In embodiments, composition includes with the DMSO of weight percent below：About at least 80%, about at least 85%, about at least 87.5%, about at least 90%, about at least 91%, about at least 92%, about at least 93%, about at least 94%, about at least 95%, about extremely Few 96%, about at least 97%, about at least 98%, about at least 99% or about at least 99.9%.
In embodiments, composition includes DMSO but does not include any other solvent (such as cosolvent) or infiltration Agent.In another embodiment, composition is included in the DMSO in the range of about 0.01% to 99.99%, and also includes At least one cosolvent in the range of 0.01% to about 99.99%.In embodiments, composition includes DMSO, and At least one cosolvent being also included in the range of about 0.1% to about 50%.
In another embodiment, composition includes DMSO, and the range being also included between about 5% and about 50% Interior at least one cosolvent.In another embodiment, composition includes DMSO, and is also included in about 10% peace treaty At least one cosolvent between 99%.In another embodiment, composition includes DMSO, and also includes At least one cosolvent between about 20% and about 95%.In embodiments, composition includes DMSO, and Also it is included in about 50% to about 60%, about 60% to about 80%, about 70% to about 90% and the range of about 80% to about 95% Interior at least one cosolvent.In one aspect, water is cosolvent.In embodiments, composition includes DMSO, water and at least A kind of other cosolvent.
In embodiments, composition is included in the DMSO in the range of about 0.01% to 99.99%, and is also included in At least one bleeding agent in the range of 0.01% to about 99.99%.In embodiments, composition includes DMSO, and also At least one bleeding agent in the range of about 0.1% to about 50%.In another embodiment, composition includes DMSO, and also it is included at least one bleeding agent between about 5% and about 50%.In another embodiment In, composition includes DMSO, and is also included at least one bleeding agent between about 10% and about 99%.In reality It applies in scheme, composition includes DMSO, at least one cosolvent and at least one bleeding agent.In embodiments, cosolvent It is bleeding agent.
In embodiments, composition is included in the gelling agent in the range of about 0.01% to about 10%.In another reality It applies in scheme, composition is included in the gelling agent between 0.05% and 7.5%.In another embodiment, group Close the gelling agent that object is included between 0.1% and 5.0%.In another embodiment, composition is included in Gelling agent between 0.25% and 4.5%.In another embodiment, composition is included in 0.5% and 4.0% Between gelling agent.In another embodiment, composition is included between 1.0% and 3.0% Gelling agent.In another embodiment, if it is desired to higher viscosity, composition include with about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0% or bigger Amount gelling agent.The preferred embodiment of composition includes the gelling agent less than 10%.
In embodiments, composition includes at least one antifungal agent selected from the group being made up of：Tolnaftate, spy Than naphthalene sweet smell, undecenoic acid, clioquinol, Miconazole, miconazole nitrate, clotrimazole, tioconazole, nystatin, terconazole, nitre Sour butoconazole, ciclopirox olamine, econazole nitrate, glyceryl triacetate, Flucytosine, Haloprogin and ketoconazole.In embodiments, At least one antifungal agent with about 0.01%, about 0.05%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, About 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.25%, about 1.50%, about 1.75%, about 2.0%, about 2.5%, about 5%, about 7.5%, about 10%, about 12.5%, about 15.0%, about 20%, about 25%, about 30%, about 40% or about 50% exists.In embodiments, composition include 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.25%, 1.5%, 1.75%, 2.0%, 2.25%, 2.5%, 5%, 7.5%, 10.0%, 12.5%, 15%, 20%, 25%, 30%, 40% or 50% at least one antifungal agent.Another In a embodiment, composition includes about 0.1% or smaller, about 0.5% or smaller, about 1% or smaller, about 2% or smaller, about 3% or smaller, about 4% or smaller, about 5% or smaller, about 6% or smaller, about 7% or smaller, about 8% or smaller, about 9% or Smaller, about 10% or smaller, about 20% or smaller, about 25% or smaller, about 30% or smaller, about 40% or smaller or about 50% or smaller at least one antifungal agent.In another embodiment, composition includes about 0.1% or bigger, about 0.5% or bigger, about 1% or bigger, about 2% or bigger, about 3% or bigger, about 4% or bigger, about 5% or bigger, about 6% Or bigger, about 7% or bigger, about 8% or bigger, about 9% or bigger, about 10% or bigger, about 20% or bigger, about 25% or Bigger, about 30% or bigger, about 40% or bigger or about 50% or bigger at least one antifungal agent.In another implementation In scheme, composition include 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 20%, 25%, 30%, 40% or 50% at least one antifungal agent.
In embodiments, at least one topical anti-fungal ingredient known in the art (passes through the side of non-limiting examples Formula include 1% Tolnaftate, 10%-25% undecenoic acids, clioquinol 3% and/or miconazole nitrate 2%) stabilization system Product can be prepared in DMSO dicyandiamide solutions, and wherein PVP-I is also incorporated into as long-term preservation agent.These solution are shown significantly Long-time stability, wherein PVP-I components and antimycotic component can both be maintained at or higher than the 90% of initial concentration. It was surprisingly found that not having significantly to react between antifungal agent and PVP-I.These preparations are also shown as anti- The significant in vitro and in vivo effect of epiphyte pharmaceutical.
In embodiments, in the conceived case, composition may be embodied in the compound in composition pharmaceutically Acceptable salt.In embodiments, composition includes the acid-addition salts (acid addition salt) of the compounds of this invention. In embodiments, composition includes the base addition salts (base addition salt) of the compounds of this invention.As used herein , term pharmaceutically acceptable salt or complex compound are referred to retaining the desired bioactivity of parent compound and be showed The salt or complex compound (such as solvate, polymorph) of minimum (if any) undesirable toxicological effect.
In composition for topical application, mixture is preferably formulated as the aqueous solution in the pH of 2.0-6.5.It is excellent PH is adjusted between 2.5 and 4.5 by selection of land.This pH range can be by the composition comprising suitable acid/base come real It is existing.
In one aspect, composition can include excipient, antimicrobial, preservative agent, cosolvent, surfactant, One or more in viscosity agent and/or bioadhesive, as the other places this paper are stated in detail.
In one aspect, pharmaceutical preparation is part containing alcohol product (partially-alcoholic preparation).Such as It will appreciated by a person of ordinary skill in the art taht the alcohol comprising certain percentage will be helpful to the solubility of component in product, described group It includes PVP-I to divide.Alkoxide component also will act as the dehydration component on the surface that product is applied to.Alcohol for use in the present invention includes first Alcohol, ethyl alcohol and isopropanol and other.
Lubricant
In embodiments, composition may include one or more of lubricants, including but not limited to propylene glycol, glycerine, Polyethylene glycol, dextran, blended polyethylene alcohols, polyvinyl alcohol, polyethylene glycol, light mineral oil, hydroxypropyl methyl fiber Element, hydroxypropyl methylcellulose, carbopol, Acritamer 940 (polyacrylic acid), polyvinylpyrrolidone, albolene, soybean lecithin And sodium carboxymethylcellulose and other agent well known by persons skilled in the art or any combination thereof.In general, this series lubricant agent with Level by weight from 0.1% to 2% uses.In embodiments, lubricant be 1.0% propylene glycol, 0.3% glycerine, 2.7% blended polyethylene alcohols, 1% polyvinyl alcohol, 1% polyethylene glycol, light mineral oil, 0.3% hydroxypropyl methyl cellulose, The sodium carboxymethylcellulose of 1.0% soybean lecithin, 0.25% or 0.5%.In another embodiment, PVP-I, based on artificial The total weight of the lubricant (artificial-tear based lubricant) of tear is between 0.1% and 4.5%.
Other antimicrobial and antibiotic
Suitable antibiotics/antimicrobials include but not limited to fluoroquinolones (Ciprofloxacin, lavo-ofloxacin, oxygen Flucloxacillin, Moxifloxacin (moxifloxacin), gatifloxacin (gatifloxacin) and the like)；Aminoglycoside (appropriate cloth Mycin, gentamicin, neomycin and the like)；(Polymyxin B sulfate/trimethoprim, Polysporin are mostly glutinous for Polymyxin B sulfate combination Rhzomorph B/ bacitracins, Neosporin Polymyxin B sulfates/neomycin/gramicidins and the like) and other antibiotic (Archies Mycin, erythromycin (ilotycin), erythromycin (erythromycin), bacitracin and the like).
Local anesthetic
Suitable local anesthetic for the compositions and methods of the invention includes but not limited to lidocaine, totokaine Or derivatives thereof or combination.
Antiallergy component
Antiallergy component includes but not limited to epinastine, emedastine difumarate, hydrochloric acid nitrogenSting, hydrochloric acid Ao Luota Fixed (olopatadine hydrochloride), olopatadine, Ketotifen Fumarate, pemirolast potassium, nedocromil, Lip river degree Husky amine, Cromoglycic acid and cromoglycate and zinc acetate.
Preservative agent
Preservative agent includes benzalkonium chloride, thimerosal, methaform, methyl hydroxybenzoate, Nipasol, benzyl carbinol, EDTA, sorb Acid, Onamer M, other agent well known by persons skilled in the art or combinations thereof.In general, such preservative agent is with final composition Level by weight from 0.001% to 1.0% uses.
Cosolvent
The composition of the present invention can include one or more of optional cosolvent.The component of the present composition it is molten Solution degree can be improved by surfactant in composition or other suitable cosolvent.Such cosolvent/surface-active Agent includes polysorbate20, polysorbate60 and polysorbate80, polyoxyethylene/polyoxypropylene surfactant (example Such as Pluronic F-68, Pluronic F-84 and Pluronic P-103), cyclodextrin, tyloxapol, those skilled in the art Other known agent or combinations thereof.In general, such cosolvent with final composition by weight from 0.01% to 2% level It uses.
It releives agent (Soothing Agent)
In addition, when PVP-I solution is applied to ear, composition can include a effective amount of chemical agent, cool to provide Refreshing to feel (cooling sensation) to mitigate mild ear's stimulation, enhancing is comfortable, provides refresh oneself (refreshing) Effect and improved feeling.Such dose covers multi-chemical and chemical classes, including but not limited to coolant (cooling Agent) such as menthol, menthol derivative (including menthone glycerin acetonyl ester and menthyl ester), benzamide type, terpane are sweet Oily ketal class, alkyl-substituted ureas, sulfonamides, terpene analog, Furanones and phosphinoxides；Or camphor and borneol.
Viscosity agent
The composition of the present invention can include optional viscosity agent-i.e., it is possible to increase the agent of viscosity.It is increased above simple Aqueous solution viscosity viscosity can be it is desirable, with increase reactive compound ear absorb, reduce allotment preparation can Denaturation, reduces the physical separation of the suspension of preparation or the component of lotion and/or improves aural preparations in another way.It is such Tackifier (viscosity builder agents) include polyvinyl alcohol, polyvinylpyrrolidone, the methyl fibre as example Tie up element, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, those skilled in the art Other agent known or combinations thereof.In general, such dose is used with the level by weight from 0.01% to 2% of final composition.
Bioadhesive
Bioadhesive can be used to increase in the composition the retention time of the drug gradient on bio-matrix.Biology Adhesive can include but is not limited to：Polyvinylpyrrolidone (PVP), xanthans, locust bean gum, acacin, hydroxypropyl first Base cellulose (HPMC), sodium alginate, pectin, gelatin, carbomer, polyvinyl alcohol, gellan gum, bassora gum, Arabic gum and Sodium carboxymethylcellulose.
The assessment of preparation and validity
In embodiments, method and composition of the invention can reduce the progress of infective otitis externa so that not have Detect other progress.It may use any method come whether the progression rates of the severity or otitis externa that determine symptom subtract It is small.For example, the mankind with otitis externa can be inquired about pain before and after treatment and uncomfortable, to determine external ear Whether scorching symptom (such as otalgia or ear itching) mitigates.In some cases, mammal can be observed or test with according to this The severity of the symptom of otitis externa before and after the composition treatment of invention is (for example, ear discharge (ear Discharge), ear reduces the susceptibility or hearing of touch on susceptibility, the ear-lobe of pressure), to determine the serious journey of symptom Whether degree mitigates.In some cases, ENT doctor can assess the serious journey of otitis externa before and after treatment It spends (for example, by carrying out a medical examination and specifying 1 grade to 4 grades score, these characteristics are known in the art), to determine disease Whether the severity of shape mitigates.In order to determine whether the progress of otitis externa reduces, carry out physique can be put in different times It checks to determine the amount of erythema and/or oedema in duct and around duct.What can be observed more in different time points is red The amount of spot and oedema is to assess progression rates.After treatment as described herein, another time interval can be again passed by Progression rates are determined to determine whether progression rates are decreased.
Therefore, it will be understood that the effective quantity of the composition of the subject innovation comprising PVP-I and DMSO is to reduce symptom Any amount of the progress of severity or otitis externa without generating apparent toxicity to mammal.For example, in ear drops system In agent, a effective amount of PVP-I can be povidone-iodine from about 0.1% to about 10% (for example, about 2%).In embodiments, Including the effective quantity of the composition of PVP-I and DMSO can be from about 2 drop to about 8 drop be applied to ear include about 1%- 2% povidone-iodine and about 30% or bigger DMSO ear drops preparation.
If mammal does not show response to the composition of the present invention of specific quantity, such as can increase One or more of amounts in PVP-I and DMSO.After receiving this higher concentration, mammal can be monitored to treatment and poison The response of both property symptoms, and correspondingly make adjusting.Effective quantity can keep constant or can be adjusted to increase in proportion The dosage that subtracts or can be changed depends on response of the mammal to treatment.Many factors can influence the reality for specific application Effective quantity.For example, frequency of administration, duration for the treatment of, the use of a variety of therapeutic agents, administration method, the immunity energy of mammal The severity of power and otitis externa may need increaseing or decreasing for the actually active amount applied.Frequency of administration can be reduced Any frequency of the severity or progression rates of the symptom of otitis externa without generating apparent toxicity to mammal.For example, Frequency of administration can be from about once a day to about four times a day (for example, about twice daily).Frequency of administration treatment it is lasting when Between during can keep constant or can be variable.
In another aspect, the process treated with the composition of the subject innovation may include rest period (rest period).For example, composition can be administered within one week or two weeks time, it is followed by the rest period of one week or two weeks, and And such scheme can be repeated quickly and easily as many times as required.As effective quantity, many factors can influence actually applying for specific application Use frequency.For example, effective quantity, duration for the treatment of, the use of a variety of therapeutic agents, administration method, the immunocompetence of mammal And the severity of otitis externa may need increaseing or decreasing for frequency of administration.For having for application composition provided herein Severity or the progression rates for imitating the symptom that the duration can be reduction otitis externa are apparent without being generated to mammal Any duration of toxicity.Therefore, the effective duration can change from a few days to a few weeks, several months or several years.In general, Effective duration for treating otitis externa can be in from several days to the duration in several weeks range.In certain situations Under, effective duration can continue, as long as individual mammal is living.Many factors can be influenced for particular treatment The actually active duration.For example, effectively the duration can with frequency of administration, effective quantity, a variety of therapeutic agents use, apply Changed with approach, the severity of the immunocompetence of mammal and otitis externa.
Diagnosing and treating Consideration above can be applied to the treatment of tympanitis and otitis externa in a similar way.
Preparation method and application method
Pair it is known to those skilled in the art that PVP-I aqueous solutions be difficult in long period it is steady in low PVP-I concentration It is fixed.By non-limiting examples, in the concentration of the PVP-I less than about 0.7% (w/w, aqueous), PVP-I aqueous solutions divide rapidly It solves (decay), to generate iodate ingredient and the complex mixture without iodine ingredient.As described herein, it has therefore been surprisingly found that In the non-proton DMSO dicyandiamide solutions covered by the disclosure stated herein, the PVP-I solution down to 0.1% can be easy Ground is produced and keeps section for a long time as stable composition.In addition as described herein, prepared by aqueous PVP-I Hydration DMSO solution show increased stability, which is noted due to PVP-I components.
In embodiments, composition includes doing in the composition for being dissolved or suspended in comprising DMSO or being made of DMSO Dry, solid or powdered PVP-I.In another embodiment, DMSO is added into comprising PVP-I or by PVP-I Composition contains aquatic product.Based on this disclosure, it will be appreciated by those skilled in the art that how to prepare composition with reach iodine, The desired amount of other possible components of Iodophor and DMSO and the composition covered herein.
By way of non-limiting example, had to prepare treatment using the solid PVP-I being dissolved or suspended in DMSO The pharmaceutical composition of effect.In one aspect, composition is anhydrous.In one aspect, composition is generally anhydrous.Another In one embodiment, DMSO can be added to the aqueous solution of PVP-I to prepare treatment drug composition effective.Implementing In scheme, as the cosolvent with water, DMSO in the range of 50%-99% to be used.In embodiments, preparation includes One or more of excipient.By way of non-limiting example, excipient includes but not limited to sodium chloride, sodium dihydrogen phosphate Monohydrate, Anhydrous Disodium Phosphate and water and other excipient well known by persons skilled in the art.
In embodiments, composition is made by the way that 10%PVP-I (w/v, aqueous) is added to suitable pure DMSO It is standby, to obtain the acquired solution of 1% PVP-I (w/w) and DMSO.In another embodiment, composition is by by solid PVP-I is dissolved in be prepared in suitable pure DMSO, with obtain 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1.0%, 1.25%, 1.5%, 2.0% or 2.5%PVP-I (w/w), and about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, any in about 1.0%, about 1.25%, about 1.5%, about 2.0% or about 2.5%PVP-I (w/w) composition, wherein DMSO is as solvent.In yet another embodiment, composition is made by the way that solid PVP-I to be dissolved in suitable pure DMSO It is standby, to obtain any composition that is set forth herein, describing and/or cover.Including aqueous PVP-I is (with and without this Common and/or known excipient in field) similar composition with DMSO can from 10% PVP-I aqueous stock solutions It is prepared with pure DMSO.However, the skilled person will understand that, when progress dilution appropriate and adjust to generate desired final PVP- When I concentration, any starting composition of the PVP-I of solid or liquid can be used.Similarly, when progress dilution appropriate and tune When section to generate desired final Iodophor concentration or element iodine concentration respectively, any initial set of Iodophor or elemental iodine can be used Close object.
In embodiments, the case where otitis, is especially useful that, the PVP-I being included between 0.01%-10% The anhydrous composition of stabilization can be prepared in pure USP grades of DMSO solvent.
Will be appreciated that the technology in view of this field based on the disclosure stated herein, the compound covered herein and The specific dosage of composition can be by clinical trial and/or pharmacokinetic studies by empirically determined, and such dosage It can be adjusted according to prespecified validity and/or toxicity criterion.It will be further understood that the tool for any particular patient Body dosage and therapeutic scheme will depend on many factors, including the activity of used particular compound, the characteristic of patient, drug The property and severity of combination, the judgement for the treatment of physician and just treated specified disease or situation.
In embodiments, the composition stated, describe and/or covered herein can be used for treating-but it is not limited to-first fungi Disease, paronychia, excipuliform wart (verrucous wart), molluscum contagiosum (molluscum contagiosum), non-genitals list Pure bleb (non-genital herpes simplex), scar, Gram-negative toe web infect (gram negative toe- Web infection), nail psoriasis malnutritive (psoriatic nail dystrophy) and one kind in tinea pedis or It is more kinds of.In embodiments, composition includes PVP-I and DMSO.In embodiments, composition substantially by PVP-I and DMSO is formed.In embodiments, composition is made of PVP-I and DMSO.
In embodiments, by optimize one or more of compounds with the commonly used dosage form of the compound not With dosage form using preparing therapeutic combination.In embodiments, the compound that do not applied with topical formulations usually is developed For topical formulations.Chemical assay and bioassay needed for such exploitation are known to the skilled in the art.This paper's Disclosure provides to prepare such compound and the finger of the composition comprising such compound for technical staff It leads.
In embodiments, the method for subject of the treatment with otitis includes that application is stated, describes and/or covered herein Composition to treat otitis, and the treatment of otitis includes the progress for preventing or slowing down infection, the sprawling that prevents infection, is eliminated At least some and elimination all at least one of infection of infection.
In embodiments, therapeutic combination is administered with planning chart once a day.In embodiments, therapeutic combination Object application daily is twice.In embodiments, therapeutic combination application daily three times, four times per day, daily five times or more times. In embodiments, therapeutic combination less than frequency once a day to be administered.In embodiments, therapeutic combination is with every Once two days, once every three days, once every four days, once every five days, once every six days or every seven days are once administered.In reality It applies in scheme, therapeutic combination less than frequency once a week to be administered.In embodiments, therapeutic combination is monthly applied Once.In embodiments, therapeutic combination is monthly applied twice.
In embodiments, therapeutic administratp scheme for duration at least one day, at least two days, at least three days, at least four days, at least Five days, at least six days or at least seven days.In embodiments, therapeutic administratp scheme for duration at least one week, at least two weeks, at least three Week, at least surrounding, at least six weeks, at least eight weeks, at least ten weeks, at least 12 weeks, at least ten surroundings or at least 16 weeks.In reality It applies in scheme, therapeutic administratp scheme for duration at least one moon, at least two months, at least three months, at least four months, at least five The moon, at least six months, at least nine months or at least 12 months.
The present invention is further described by following embodiment.In one aspect, following embodiment demonstrates use by this public affairs Open the effective and/or successful treatment of composition and method that content covers to identified situation.It should be appreciated that being based on The variation of the feature of the present invention is in the technical scope of those of ordinary skill, and the scope of the present invention should not be limited by embodiment System.In order to suitably determine that the scope of the present invention, interested party are contemplated that the claims herein and its any equivalent. In addition, all quotations of this paper are incorporated by reference into, and unless explicitly stated, otherwise all percentages press weight Gauge.
Embodiment 1
With the acute otitis externa in the children of 2% povidone-iodine gel for treating
This patient just suffers from acute otitis externa.The situation is often very painful, when children's moving-head or movement Serious stimulation occurs.Use the 2.0%PVP-I and 2% hydroxyethyl cellulose (HEC) system in 44%USP grades of DMSO and water Standby composition as disclosed herein is to form thick gel.It is treated by the way that gel is locally applied to external auditory canal twice daily The patient.In four days, infection solves and the patient is not at pain.
Embodiment 2
With the acute otitis externa in the children of highly viscous 2% povidone-iodine gel for treating
This patient just suffers from acute otitis externa.The situation is often very painful, when children's moving-head or movement Serious stimulation occurs.Use the 2.0%PVP-I and 4% hydroxyethyl cellulose (HEC) system in 44%USP grades of DMSO and water Standby composition as disclosed herein is to form the sticky gel with the viscosity for being more than 300,000cps.By the way that gel is daily Once external auditory canal is locally applied to treat the patient.In two days, infection solves and the patient is not at pain.
It will be understood by those skilled in the art that variation can be made to the exemplary implementation scheme being shown and described above, and Without departing from its wide in range concept of the invention.It will be understood, therefore, that disclosure is not limited to shown and described exemplary reality Scheme is applied, but is intended to cover such as the modification in the spirit and scope of the present invention that are defined by the claims.For example, exemplary reality The specific features for applying scheme can be or can not be a part for claimed invention, and disclosed embodiment Feature can be combined.Unless specifically state herein, otherwise term " one (a) ", " one (an) " and " should (the) " be no It is limited to a kind of element, and should be understood that and mean "at least one".
It should be understood that at least some of in description of the invention be simplified to focus on it is related with the present invention is clearly understood that Element, while for purposes of clarity, eliminate those skilled in the art will appreciate that other element can also constitute this A part for invention.However, because such element is well known in the art, and because they not necessarily contribute to more preferably Ground understands the present invention, so not providing the description of such element herein.
In addition, in degree of this method independent of the specific sequence of steps stated herein, specific sequence of steps It is not construed as limitations on claims.
The claim for being related to the method for the present invention is not limited to the performance of its step in write sequence, and And skilled person can easily appreciate that these steps can change and still remain in the spirit and model of the present invention In enclosing.

Claims (14)

1. a kind of ear composition, including the DMSO of povidone-iodine of 0.1%w/w-10%w/w and 30%w/w-99%w/w with And acceptable excipient at least one otology.
2. composition as described in claim 1, wherein the composition includes gelling agent.
3. composition as claimed in claim 2, wherein the gelling agent be selected from hydroxyethyl cellulose, hydroxymethyl cellulose and Hydroxypropyl methyl cellulose.
4. composition as described in claim 1, wherein the composition includes PEG.
5. composition as described in claim 1, wherein the composition includes vaseline.
6. composition as described in claim 1, wherein the composition is no steroids.
7. a kind of method for preventing or treating ear infection or infect, the method includes：
The composition of application or application claim 1.
8. method as claimed in claim 6, wherein the ear infection or to infect be otitis externa.
9. method as claimed in claim 6, wherein the ear infection is tympanitis.
10. method as claimed in claim 6, wherein the ear infection is viral infection.
11. method as claimed in claim 6, wherein the ear infection or to infect be bacterium infection.
12. method as claimed in claim 6, wherein the ear infection or to infect be fungal infection.
13. method as claimed in claim 6, wherein the ear infection or infecting and being amoeba infection or infect.
14. the method for claim 7, wherein composition described in claim 1 is no steroids.
CN201780002919.6A 2016-11-02 2017-11-01 Compositions and methods for treating otitis Pending CN108472313A (en)

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Families Citing this family (3)

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JP2021161105A (en) * 2020-03-31 2021-10-11 タイ ミン ファーマシューティカルズ ジェイエスシー Composition for preventing or treating chronic or acute virus infection and/or sepsis in humans or animals
TW202203946A (en) * 2020-03-31 2022-02-01 越南商泰明製藥股份有限公司 Composition for preventing or treating chronic or acute virus infection and/or sepsis in humans or animals
FR3122572A1 (en) * 2021-05-07 2022-11-11 Nadine GRISLAIN Bioadhesive pharmaceutical composition comprising PVPI

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140205559A1 (en) * 2011-05-11 2014-07-24 Alc Therapeutics, Llc Antifungal compositions for the treatment of skin and nails

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4241051A (en) * 1977-11-04 1980-12-23 Christie Robert B Calcitonin
US8476319B2 (en) * 2005-03-10 2013-07-02 3M Innovative Properties Company Methods of treating ear infections
DE202005004183U1 (en) * 2005-03-14 2005-05-25 G. Pohl-Boskamp Gmbh & Co. Kg Formulation for analgesic ear drops contains polyhydric alcohol, especially butan-1,3-diol or glycerol, dimethyl sulfoxide and optionally acid or buffer system and dexpanthenol
US20060280809A1 (en) * 2005-06-14 2006-12-14 Leshchiner Adele K Anti-infective iodine based compositions for otic and nasal use
CN101002775A (en) * 2006-01-18 2007-07-25 广州白云山制药股份有限公司广州白云山制药总厂 Anti-inflective preparation
GB0709513D0 (en) * 2007-05-17 2007-06-27 Helperby Therapeutics Ltd Topical formulations
US20090263345A1 (en) * 2008-01-28 2009-10-22 Foresight Biotherapeutics, Inc. Otic compositions for the treatment of infections of the internal and external ear in mammals
US20100016450A1 (en) * 2008-07-21 2010-01-21 Otonomy, Inc. Controlled release delivery devices for the treatment of otic disorders
CN102811610B (en) * 2009-12-15 2016-05-18 前瞻生物治疗公司 Nonirritant ophthalmology PVP-I composition
HUE035586T2 (en) * 2010-01-07 2018-05-28 Univ Minnesota Methods and compositions for applying moxifloxacin to the ear
ES2391721T3 (en) * 2010-03-01 2012-11-29 Laboratorios Salvat, S.A. Transparent aqueous solutions of fluocinolone acetonide for the treatment of ear swelling
TW202126313A (en) * 2011-09-16 2021-07-16 美商遠景生物製藥股份有限公司 Stable povidone-iodine compositions
WO2014159930A1 (en) * 2013-03-14 2014-10-02 Alc Therapeutics, Llc Antifungal compositions for the treatment of secondary skin and nail infections
RU2666605C2 (en) * 2013-05-01 2018-09-11 Неокули Пти Лтд Methods of treating bacterial infections
AU2016209550A1 (en) * 2015-01-20 2017-08-03 Veloce Biopharma Llc Novel iodophor composition and methods of use

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140205559A1 (en) * 2011-05-11 2014-07-24 Alc Therapeutics, Llc Antifungal compositions for the treatment of skin and nails

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
吴红丽: "聚维酮碘治疗化脓性中耳炎合并真菌感染的临床特征及其预后影响因素分析", 《中国临床研究》 *
林洪斌: "聚维酮碘治疗外耳道真菌病65例", 《医药导报》 *

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