CN106727281B - Compound external preparation for treating fungal infection and preparation method and application thereof - Google Patents
Compound external preparation for treating fungal infection and preparation method and application thereof Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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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
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- 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
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
- A61K47/30—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
- 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
Abstract
The invention relates to a compound external preparation for treating fungal infection and a preparation method and application thereof, belonging to the technical field of traditional Chinese medicine preparations. The compound external preparation contains the following substances: terbinafine hydrochloride, mometasone furoate, carbomer 940NF, triethanolamine, ethanol, polyethylene glycol-400, propylene glycol, polysorbate 80, dimethyl sulfoxide, disodium ethylene diamine tetraacetate and the balance of distilled water. The invention has the following advantages: (1) can quickly penetrate the cuticle, has the characteristics of quickly relieving itching, controlling local erythema pimple and the like and promoting the improvement of inflammatory reaction, and solves the problem of clinical combined medication; (2) the compound emulsifiable paste is a water-soluble gel, can quickly act on a focus, has the advantages of good transdermal absorption, cleanness, sanitation and the like, and solves the problems that the compound emulsifiable paste preparation sold in the market is not suitable for being uniformly smeared and pollutes clothes and the like.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a compound external preparation for treating fungal infection and a preparation method and application thereof.
Background
Superficial mycosis is a group of diseases caused by infection of superficial tissues such as human skin, hair and nail plate by pathogenic fungi such as dermatophyte and pathogenic yeast or conditionally pathogenic fungi, and accounts for the first of skin infectious diseases. With the wide application of broad-spectrum antibiotics and glucocorticoids, and the change of personnel mobility and environment, the incidence rate of superficial mycosis is on a trend of increasing day by day, and the recurrence rate can reach 15%, which seriously affects the health and life of human beings.
The antifungal medicine for external use is mainly allylamines represented by terbinafine and butenafine and azole medicines represented by clotrimazole, ketoconazole and econazole nitrate. In recent years, a compound external preparation prepared by combining an antifungal medicament and glucocorticoid is published in the field of dermatology, has the characteristics of quickly relieving itching, controlling local erythema and pimple and the like and promoting improvement of inflammatory response, is mainly used for treating acute superficial fungal infection accompanied by obvious inflammatory response and is also suitable for dermatitis and eczema diseases of secondary fungal infection, and typical medicaments are triamcinolone acetonide econazole cream and compound clotrimazole cream. The ointment is easy to cause uneven coating and pollute clothes, and the gel has the characteristics of convenient use, cleanness, sanitation, good skin absorption, stability, uniformity and beautiful dosage form.
Disclosure of Invention
Terbinafine can inhibit single fungal enzyme, squalene epoxidase, and thus has inhibiting and killing effect on fungi, and pharmacodynamics research results show that domestic and imported terbinafine have equivalent antibacterial effect and are superior to ketoconazole. Terbinafine is metabolized by the extensive liver and is mainly cleared from urine (about 80%), the total plasma clearance rate is 75%/h, the plasma clearance half-life is 11 to 16 hours, and its pharmacokinetics are the same in the elderly and in the young. Mommi furoate is a glucocorticoid used locally, has the functions of anti-inflammation, anti-allergy and the like, and is characterized in that the action intensity is increased and the side effect is increased disproportionately. The terbinafine hydrochloride and the mometasone furoate are jointly applied, and the prepared compound external preparation can quickly penetrate through the stratum corneum to play the antibacterial and anti-inflammatory effects, does not cause adverse reactions of skin and the whole body, is safer to apply, and is worthy of clinical popularization and application.
The invention aims to disclose a compound external preparation for treating fungal infection.
The invention also aims to disclose the application of the compound external preparation for treating fungal infection in preparing the medicine for treating fungal infection.
The third purpose of the invention is to disclose a preparation method of the compound external preparation for treating fungal infection.
The fourth purpose of the invention is to disclose the application of the compound external preparation prepared by the preparation method in preparing the medicine for treating fungal infection.
The purpose of the invention is realized by the following technical scheme:
a compound external preparation for treating fungal infection is prepared from the following substances in parts by weight: 50-150 parts of terbinafine hydrochloride, 2.5-15 parts of mometasone furoate, 120-150 parts of carbomer 940NF, 50-80 parts of triethanolamine, 2850-3050 parts of ethanol, 400950-1050 parts of polyethylene glycol, 1950-2050 parts of propylene glycol, 300-400 parts of polysorbate 80300, 450-600 parts of dimethyl sulfoxide, 5-15 parts of disodium ethylenediamine tetraacetic acid and 2600-2800 parts of distilled water.
The compound external preparation for treating fungal infection according to the technical scheme is composed of the following substances by weight: 100g of terbinafine hydrochloride, 5g of mometasone furoate, 940NF 150g of carbomer, 80g of triethanolamine, 3000g of ethanol, 4001000 g of polyethylene glycol-4001000 g, 2025g of propylene glycol, 80400 g of polysorbate, 500g of dimethyl sulfoxide, 10g of disodium ethylenediamine tetraacetate and 2730g of distilled water.
The application of the compound external preparation for treating fungal infection in the preparation of the medicine for treating fungal infection is provided.
A preparation method of a compound external preparation for treating fungal infection is characterized by comprising the following steps: the preparation method comprises the following steps:
(1) weighing the raw materials in the technical scheme;
(2) sequentially adding polyethylene glycol-400 and propylene glycol into carbomer 940NF, and stirring;
(3) dissolving polysorbate 80 in 2400ml of distilled water, uniformly mixing, adding into the liquid obtained in the step (2), uniformly stirring, and swelling overnight;
(4) dissolving triethanolamine and disodium ethylene diamine tetraacetate in 330ml of distilled water, adding the liquid obtained in the step (3), and stirring uniformly to obtain a gel matrix for later use;
(5) weighing 30% ethanol in parts by weight of ethanol; dissolving terbinafine hydrochloride in 30% ethanol, gradually adding into the gel matrix obtained in step (4), and stirring;
(6) weighing 70% ethanol in parts by weight of ethanol; dissolving mometasone furoate in 70% ethanol and dimethyl sulfoxide, gradually adding into the product obtained in step (5), and stirring to obtain a compound external preparation for treating fungal infection.
The compound external preparation prepared by the preparation method according to the technical scheme is applied to preparing a medicine for treating fungal infection.
The using method comprises the following steps: the product is topically applied to affected part and its periphery for 2 times a day. Continuously using tinea corporis and tinea cruris for 2-4 weeks; the medicine is continuously applied for 4-6 weeks for tinea manuum, tinea pedis and tinea versicolor.
The invention has the following beneficial effects:
1. the compound terbinafine hydrochloride gel is a compound external preparation prepared by combining antifungal drugs and glucocorticoids, can quickly penetrate through cuticle, plays the roles of antibiosis and antiphlogosis, has the characteristics of quickly relieving itching, controlling local erythema and pimple and the like and promoting the improvement of inflammatory response, is mainly used for treating acute superficial fungal infection accompanied with obvious inflammatory response, is also suitable for dermatitis and eczema diseases of secondary fungal infection, does not cause adverse reactions of skin and the whole body, is safer to apply, and solves the problem of clinical combined medication.
2. The compound terbinafine hydrochloride gel is a water-soluble gel, is a semi-solid preparation with a transparent to semitransparent shape, can quickly act on a focus, has the advantages of good transdermal absorption, cleanness, sanitation and the like, and solves the problems that the compound emulsifiable paste preparation sold in the market is not suitable for being uniformly smeared and pollutes clothes and the like.
The specific implementation mode is as follows:
in order to facilitate understanding of the technical scheme of the invention, the preparation method of the compound external preparation for treating fungal infection (hereinafter, referred to as compound terbinafine hydrochloride gel) of the invention is further described with reference to specific examples.
Example 1:a compound external preparation for treating fungal infection is prepared by the following steps:
(1) weighing the following raw material medicines by weight: 100g of terbinafine hydrochloride, 5g of mometasone furoate, 940NF 150g of carbomer, 80g of triethanolamine, 3000g of ethanol, 4001000 g of polyethylene glycol-4001000 g, 2025g of propylene glycol, 80400 g of polysorbate, 500g of dimethyl sulfoxide, 10g of disodium ethylenediamine tetraacetate and 2730g of distilled water;
(2) sequentially adding polyethylene glycol-400 (PEG-400) and Propylene Glycol (PG) into carbomer 940NF, and stirring;
(3) dissolving polysorbate 80(Tween-80) in 2400ml of distilled water, uniformly mixing, adding into the liquid obtained in the step (2), uniformly stirring, and swelling overnight;
(4) dissolving Triethanolamine (TEOA) and disodium ethylene diamine tetraacetate (EDTA-2Na) in 330ml of distilled water, adding the liquid obtained in the step (3), and stirring uniformly to obtain a gel matrix for later use;
(5) weighing 900g of ethanol from 3000g of ethanol; dissolving terbinafine hydrochloride in 900g of ethanol, gradually adding into the gel matrix obtained in the step (4), and stirring;
(6) weighing 2100g of ethanol from 3000g of ethanol; dissolving mometasone furoate in 2100g of ethanol and dimethyl sulfoxide (DMSO), gradually adding into the product obtained in the step (5), and stirring; the compound external preparation for treating fungal infection is obtained, and the weight is 10000 g.
When the compound terbinafine hydrochloride gel is used, 1000 pieces of the compound external preparation prepared in the example 1 are filled in an aluminum tube, and the compound terbinafine hydrochloride gel can be used.
Example 2:the optimal composition proportion of the two raw material medicines in the compound preparation is determined:
step one, the proportion of terbinafine hydrochloride (TBNF) components is unchanged, and the influence of different component proportions of Mometasone Furoate (MF) on the curative effect is examined.
According to literature and similar medicines sold in markets, the component proportion of terbinafine hydrochloride in different dosage forms is 1%, so that the component proportion of terbinafine hydrochloride is temporarily determined to be 1%, and the component proportion of mometasone furoate in the compound gel preparation is investigated. In order to determine the proportion and the effect of the mometasone furoate in the preparation, a terbinafine hydrochloride gel group is added. The composition of the main components of mometasone furoate in each group is 0.125%, 0.1%, 0.05%, 0.025% and 0%, and the composition is used for treating the dermatophytosis of guinea pigs infected by trichophyton mentagrophytes, and the results are shown in Table 1.
TABLE 1 evaluation of the efficacy of the compound terbinafine hydrochloride gel of mometasone furoate with different component ratios on the treatment of trichophyton mentagrophytes infected animals (
n＝9)
Note: in comparison with the group C,△shows that the two groups of curative effect scores have significant difference, P<0.05；△△Shows that the two groups of curative effect scores are compared and have extremely significant difference, P<0.01。
And (4) conclusion: the results of the treatment of local infection of guinea pig with the compound terbinafine hydrochloride gel of mometasone furoate with different component proportions show that the ratio of the components in the gel is 1%: 0.05% group to 1%: the 0.1% group is superior in efficacy to the other groups, and there is no significant difference between the two groups, and 1% is preferable in view of safety of long-term use of glucocorticoid: 0.05% group.
And step (II), determining that the component proportion of mometasone furoate is 0.05% by the experiment, and further investigating the influence of different component proportions of terbinafine hydrochloride on the curative effect. The proportion of the main components of the composition containing terbinafine hydrochloride is 1.5%, 1% and 0.5%, and the composition is used for treating the dermatophytosis of guinea pigs infected by trichophyton mentagrophytes, and the results are shown in Table 2.
TABLE 2 hydrochloric acid of different component ratiosEvaluation of efficacy of terbinafine hydrochloride gel for treating animals infected with Trichophyton mentagrophytes (terbinafine hydrochloride) ((
n＝9)
Note: in comparison with the group C,△shows that the two groups of curative effect scores have significant difference, P<0.05；△△Shows that the two groups of curative effect scores are compared and have extremely significant difference, P<0.01。
And (4) conclusion: the treatment results of the compound terbinafine hydrochloride gel of terbinafine hydrochloride with different component proportions on the local infection trichophyton mentagrophytes of guinea pigs show that the curative effect scores of the E group (1.5%: 0.05%) and the C group (1%: 0.05%) have no significant difference, and considering the side effect of antifungal drugs, the compound terbinafine hydrochloride gel is preferably 1%: 0.05% group.
The optimum composition proportion of the raw material medicaments of the product is determined by the test as follows: each gram contains 10mg of terbinafine hydrochloride and 0.5mg of mometasone furoate.
Example 3:determination of the preparation process:
solvent process selection of main drug
Terbinafine hydrochloride gel developed by the hospital belongs to an aqueous homogeneous semi-solid preparation under the terms of gel of the four-part general rule (0114) of Chinese pharmacopoeia 2015 edition, according to the prescription and the preparation types, the terbinafine hydrochloride is easy to dissolve in ethanol, is slightly soluble in water and is hardly soluble in ether, mometasone furoate is dissolved in dichloromethane and acetone, is slightly soluble in ethanol and is insoluble in water, dimethyl sulfoxide is added in the prescription to be used as a solvent of the terbinafine hydrochloride and mometasone furoate, and in the process of technological research, the ethanol and the dimethyl sulfoxide with the prescription amount can meet the dissolution of the terbinafine hydrochloride and mometasone furoate with the prescription amount, so the ethanol and the dimethyl sulfoxide are selected as solvents of medicines.
(II) selecting the adding mode of the main drug
In the preparation process, the invention discovers that if the ethanol solution of the main drug is added with carbomer firstly and then triethanolamine is used for adjusting the pH value, the main drug sometimes can be separated out, probably because the main drug can react with the main drug when the triethanolamine (medium-strength alkali) is added for adjusting the pH value; however, if the pH value is adjusted by using triethanolamine and then the ethanol solution of the main drug is added, the phenomenon of main drug precipitation still occurs, probably because the mometasone furoate is slightly soluble in ethanol, so the invention adopts a mode that the mometasone furoate is dissolved in dimethyl sulfoxide with the prescription amount and ethanol with 70% of the prescription amount, the terbinafine hydrochloride is dissolved in ethanol with 30% of the prescription amount, and the gel matrix is sequentially and slowly added to prepare the compound terbinafine hydrochloride gel.
The results of influencing factor tests, acceleration tests and long-term tests show that: the product is stable according to the prescription of general hospitals of air force and samples produced according to the process of the hospital, and has basically the same gel-like properties as terbinafine hydrochloride in the hospital.
The product is subjected to accelerated test and long-term test according to the regulations of the four parts of the Chinese pharmacopoeia 2015 year edition, so as to provide basis for the production, packaging, storage and transportation conditions of the medicine, and the effective period of the medicine is determined through the test.
(III) accelerated test:
the packaged sample is placed at 40 ℃ plus or minus 2 ℃ and relative humidity of 75 percent plus or minus 5 percent for 6 months. Samples were taken at the end of 0, 1, 2, 3, and 6 months for each examination.
As a result: three batches of amplified samples of the product are inspected for 6 months through accelerated tests, the appearance, the uniformity, the related substances, the content and the like of the samples have no obvious change, and the microbial limit inspection conforms to the regulations, which are shown in Table 3. Accelerated test and long-term test show that the product has good stability.
Detecting items: traits, related substances, assay and microbial limits.
TABLE 3 accelerated test results
(IV) long-term test:
the packaged sample is placed at 25 ℃ plus or minus 2 ℃ and relative humidity of 60 percent plus or minus 10 percent for 36 months. Samples were taken at the end of months 0, 3, 6, 9, 12, 18, 24, 36 for each examination. As a result: after long-term test and investigation of three batches of amplified samples of the product for 24 months, the appearance, the uniformity, the related substances, the content and the like of the samples have no obvious change, and the microbial limit inspection conforms to the regulations. The stability of the product is good. The results are shown in Table 4.
TABLE 4 Long term stability test
Accelerated test shows that the product is placed for 6 months under the conditions of packaging in the market and 40 ℃ and 75% of relative humidity, and all indexes meet the quality standard. Long-term test shows that the product is placed for 24 months under the long-term test condition, and all indexes are basically unchanged.
The following pharmacodynamic experiment of the compound external preparation for treating fungal infection prepared in the embodiment 1 of the invention illustrates the beneficial effects of the invention:
experimental example 1:pharmacodynamic test data:
in conclusion, the compound terbinafine hydrochloride gel component preferably contains 10mg of terbinafine hydrochloride per gram and 0.5mg of mometasone furoate. The compound terbinafine hydrochloride gel, the triamcinolone acetonide econazole cream and the mometasone furoate gel are respectively used for treating a skin ringworm infected guinea pig model, the dosage of each infected area is 0.2g, 2 times per day and 3 weeks continuously. Lesions were observed daily and evaluated on days 0, 8, 14, 18, 21 of treatment. The evaluation content comprises skin lesion and mycology examination, and skin tissues are taken for pathological detection and culture. The recurrence rate was calculated one week after withdrawal.
TABLE 5 curative ratio of compound terbinafine hydrochloride gel on cavy skin infection trichophyton mentagrophytes and microsporum canis mycology
TABLE 6 evaluation of the efficacy of compound terbinafine hydrochloride gel for treating trichophyton mentagrophytes-infected animals (
n＝9)
Note: group H is compound terbinafine hydrochloride gel, group K is triamcinolone acetonide econazole cream, group L is terbinafine hydrochloride gel, group M is 0.05% mometasone furoate gel, group N is excipient group, and group O is blank control group
In table 6, compared to group H, Δ indicates significant difference between the two groups of efficacy scores, P < 0.05; Δ represents a significant difference in the two groups of efficacy scores with P < 0.01. In comparison to group N, # denotes P > 0.05.
As can be seen from tables 5 and 6, the compound terbinafine hydrochloride has better curative effect than terbinafine hydrochloride gel (P <0.05) and triamcinolone acetonide econazole cream (P <0.01) in treating dermatophytosis of trichophyton mentagrophytes infected guinea pigs.
TABLE 7 evaluation of the efficacy of compound terbinafine hydrochloride gel for treating animals infected with microsporidian canis ((R))
n＝9)
Note: (P) is compound terbinafine hydrochloride gel group, (Q) is terbinafine hydrochloride gel, (R) is triamcinolone acetonide econazole cream, (S) 0.05% mometasone furoate gel
In table 7, compared to group P, Δ indicates significant difference between the two groups of efficacy scores, P < 0.05; Δ represents a significant difference in the two groups of efficacy scores with P < 0.01. In contrast to group Q, t χ represents P < 0.05.
As can be seen from Table 7, the compound terbinafine hydrochloride is most effective in treating dermatophytosis of guinea pig infected with microsporum canis.
And (3) knotting: the results of the compound terbinafine hydrochloride gel on the local infection of the skin of the guinea pig with the trichophyton mentagrophytes and the microsporum canis show that the curative effect of the compound terbinafine hydrochloride gel in 1-3 weeks is obviously superior to that of triamcinolone acetonide econazole cream and mometasone furoate gel (P <0.01), and the relapse rate is low after the compound terbinafine hydrochloride gel is stopped for one week.
Compared with the terbinafine hydrochloride gel group, in the aspect of evaluation of apparent curative effect, the compound terbinafine hydrochloride gel has better curative effect (P <0.05) in 8-18 days when the compound terbinafine hydrochloride gel is used for treating trichophyton mentagrophytes infected with guinea pig dermatomycosis, and has better curative effect (P <0.05) in 14 days and 18 days when the compound terbinafine hydrochloride gel is used for treating the microsporum canis infected with guinea pig dermatomycosis. The results are shown in tables 8 and 9 for the evaluation of the pathological effect.
TABLE 8 pathological results of 3 weeks of administration of Trichophyton mentagrophytes infected with Guinea pig skin
TABLE 9 pathological results of 3 weeks of administration of Trichophyton mentagrophytes infected with Guinea pig skin
In summary, the following steps: the compound terbinafine hydrochloride gel has obviously better curative effect than the terbinafine hydrochloride gel in treating the local infection of trichophyton mentagrophytes and microsporum canis to guinea pig mycosis.
And (4) conclusion: the compound terbinafine hydrochloride gel has the best curative effect on treating the local infection of trichophyton mentagrophytes and microsporum canis to guinea pig mycosis.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims; meanwhile, any equivalent changes, modifications and variations of the above embodiments according to the essential technology of the present invention are within the scope of the technical solution of the present invention.
Claims (4)
1. The compound external preparation for treating fungal infection is characterized by comprising the following substances in parts by weight: 100g terbinafine hydrochloride, 5g mometasone furoate, 150g carbomer 940NF, 80g triethanolamine, 3000g ethanol, 1000g polyethylene glycol-400, 2025g propylene glycol, 400g polysorbate 80, 500g dimethyl sulfoxide, 10g disodium ethylenediamine tetraacetate and 2730g distilled water;
the compound external preparation is prepared by the following steps:
(1) weighing the raw materials;
(2) sequentially adding polyethylene glycol-400 and propylene glycol into carbomer 940NF, and stirring;
(3) dissolving polysorbate 80 in 2400ml of distilled water, uniformly mixing, adding into the liquid obtained in the step (2), uniformly stirring, and swelling overnight;
(4) dissolving triethanolamine and disodium ethylene diamine tetraacetate in 330ml of distilled water, adding the liquid obtained in the step (3), and stirring uniformly to obtain a gel matrix for later use;
(5) weighing 30% ethanol in parts by weight of ethanol; dissolving terbinafine hydrochloride in 30% ethanol, gradually adding into the gel matrix obtained in step (4), and stirring;
(6) weighing 70% ethanol in parts by weight of ethanol; dissolving mometasone furoate in 70% ethanol and dimethyl sulfoxide, gradually adding into the product obtained in step (5), and stirring to obtain a compound external preparation for treating fungal infection.
2. The use of the compound external preparation for treating fungal infection according to claim 1 in the preparation of a medicament for treating fungal infection.
3. A preparation method of a compound external preparation for treating fungal infection is characterized by comprising the following steps: the preparation method comprises the following steps:
(1) weighing the raw materials of claim 1;
(2) sequentially adding polyethylene glycol-400 and propylene glycol into carbomer 940NF, and stirring;
(3) dissolving polysorbate 80 in 2400ml of distilled water, uniformly mixing, adding into the liquid obtained in the step (2), uniformly stirring, and swelling overnight;
(4) dissolving triethanolamine and disodium ethylene diamine tetraacetate in 330ml of distilled water, adding the liquid obtained in the step (3), and stirring uniformly to obtain a gel matrix for later use;
(5) weighing 30% ethanol in parts by weight of ethanol; dissolving terbinafine hydrochloride in 30% ethanol, gradually adding into the gel matrix obtained in step (4), and stirring;
(6) weighing 70% ethanol in parts by weight of ethanol; dissolving mometasone furoate in 70% ethanol and dimethyl sulfoxide, gradually adding into the product obtained in step (5), and stirring to obtain a compound external preparation for treating fungal infection.
4. The use of the compound external preparation prepared by the preparation method of claim 3 in the preparation of a medicament for treating fungal infection.
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| CN102292080A (en) * | 2009-01-21 | 2011-12-21 | 苏鲁·苏布拉马尼·瓦南加穆迪 | Novel dermaceutical cream made using Sodium Fusidate, antifungals and steroids |
| CN103402510A (en) * | 2010-12-20 | 2013-11-20 | 安德鲁·图安·安·勒 | Composition for the treatment of skin conditions |
| WO2014036165A1 (en) * | 2012-08-29 | 2014-03-06 | Bayer Healthcare, Llc | Aqueous based compositions for treating otitis externa |
| JP2015205877A (en) * | 2014-04-08 | 2015-11-19 | 株式会社ポーラファルマ | External pharmaceutical composition containing antifungal agent and steroid agent |
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| US7618651B2 (en) * | 2004-06-24 | 2009-11-17 | Idexx Laboratories | Pharmaceutical compositions for drug delivery and methods of treating or preventing conditions using same |
| CN1813697A (en) * | 2005-12-08 | 2006-08-09 | 咸阳步长医药科技发展有限公司 | Terbinafine hydrochloride vagina gel, and its preparing and quality control method |
| CN104771405A (en) * | 2015-03-16 | 2015-07-15 | 中国人民解放军第二军医大学 | Compound terbinafine preparation and applications thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102292080A (en) * | 2009-01-21 | 2011-12-21 | 苏鲁·苏布拉马尼·瓦南加穆迪 | Novel dermaceutical cream made using Sodium Fusidate, antifungals and steroids |
| CN103402510A (en) * | 2010-12-20 | 2013-11-20 | 安德鲁·图安·安·勒 | Composition for the treatment of skin conditions |
| WO2014036165A1 (en) * | 2012-08-29 | 2014-03-06 | Bayer Healthcare, Llc | Aqueous based compositions for treating otitis externa |
| JP2015205877A (en) * | 2014-04-08 | 2015-11-19 | 株式会社ポーラファルマ | External pharmaceutical composition containing antifungal agent and steroid agent |
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