CN111249219B - Ear drops for treating fungus in auditory canal and preparation method thereof - Google Patents
Ear drops for treating fungus in auditory canal and preparation method thereof Download PDFInfo
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- CN111249219B CN111249219B CN201811460087.5A CN201811460087A CN111249219B CN 111249219 B CN111249219 B CN 111249219B CN 201811460087 A CN201811460087 A CN 201811460087A CN 111249219 B CN111249219 B CN 111249219B
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- ear canal
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Classifications
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- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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- A61P27/16—Otologicals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
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- General Chemical & Material Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an ear drop for treating ear canal fungi and a preparation method thereof, wherein the ear drop for treating ear canal fungi comprises the following components in percentage by mass: 3 to 20 percent of itraconazole, 2 to 10 percent of clotrimazole, 0.8 to 2.3 percent of carbomer-940, 5 to 15 percent of glycerol, 0.5 to 1.5 percent of triethanolamine and the balance of purified water. The preparation method comprises dissolving glycerol and carbomer-940 with purified water, adding triethanolamine during stirring, stirring to obtain transparent gel, adding itraconazole and clotrimazole into transparent gel, stirring, adding purified water to 100% of the total mass fraction, and stirring. The ear drop has the advantages of good antibacterial effect, high cure rate, convenient administration, uniform spraying, small stimulation to ears, easy preservation and the like, and the preparation method is simple and convenient and has low cost.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations and preparation thereof, relates to an ear drop for treating ear canal fungi and a preparation method thereof, and in particular relates to an ear drop for treating ear canal fungi by combining itraconazole with clotrimazole and a preparation method thereof.
Background
The ear canal mycosis is a kind of fungus infection caused by the growth and reproduction of fungus growing in the ear canal, and is mainly infected by saccharomycetes, candida, blastomycosis, aspergillus and other germs. Once the disease is started, ear itching can be accompanied by ear pain, and the itching of some patients with fungal auditory canal diseases can be more severe at night, if the patients are scratched repeatedly by hands at the moment, the skin of the external auditory canal is easy to be scratched to cause bleeding, secondary infection, running water and the like. Severe cases may even cause dizziness, facial paralysis, and necrotic otitis externa.
The pH value and humidity in the external auditory canal are changed by the fungal patients in the auditory canal due to the factors of pus stimulation, swimming, ear digging and the like, so that the fungal patients in the auditory canal are easy to cause the disease. In addition, patients with low collective resistance and long-term oral administration of antibiotics and hormones are also susceptible to this disease. And the prevalence rate is increasing, more and more patients with fungal infection of the auditory canal come to the hospital for treatment. The main pathogenic bacteria include yeast, candida, pullulans, aspergillus, mucor, actinomycetes, penicillium, etc. Oral drug therapy cannot effectively act on a target position, and local administration is reasonable and effective.
The clinic treatment for the otomycosis mainly comprises the following methods by taking an external medicine as a main part:
(1) After the ear is thoroughly debrided, fungus inhibiting solutions such as boric acid alcohol, salicylic acid alcohol and compound resorcinol solution are used for ear dripping, the method is simple to operate, but the medicaments can generate cauterization, stinging and other reactions after being used, so that the treatment compliance of patients is seriously influenced, the treatment thoroughness is difficult to ensure, and the medicinal liquid has the defects of difficult preparation, non-ideal preservation and the like.
(2) The conventional medicines such as clotrimazole ointment, dacron Ning Shuang and the like are used for coating, so that the medicine has the advantage of mild medicine property, does not generate adverse reaction, has poor overall curative effect, is difficult to accept by patients, and is difficult to uniformly coat the medicine on all parts suffering from diseases due to physiological bending and stenosis of external auditory meatus.
(3) The ear bath treatment with antifungal medicine, such as fluconazole injection, has long duration of the liquid medicine in the external auditory canal, and the liquid medicine soaking the whole external auditory canal has better treatment effect than the two methods, but has certain irritation and can not ensure stable clinical effect.
The antifungal medicines in the market are mostly in the form of azoles, and most of the antifungal medicines are orally taken, and the ear drop preparation is a good choice for treating the fungus in the auditory canal, and although the application of the ear drop preparation containing itraconazole or voriconazole and other components is not universal, the main reason is that the prescription of the preparation is not mature enough, and the safety and the effectiveness are yet to be researched and proved. Therefore, in order to solve the inconvenience and the defect of the treatment effect of the current treatment mode, development of a novel fungus preparation for auditory meatus is urgently needed.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the ear drops for treating the fungus in the auditory canal, which have the advantages of good antibacterial effect, high cure rate, simple administration, uniform spraying, small stimulation to the ear and easy preservation, and the preparation method thereof.
In order to solve the technical problems, the invention adopts the following technical scheme.
An ear drop for treating ear canal fungi, which comprises the following components in percentage by mass:
in the ear drops for treating the ear canal fungi, preferably, the ear drops for treating the ear canal fungi comprise the following components in percentage by mass:
in the ear drops for treating the ear canal fungi, preferably, the ear drops for treating the ear canal fungi further comprise one or more of a suspension stabilizer, a transdermal agent and a preservative, wherein the moisture retention solubilizer accounts for 0.6-1.2% of the weight of the ear drops, the transdermal agent accounts for 0.55-1.5% of the weight of the ear drops, and the preservative accounts for 0.03-0.1% of the weight of the ear drops.
In the above ear drops for treating fungus in ear canal, preferably, the preservative comprises one or more of lysozyme, methyl paraben, ethyl paraben and benzoic acid.
In the ear drops for treating the fungus in the auditory canal, preferably, the lysozyme is chitinase and/or dextranase.
In the ear drops for treating the fungus in the ear canal, preferably, the moisturizing solubilizer includes one or more of PEG-400, propylene glycol and ethanol.
In the ear drops for treating fungus in auditory canal, preferably, the transdermal agent includes one or more of borneol, laurocapram, menthol and azone.
As a general technical conception, the invention also provides a preparation method of the ear drops for treating the fungus in the auditory canal, which comprises the following steps: dissolving glycerol and carbomer-940 with purified water, adding triethanolamine during stirring, stirring to obtain transparent gel, adding itraconazole and clotrimazole into the transparent gel, stirring, adding purified water to 100% of the total mass fraction, and stirring to obtain ear drop for treating ear canal fungus.
As a general technical conception, the invention also provides a preparation method of the ear drops for treating the fungus in the auditory canal, which comprises the following steps: dissolving a moisturizing solubilizer, carbomer-940 and glycerol with purified water, adding triethanolamine in the stirring process, stirring to obtain transparent gel, adding itraconazole and clotrimazole into the transparent gel, stirring, adding a transdermal agent and a preservative, adding purified water until the total mass fraction is 100%, and stirring uniformly to obtain the ear drops for treating the ear canal fungi.
The invention aims to provide an ear drop for effectively controlling and treating ear canal mycosis and a preparation method thereof. There are few agents currently dedicated to the treatment of ear canal mycoses and there are no drugs for the treatment of ear canal mycoses in many hospitals, even in trimethyl hospitals. At present, no clear method is available for treating the ear canal mycosis in clinic, the selection of medicines is less, the treatment effect is not clear, and the more reasonable fluconazole injection is not originally used for treating the ear canal mycosis, so the invention provides an effective and applicable ear drop multi-dosage form, and can provide the selection for doctors and patients to treat the ear canal mycosis. The main pathogenic fungi for the infection of the ear canal fungi are saccharomycetes, candida, blastomyces, aspergillus, mucor, actinomycetes, penicillium and the like, and single antifungal drugs can not achieve the optimal treatment effect sometimes, so the invention creatively selects itraconazole and clotrimazole as main components of a compound preparation to better synergistically treat the ear canal fungi through experimental study, wherein a moisturizing solubilizer (such as PEG-400, namely polyethylene glycol 400) promotes the dissolution of the drugs, glycerol is a viscous agent, promotes the transdermal absorption of the drugs, triethanolamine is an emulsifying agent and a pH regulator, purified water is a solvent, and promotes the dissolution, the mixing and the synergistic effect of the components.
Particularly, the invention provides that lysozyme can be used as a natural medicine preservative material in ear drops for the first time, and replaces the conventional preservative, and the lysozyme can adopt chitinase and/or glucanase.
Compared with the prior art, the invention has the advantages that:
1. the invention uses broad-spectrum antifungal medicines, namely Itraconazole and clotrimazole, as main medicinal components to prepare clinical preparations, and Itraconazole (Itraconazole) is an artificially synthesized triazole derivative, is a synthetic broad-spectrum antifungal medicine, exerts antibacterial activity by changing the permeability of fungal cell membranes, has antibacterial activity on pathogenic bacteria of shallow and deep fungal infections, and has wide antibacterial spectrum. Clotrimazole is an imidazole derivative, is a broad-spectrum antifungal agent, can destroy fungal cell membranes to enable cell contents to leak out and kill fungi, is low in cost, is widely used in fungal dermatological infection, and is mainly used for local application. The ear drop provided by the invention can effectively inhibit the propagation and growth of various ear canal fungi.
In the prior art, ethanol is mostly selected as a solvent to improve the permeability and sterilization effect of the medicine, but the ethanol has strong irritation, particularly the skin in the ear is sensitive, the discomfort of a patient is more easily caused, and the compliance of the patient is seriously influenced. In order to enhance the absorption of the medicine, the azone with strong transdermal absorption and less skin irritation can be preferably used as a transdermal absorbent to cooperatively enhance the rapid entry of the medicine into the body. The ear drop preparation is a single medicinal preparation at present, but the invention is a composite preparation of two azole medicaments, the solubility of the hydrophobic medicament in a solvent is increased by adding a moisturizing solubilizer and glycerol, triethanolamine is used as a safe and efficient emulsifier to promote the formation of gel, finally purified water is added to fully and uniformly mix and dissolve the medicament to form a relatively stable medicinal preparation (the viscosity can be slightly higher than that of pure liquid), and finally the service life of the medicament is prolonged by adding a natural harmless preservative to ensure the curative effect of the medicament to be stable. Particularly, the lysozyme (commercially available) selected by the invention is prepared by cloning and extracting by adopting a bioengineering technology, is a natural enzyme, is a safe and green additive, and has no drug resistance. The auxiliary materials of the product can use lysozyme to replace a chemical preservative which is conventionally used, so that the quality guarantee period of the medicine can be prolonged, the medicine is harmless to human bodies, and besides, the lysozyme has an inhibiting effect on fungi, and the lysozyme and the medicine have the synergistic effect of inhibiting the propagation and growth of the fungi, which has not been proposed in the prior art.
2. The ear drops for treating the fungus in the auditory canal has the advantages of no irritation, obvious treatment effect, lower cost, convenient use, low price, simple preparation and controllable quality, and greatly increases the cure rate of the fungus infection in the external auditory canal.
3. The preparation method is simple and convenient and has low cost.
Detailed Description
The invention is further described below in connection with specific preferred embodiments, but it is not intended to limit the scope of the invention.
The materials and instruments used in the examples below are all commercially available.
Example 1:
the ear drops for treating the fungus in the auditory canal comprise the following components in percentage by mass:
the preparation method of the ear drops for treating the fungus in the auditory canal of the embodiment comprises the following steps:
mixing carbomer-940, PEG-400, glycerol and purified water with appropriate amount of the three substances dissolved, stirring, adding triethanolamine, and stirring to obtain transparent gel. Adding itraconazole and clotrimazole into gel, stirring, adding azone, chitinase and glucanase, adding purified water to 100g, and stirring to obtain ear drops for treating ear canal fungi.
The ear drops prepared in this embodiment can be loaded by using an existing bottled container suitable for ear drops, preferably, the bottled container has a plastic hose capable of extending into an ear canal, and the dropper head adopts silica gel, so that the damage to the ear tissues is avoided. The medicine is sprayed into the external auditory canal through the bottled container and is used for the administration treatment of the external auditory canal.
Example 2:
the ear drops for treating the fungus in the auditory canal comprise the following components in percentage by mass:
the preparation method of this example is the same as that of example 1.
Example 3:
the ear drops for treating the fungus in the auditory canal comprise the following components in percentage by mass:
the preparation method of this example is the same as that of example 1.
Example 4:
to compare the therapeutic effects of the natural preservative with that of the chemical preservative, the chitinase and glucanase of example 3 were exchanged for methyl paraben.
The ear drops for treating the fungus in the auditory canal comprise the following components in percentage by mass:
the preparation method of this example is the same as that of example 1.
In vitro test:
pharmacological and toxicology experimental researches on the anti-ear canal fungus spray provided by the invention.
(1) In vitro bacteriostasis experiment: the in vitro bacteriostasis test uses oxford cup method and compares with sterile pure water (blank control). The specific operation steps are as follows: activating preserved mould, yeast and candida respectively to prepare bacterial suspension, and regulating the concentration of the bacterial suspension to 10 6 CFU/mL, preparing a bacteriostatic flat plate by adopting a coating method, coating uniformly, and ensuring that the bacterial liquid cannot excessively flow on the flat plate, wherein the bacteriostatic effect of the preparation of each embodiment is compared by adopting an oxford cup bacteriostatic ring method after the preparation is prepared. Firstly, after the sterilizing oxford cup is quickly overfired on the flame of the alcohol lamp, the sterilizing oxford cup is vertically placed on the surface of a bacteria-inhibiting flat-plate culture medium, and is lightly pressed to form a gap between the cup bottom and the culture medium. 5 oxford cups (including 4 example prescriptions and sterile pure water controls) were placed on each plate, and 200 microliters of the drug solution or sterile pure water was injected into each oxford cup. 3 replicates of each bacteriostatic plate were incubated at 37℃for 24h, observed, measured and recorded. And referring to the in-vitro drug sensitivity judging standard of the antibacterial drugs of American clinical and laboratory standards institute, wherein the diameter of the inhibition ring is more than 20mm and is highly sensitive, the diameter of the inhibition ring is 10-20 mm and is moderately sensitive, and the diameter of the inhibition ring is less than 10mm and is drug resistant or ineffective. Thus, as can be seen from Table 1, the present inventionThe prescription preparation of 4 examples has strong anti-aspergillus, saccharomycete and candida effects, and the drug sensitivity is high.
Table 1 each example and in vitro bacteriostasis test of sterile pure water mean unit: millimeter (mm)
Note that: each set of experiments was repeated 3 times.
(2) Toxicology experiments: acute toxicity test the experimental mice were randomized into two groups, namely high dose and low dose groups, which were intragastric. The low dose group is irrigated with stomach 10 times of the percutaneous absorption of the medicine, and the high dose group is irrigated with stomach 500 times of the percutaneous absorption of the medicine. As a result, mice die after stomach irrigation, which indicates that the medicine is nontoxic and is safe to use as ear drops. The test results are shown in Table 2 below.
Table 2 acute toxicity test of examples
(3) Skin irritation test: the white rabbits were dehaired on both sides of the back 24 hours before dosing, but without damaging the skin. In the experiment, 2ml of ear drop and 2ml of physiological saline are respectively dropped on disinfection filter paper and stuck on the left side and the right side back of a rabbit, one layer of oilpaper and two layers of gauze are covered, the rabbit is sealed by rubberized fabric, and the skin irritation response of the rabbit by the medicine is checked at 30 minutes, 60 minutes, 24 hours and 48 hours respectively. As a result, the skin of the rabbit has no erythema or edema, which indicates that the medicine has no irritation to the skin. The test results are shown in Table 3.
Note that: "-" indicates symptom-negative, without erythema and edema.
Example 3 and example 4 were prepared in the same manner, with the only difference that the preservative was selected differently, and it was observed through in vitro experiments that the bacteriostatic effect of example 4 and the skin irritation test were not as good as example 3, and the toxicology test was consistent. We can derive: the antibacterial effect of the natural preservative lysozyme is stronger than that of the common chemical preservative, and the product is safe and effective.
The above description is only of the preferred embodiment of the present invention, and is not intended to limit the present invention in any way. While the invention has been described in terms of preferred embodiments, it is not intended to be limiting. Any person skilled in the art can make many possible variations and modifications to the technical solution of the present invention or equivalent embodiments using the method and technical solution disclosed above without departing from the spirit and technical solution of the present invention. Therefore, any simple modification, equivalent substitution, equivalent variation and modification of the above embodiments according to the technical substance of the present invention, which do not depart from the technical solution of the present invention, still fall within the scope of the technical solution of the present invention.
Claims (5)
1. The ear drop for treating the ear canal fungi is characterized by comprising the following components in percentage by mass:
the ear drop for treating the ear canal fungi also comprises a moisturizing solubilizer, a transdermal agent and a preservative, wherein the moisturizing solubilizer is 0.6-1.2% by mass, the transdermal agent is 0.55-1.5% by mass, and the preservative is 0.03-0.1% by mass;
the preservative is lysozyme, and the lysozyme is chitinase and glucanase.
2. The ear drops for treating ear canal fungi according to claim 1, characterized in that the ear drops for treating ear canal fungi consist of the following components in mass fraction:
the ear drop for treating the ear canal fungi also comprises a moisturizing solubilizer, a transdermal agent and a preservative, wherein the moisturizing solubilizer is 0.6-1.2% by mass, the transdermal agent is 0.55-1.5% by mass, and the preservative is 0.03-0.1% by mass;
the preservative is lysozyme, and the lysozyme is chitinase and glucanase.
3. The ear drops for the treatment of ear canal fungi according to claim 1 or 2, wherein the moisturizing solubilizer comprises one or more of PEG-400, propylene glycol and ethanol.
4. The ear drops for treating ear canal fungi of claim 1 or 2, wherein the transdermal agent comprises one or more of borneol, laurocapram, menthol and azone.
5. A method of preparing an ear drop for the treatment of ear canal fungi according to any of claims 1-4, comprising the steps of: dissolving a moisturizing solubilizer, carbomer-940 and glycerol with purified water, adding triethanolamine in the stirring process, stirring to obtain transparent gel, adding itraconazole and clotrimazole into the transparent gel, stirring, adding a transdermal agent and a preservative, adding purified water until the total mass fraction is 100%, and stirring uniformly to obtain the ear drops for treating the ear canal fungi.
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999020261A2 (en) * | 1997-10-22 | 1999-04-29 | Jens Ponikau | Use of antigunal agents for the topial treatment of fungus-induced mucositis |
CN1372974A (en) * | 2001-03-02 | 2002-10-09 | 凌沛学 | Exterior-applied gel contaiing lysozyme as primary component and its preparing process |
CN1380060A (en) * | 2002-04-28 | 2002-11-20 | 中国人民解放军第二军医大学 | Solution type spray of antimycotic medicine for external application and its preparation method |
RU2004111595A (en) * | 2001-10-16 | 2005-04-10 | МакНЕЙЛ-ППС, ИНК. (US) | NEW METHODS FOR TREATING LOCAL FUNGAL AND BACTERIAL INFECTIONS |
CN102505180A (en) * | 2011-09-16 | 2012-06-20 | 彭可扬 | Itraconazole-lysozyme loaded electro-spun fibrous membrane for preventing and controlling indoor microbial pollution |
CN102526132A (en) * | 2012-02-13 | 2012-07-04 | 曹汉海 | Antifungal ear drops and preparation method thereof |
CN103182074A (en) * | 2011-12-30 | 2013-07-03 | 沈阳兴齐眼药股份有限公司 | Ophthalmic preparation containing lysozyme |
CN107854427A (en) * | 2017-11-09 | 2018-03-30 | 广州博济医药生物技术股份有限公司 | A kind of Fluconazole auristilla and preparation method thereof |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050043251A1 (en) * | 2003-08-20 | 2005-02-24 | Fairfield Clinical Trials, Llc | Method of treatment of otitis externa |
US20070054844A1 (en) * | 2003-08-20 | 2007-03-08 | Fairfield Clinical Trials, Llc | Method for treating otitis externa |
-
2018
- 2018-11-30 CN CN201811460087.5A patent/CN111249219B/en active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999020261A2 (en) * | 1997-10-22 | 1999-04-29 | Jens Ponikau | Use of antigunal agents for the topial treatment of fungus-induced mucositis |
CN1372974A (en) * | 2001-03-02 | 2002-10-09 | 凌沛学 | Exterior-applied gel contaiing lysozyme as primary component and its preparing process |
RU2004111595A (en) * | 2001-10-16 | 2005-04-10 | МакНЕЙЛ-ППС, ИНК. (US) | NEW METHODS FOR TREATING LOCAL FUNGAL AND BACTERIAL INFECTIONS |
CN1380060A (en) * | 2002-04-28 | 2002-11-20 | 中国人民解放军第二军医大学 | Solution type spray of antimycotic medicine for external application and its preparation method |
CN102505180A (en) * | 2011-09-16 | 2012-06-20 | 彭可扬 | Itraconazole-lysozyme loaded electro-spun fibrous membrane for preventing and controlling indoor microbial pollution |
CN103182074A (en) * | 2011-12-30 | 2013-07-03 | 沈阳兴齐眼药股份有限公司 | Ophthalmic preparation containing lysozyme |
CN102526132A (en) * | 2012-02-13 | 2012-07-04 | 曹汉海 | Antifungal ear drops and preparation method thereof |
CN107854427A (en) * | 2017-11-09 | 2018-03-30 | 广州博济医药生物技术股份有限公司 | A kind of Fluconazole auristilla and preparation method thereof |
Non-Patent Citations (1)
Title |
---|
空腹或餐后服用国产伊曲康唑胶囊的人体生物等效性研究;黄洁;临床药理学;第18卷;527-531 * |
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