CN114886839A - Naftifine ketoconazole gel composition and preparation method thereof - Google Patents

Naftifine ketoconazole gel composition and preparation method thereof Download PDF

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CN114886839A
CN114886839A CN202210506360.3A CN202210506360A CN114886839A CN 114886839 A CN114886839 A CN 114886839A CN 202210506360 A CN202210506360 A CN 202210506360A CN 114886839 A CN114886839 A CN 114886839A
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ketoconazole
naftifine
gel
gel composition
prescription amount
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CN114886839B (en
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姜春阳
谢军
李惠
华丽
黄利明
刘丽芳
牛娅
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Shanghai Scienpharm Biotechnology Co ltd
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    • 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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • 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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Abstract

The invention discloses a naftifine and ketoconazole gel composition and a preparation method thereof. The gel is an aqueous gel matrix and consists of naftifine hydrochloride, ketoconazole, a thickening agent, an emulsifying agent, a solubilizing agent, a solvent, an emollient, an antioxidant, a chelating agent and a proper amount of pH regulator. The proportions of the naftifine hydrochloride and the ketoconazole in the gel are respectively 0.7-0.9% and 0.1-0.2%, which are far lower than the naftifine ketoconazole cream sold in the market, and the skin retention is similar to the naftifine ketoconazole cream. The preparation has stable property, is easy to apply, is not suitable to remain on the surface of skin, has good skin moistening effect, and is more acceptable to patients.

Description

Naftifine ketoconazole gel composition and preparation method thereof
Technical Field
The invention belongs to the field of pharmaceutical preparations, relates to a gel composition and a preparation method thereof, and particularly relates to a naftifine ketoconazole gel composition which is good in stability, has a low content of active substances and has an ideal skin retention amount.
Background
Ketoconazole is an azole antifungal drug, and inhibits the biosynthesis of ergosterol, an important component of fungal cell membranes. Ketoconazole drugs deplete ergosterol from fungal cell membranes, disrupting the structure and various functions of the fungal cell membrane, thereby inhibiting fungal growth. The target molecule of action is lanosterol-14-alpha-demethylase, as with other imidazole antifungal drugs.
Naftifine hydrochloride is an antifungal drug based on allylamine, can inhibit the synthesis of ergosterol which is a main component of fungal cell membranes, and damages the functions of the fungal cell membranes, but has an action mechanism of inhibiting squalene epoxidase.
Naftifine hydrochloride and ketoconazole which are used as active medicaments for treating fungal skin diseases, the medicaments which are currently marketed in China include naftifine hydrochloride cream, ointment and solution, ketoconazole cream and naftifine ketoconazole cream, and no gel is marketed. The naftifine ketoconazole cream is a compound preparation consisting of 1 percent of naftifine hydrochloride and 0.25 percent of ketoconazole, is the first new drug to be marketed in China by Chongqing Huabang in 10 months in 2005, and is characterized in that the naftifine and the ketoconazole hydrochloride are mixed according to the proportion of 1: 4, the concentration of active ingredients is 1 percent of naftifine hydrochloride and 0.25 percent of ketoconazole, which is far lower than the concentration of the ketoconazole in the single ketoconazole cream by 2 percent, thereby reducing toxic and side effects and playing a role in synergistic antibacterial action after being used together.
The gel composition containing naftifine and ketoconazole has higher skin retention, can obviously reduce the concentration of active substances in a preparation formula, and can achieve the same curative effect as a commercial naftifine ketoconazole cream (trade name: Bi Liang).
Disclosure of Invention
The invention aims to develop an allylamine drug and an azole drug which are combined for use, provide synergistic effect through different action mechanisms, have the antibacterial effect similar to that of a commercial naftifine ketoconazole cream (the trade name is Bi-bright), and have the proportions of naftifine hydrochloride and ketoconazole in gel of 0.7-0.9 percent and 0.1-0.2 percent which are far lower than that of the commercial naftifine ketoconazole cream (naftifine hydrochloride is 1 percent and ketoconazole is 0.25 percent)
The invention aims to overcome the defects in the prior art and provide a gel composition containing naftifine ketoconazole.
The purpose of the invention is realized by the following technical scheme:
the invention relates to a gel composition containing naftifine and ketoconazole, wherein the gel is an aqueous gel matrix. The naftifine hydrochloride and ketoconazole active ingredients and the auxiliary materials of the external preparation comprise a thickening agent, an emulsifying agent, a solubilizing agent, a solvent, an emollient, an antioxidant, a chelating agent and a pH regulator.
As an embodiment, the active ingredients and the auxiliary materials are respectively in the following weight percentage based on the total weight of the naftifine ketoconazole gel composition: 0.7-0.9% of naftifine hydrochloride, 0.1-0.2% of ketoconazole, 3-6% of thickening agent, 0.1-1% of emulsifying agent, 2-6% of solubilizer, 3-5% of solvent, 4-6% of emollient, 0.1-0.2% of antioxidant, 0.05-0.1% of chelating agent, and a proper amount of pH regulator and water.
As an embodiment, the weight ratio of naftifine hydrochloride to ketoconazole is preferably 6.4: 1.
as an embodiment, the aqueous gel matrix comprises 0.8% of naftifine hydrochloride and 0.125% of ketoconazole, based on the total weight of the naftifine ketoconazole gel in percentage by mass.
As an embodiment, the thickener selected is selected from the group consisting of acrylamide/sodium acryloyldimethyl taurate copolymer Simulgel 600PHA in a proportion of 3 to 6% by mass, preferably 3.5 to 4.5% by mass, based on the total weight of the naftifine ketoconazole gel.
As an embodiment, the emulsifier is selected from one or more of polyoxyethylene ether, tween 60 and docusate sodium, and the proportion of the emulsifier is 0.1-1%, preferably 0.2-0.8% in mass percentage based on the total weight of the naftifine ketoconazole gel.
As an embodiment, the solubilizer is selected from one or two of diethylene glycol monoethyl ether and caprylic capric polyethylene glycol glyceride, and accounts for 2-6% of the total weight of the naftifine ketoconazole gel in percentage by mass, and preferably 3-5%.
As an embodiment, the solvent is selected from one or two of benzyl alcohol and propylene glycol, and the content of the solvent is in the range of 3-5% in mass percentage based on the total weight of the naftifine ketoconazole gel.
As an embodiment, the emollient is selected from any one or more of propylene glycol dipelargonate, polydimethylsiloxane 350, polyethylene glycol-7 cocoglyceride, preferably one or two of propylene glycol dipelargonate and polydimethylsiloxane 350, and accounts for 4-6% of the total mass of the naftifine ketoconazole gel.
As an embodiment, the antioxidant is selected from sodium sulfite, sodium metabisulfite and butyl hydroxy toluene, and is 0.1-0.2% of the total weight of the naftifine ketoconazole gel in percentage by mass.
As an embodiment, the chelating agent is selected from disodium edetate and sodium calcium edetate, and the content of the chelating agent is 0.05-0.1% by mass of the total weight of the naftifine ketoconazole gel.
The pharmaceutical composition gel pH regulator comprises adjuvants such as hydrochloric acid, sodium hydroxide, potassium hydroxide, etc. common chelating agent for topical gel medicine. Preferably, the pH adjusting agent is sodium hydroxide.
As an embodiment, the naftifine ketoconazole gel provided by the invention comprises the following raw materials, auxiliary materials and formula (in percentage by mass based on the total weight of the naftifine ketoconazole gel): naftifine hydrochloride 0.8%, ketoconazole 0.125%, thickening agent 3-6%, emulsifying agent 0.1-1%, solubilizing agent 2-6%, solvent 3-5%, emollient 4-6%, antioxidant 0.1-0.2%, chelating agent 0.05-0.1%, water 74.60-86.95% and a proper amount of pH regulator.
As an embodiment, the naftifine ketoconazole gel provided by the invention comprises the following raw materials, auxiliary materials and formula (in percentage by mass based on the total weight of the naftifine ketoconazole gel): 0.7-0.9% of naftifine hydrochloride, 0.1-0.2% of ketoconazole, 4% of thickening agent, 0.2% of emulsifying agent, 3.5% of solubilizer, 4% of solvent, 5% of emollient, 0.1-0.2% of antioxidant, 0.05-0.1% of chelating agent, 74.60-86.95% of water and a proper amount of pH regulator.
As an embodiment, naftifine hydrochloride is slightly soluble in water, ketoconazole is hardly soluble in water, ketoconazole is unstable under acidic conditions, naftifine hydrochloride is acidic, the two active substances are directly mixed to cause degradation of ketoconazole and change of properties, so that the gel cannot be prepared into a non-aqueous gel, the compound needs to be prepared into a water gel according to the compatibility problem of the two active ingredients, naftifine hydrochloride dispersion liquid is preferentially added into an aqueous matrix, and the gel dispersion liquid is added after the pH value is adjusted to 6.5-7.5.
The invention also relates to a preparation method of the naftifine ketoconazole gel, which comprises the following steps:
(1) preparing an active phase I: taking naftifine hydrochloride with the prescription amount, solubilizer with the prescription amount of 50 percent and solvent with the prescription amount of 50 percent, heating to 60-70 ℃ for dissolving for later use.
(2) Preparing an active phase II: taking ketoconazole with the prescription amount, solubilizer with the prescription amount of 50 percent and solvent with the prescription amount of 50 percent, heating to 40-50 ℃ for dissolving for later use.
(3) Preparation of gel matrix: taking the thickening agent according to the prescription amount, adding the water and the emulsifier according to the prescription amount at the temperature of 30-40 ℃, stirring and dispersing, adding the emollient chelating agent and the antioxidant according to the prescription amount after uniform dispersion, and stirring uniformly.
(4) Adding the active phase I into the mixture obtained in the step (3), uniformly stirring, and adjusting the pH value to 6.5-7.5 by using sodium hydroxide. And (3) after uniformly stirring, adding the active phase II, and uniformly stirring to obtain the naftifine ketoconazole gel.
As an embodiment, naftifine hydrochloride and ketoconazole are dispersed in 50% of the prescribed amount of solvent and solubilizer, respectively, and dissolved with stirring.
The invention also relates to the application of the naftifine ketoconazole gel composition in preparing a medicament for treating fungal skin diseases, such as tinea manus and pedis, tinea corporis and cruris, tinea capitis, cutaneous candidiasis and the like.
Compared with the prior art, the invention has the following beneficial effects:
the invention provides a naftifine ketoconazole gel composition and a preparation method thereof, wherein the proportions of naftifine hydrochloride and ketoconazole in the gel are 0.7% -0.9% and 0.1% -0.2%, which are far lower than those of naftifine ketoconazole cream sold in the market (naftifine hydrochloride is 1% and ketoconazole is 0.25%), and the naftifine ketoconazole gel composition has similar skin retention amount with the naftifine ketoconazole cream sold in the market. The preparation has stable property, is easy to apply, is not suitable to remain on the surface of skin, has good skin moistening effect, and is more acceptable to patients.
Drawings
Other features, objects and advantages of the invention will become more apparent upon reading of the detailed description of non-limiting embodiments with reference to the following drawings:
fig. 1 is a picture of the appearance of the gel of example 1.
Detailed Description
The present invention will be described in detail with reference to examples. The following examples will assist those skilled in the art in further understanding the invention, but are not intended to limit the invention in any way. It should be noted that numerous modifications and adaptations can be made by those skilled in the art without departing from the inventive concepts herein. All falling within the scope of the present invention.
The naftifine ketoconazole gel is an aqueous gel, and comprises naftifine hydrochloride, ketoconazole active ingredients and auxiliary materials of an external preparation, wherein the auxiliary materials comprise a thickening agent, an emulsifying agent, a solubilizer, a solvent, an emollient, an antioxidant, a chelating agent and a pH regulator. The active ingredients and the auxiliary materials in the total weight of the gel composition are respectively as follows by mass percent: 0.7-0.9% of naftifine hydrochloride, 0.1-0.2% of ketoconazole, 3-6% of thickening agent, 0.1-1% of emulsifying agent, 2-6% of solubilizer, 3-5% of solvent, 4-6% of emollient, 0.1-0.2% of antioxidant, 0.05-0.1% of chelating agent, a proper amount of pH regulator and the balance of water, wherein the balance of the water is determined by weight to 100.
The preparation method of the naftifine ketoconazole gel comprises the following steps:
(1) preparing an active phase I: taking naftifine hydrochloride with the prescription amount, solubilizer with the prescription amount of 50 percent and solvent with the prescription amount of 50 percent, heating to 60-70 ℃ for dissolving for later use.
(2) Preparing an active phase II: taking ketoconazole with the prescription amount, solubilizer with the prescription amount of 50 percent and solvent with the prescription amount of 50 percent, heating to 40-50 ℃ for dissolving for later use.
(3) Preparation of gel matrix: taking acrylamide/sodium acryloyldimethyl taurate copolymer according to the prescription amount at the temperature of 30-40 ℃, adding water and an emulsifier according to the prescription amount, stirring and dispersing, adding an emollient, a chelating agent and an antioxidant according to the prescription amount after uniform dispersion, and stirring uniformly.
(4) Adding the active phase I into the mixture obtained in the step (3), uniformly stirring, and adjusting the pH value to 6.5-7.5 by using sodium hydroxide. And (3) after uniformly stirring, adding the active phase II, and uniformly stirring to obtain the naftifine ketoconazole gel.
Specific application examples are as follows:
examples 1 to 4
The matrix is acrylamide gel, and the gel matrix comprises a thickening agent, an emulsifier, a solubilizer, a solvent, an emollient, a chelating agent, an antioxidant, a pH regulator and the like, and is shown in table 1.
TABLE 1
Figure BDA0003636322380000041
Figure BDA0003636322380000051
The acrylamide auxiliary material is used as a thickening agent of the gel matrix, the gel matrix contains an emulsifier, a solubilizer, a solvent, an emollient, a chelating agent, an antioxidant and the like, and the prepared gel is not layered, and related substances and contents meet the requirements of preparations.
Comparative example 1:
the preparation was carried out as described in examples 1 to 4, and the recipe is given in Table 2.
TABLE 2
Figure BDA0003636322380000052
Example 5
The viscosity, centrifugation, properties, pH, content, related substances and content uniformity, etc. of the naftifine ketoconazole creams (trade name: Biliang) of examples 1 to 4 and comparative example 1 and the commercial naftifine ketoconazole cream were measured, and the results are shown in Table 3 below.
TABLE 3
Figure BDA0003636322380000061
The comparison result of the quality indexes shows that the naftifine ketoconazole gel prepared by the patent formula and the preparation process is centrifuged at 10000rpm for 15 minutes at room temperature, the naftifine ketoconazole gel is not layered, the naftifine ketoconazole cream is layered, and other indexes of the gel are similar to those of the cream.
Example 6
The long-term stability of the cream of examples 1 to 4, comparative example 1 and naftifine ketoconazole (trade name: Biliang) was examined, and the cream was placed at 30 + -2 deg.C and RH 60% + -5% and sampled for detection of properties, viscosity, pH, content and related substances at 3 months and 6 months, respectively, and the specific detection results are shown in tables 4 and 5 below.
TABLE 4
Figure BDA0003636322380000062
Figure BDA0003636322380000071
TABLE 5
Figure BDA0003636322380000072
The stability comparison result shows that the viscosity of the naftifine ketoconazole gel prepared by the prescription and the preparation process is kept stable within 6 months for a long time, the impurities are not obviously increased basically, the naftifine ketoconazole cream (bright) has certain viscosity reduction, and related substances are slightly increased. The naftifine ketoconazole gel prepared according to the patent formula and the preparation process has good stability.
Example 7 comparison of in vitro transdermal test data
In vitro transdermal test
The method comprises the following steps: franz diffusion cell process
The instrument comprises the following steps: SYSTEM 918-12 DRY HEATING AUTOMATIC PERMEABILITY SYSTEM, PRODUCT LOgan Instruments Corp (LU LONG INSTRUMENT, Inc.)
Skin: the experimental pigskin has the thickness of 0.8-1mm and the contact diameter of 15mm
Receiving liquid: physiological saline
Temperature of the receiving solution: 32 + -0.5 deg.C
Rotating speed: 600rpm
Sample preparation: accurately weighing about 300mg of gel or cream sample of each prescription respectively, uniformly coating on experimental pigskin, repeatedly coating 3 samples per prescription, and taking pigskin without cream as blank pigskin.
Volume of the diffusion cell: 12ml of
Test time: 24 hours
Determination of drug retention
After the transdermal experiment is finished, taking down the pigskin, removing residual drug preparations, washing the pigskin with normal saline, sucking dry by using filter paper, taking about 0.1g of the filter paper, precisely weighing the filter paper, adding 2.0ml of water, homogenizing, taking 1ml of the filtered pigskin, filtering the filtrate into a liquid phase to measure naftifine and ketoconazole in the pigskin, and calculating the skin retention of each preparation, wherein the results are shown in table 6. In the table, KCZ represents ketoconazole, and NTF represents naftifine.
TABLE 6
Figure BDA0003636322380000081
As can be seen from table 6, the skin retention of the naftifine ketoconazole gels prepared in examples 1-4 (containing 0.8% naftifine hydrochloride and 0.125% ketoconazole) were similar to that of bifenthrin (containing 1% naftifine hydrochloride and 0.25% ketoconazole), indicating that the naftifine ketoconazole gels prepared according to the prescription and process of this patent (containing 0.8% naftifine hydrochloride and 0.125% ketoconazole) had similar clinical effects to that of bifenthrin (naftifine ketoconazole cream). The gel prepared in comparative example 1 and containing 1% naftifine hydrochloride and 0.25% ketoconazole has much higher skin retention than the clear gel, so that more active ingredients enter blood, and the risk of side effects is increased.
The foregoing description of specific embodiments of the present invention has been presented. It is to be understood that the present invention is not limited to the specific embodiments described above, and that various changes and modifications may be made by one skilled in the art within the scope of the appended claims without departing from the spirit of the invention.

Claims (10)

1. A gel composition is characterized in that the gel composition is a naftifine ketoconazole gel composition and comprises naftifine hydrochloride and ketoconazole active ingredients, a thickening agent, an emulsifying agent, a solubilizing agent, a solvent, an emollient, an antioxidant, a chelating agent, a pH regulator and water.
2. The gel composition of claim 1, wherein the active ingredients and the excipients are, in mass percent based on the total weight of the naftifine ketoconazole gel composition: 0.7-0.9% of naftifine hydrochloride, 0.1-0.2% of ketoconazole, 3-6% of thickening agent, 0.1-1% of emulsifying agent, 2-6% of solubilizer, 3-5% of solvent, 4-6% of emollient, 0.1-0.2% of antioxidant, 0.05-0.1% of chelating agent, and a proper amount of pH regulator and water.
3. The gel composition of claim 2, wherein the weight ratio of naftifine hydrochloride to ketoconazole is 6.4: 1.
4. the gel composition of claim 2, wherein the thickener is selected from the group consisting of acrylamide/sodium acryloyldimethyl taurate copolymers in a proportion of 3 to 6% by weight based on the total weight of the naftifine ketoconazole gel.
5. The gel composition of claim 2, wherein the emulsifier is selected from one or more of polyoxyethylene ether, tween 60 and docusate sodium, and is present in an amount of 0.1-1% by weight based on the total weight of the naftifine ketoconazole gel.
6. The gel composition of claim 2, wherein the solubilizer is selected from one or more of diethylene glycol monoethyl ether and polyethylene glycol glyceryl caprylate caprate, and is present in an amount of 2-6% by weight based on the total weight of the naftifine ketoconazole gel.
7. The gel composition of claim 2, wherein the emollient is selected from one or more of propylene glycol dipelargonate, dimethicone 350, and polyethylene glycol-7 cocoglyceride, and is present in a ratio of 4-6% by weight of the total naftifine ketoconazole gel.
8. The gel composition of claim 2, wherein the active ingredient and the adjuvant are, in mass percent based on the total weight of the gel composition: 0.7-0.9% of naftifine hydrochloride, 0.1-0.2% of ketoconazole, 4% of thickening agent, 0.2% of emulsifying agent, 3.5% of solubilizer, 4% of solvent, 5% of emollient, 0.1-0.2% of antioxidant, 0.05-0.1% of chelating agent, 74.60-86.95% of water and a proper amount of pH regulator.
9. A method of preparing a gel composition according to claim 2, comprising the steps of:
(1) preparing an active phase I: taking naftifine hydrochloride with the prescription amount, solubilizer with the prescription amount of 50 percent and solvent with the prescription amount of 50 percent, heating to 60-70 ℃ for dissolving for later use.
(2) Preparing an active phase II: taking ketoconazole with the prescription amount, solubilizer with the prescription amount of 50 percent and solvent with the prescription amount of 50 percent, heating to 40-50 ℃ for dissolving for later use.
(3) Preparation of gel matrix: taking the thickening agent according to the prescription amount, adding the water and the emulsifier according to the prescription amount at the temperature of 30-40 ℃, stirring and dispersing, adding the emollient chelating agent and the antioxidant according to the prescription amount after uniform dispersion, and stirring uniformly.
(4) Adding the active phase I into the mixture obtained in the step (3), uniformly stirring, and adjusting the pH value to 6.5-7.5 by using sodium hydroxide. And (3) after uniformly stirring, adding the active phase II, and uniformly stirring to obtain the naftifine ketoconazole gel.
10. Use of a naftifine ketoconazole gel composition according to any one of claims 1 to 8 for the preparation of a medicament for the treatment of fungal skin diseases.
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Citations (5)

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CN1481797A (en) * 2002-09-09 2004-03-17 重庆华邦制药股份有限公司 Composition comprising ketoconazole and sultifen
CN105342986A (en) * 2015-11-04 2016-02-24 吉林修正药业新药开发有限公司 Terbinafine hydrochloride gel and preparation method thereof
US20160067197A1 (en) * 2013-01-31 2016-03-10 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
CN108606967A (en) * 2018-04-19 2018-10-02 泮宝峰 A kind of Ketoconazol/Clobetasol Propionate topical composition
JP6591100B1 (en) * 2019-01-25 2019-10-16 ロート製薬株式会社 Pharmaceutical composition for nail and around nail

Patent Citations (5)

* Cited by examiner, † Cited by third party
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CN1481797A (en) * 2002-09-09 2004-03-17 重庆华邦制药股份有限公司 Composition comprising ketoconazole and sultifen
US20160067197A1 (en) * 2013-01-31 2016-03-10 Merz Pharmaceuticals, Llc Topical compositions and methods for making and using same
CN105342986A (en) * 2015-11-04 2016-02-24 吉林修正药业新药开发有限公司 Terbinafine hydrochloride gel and preparation method thereof
CN108606967A (en) * 2018-04-19 2018-10-02 泮宝峰 A kind of Ketoconazol/Clobetasol Propionate topical composition
JP6591100B1 (en) * 2019-01-25 2019-10-16 ロート製薬株式会社 Pharmaceutical composition for nail and around nail

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