Clobetasol + Clotrimazole Uses Show
How Clobetasol + Clotrimazole worksClobetasol + Clotrimazole is a combination of two medicines: Clobetasol and Clotrimazole which treat fungal skin infections. Clobetasol is a steroid which blocks the production of certain chemical messengers (prostaglandins) that make the skin red, swollen and itchy. Clotrimazole is an antifungal which stops the growth of fungi by preventing them from forming their own protective covering. Common side effects of Clobetasol + ClotrimazoleBurning sensation, Stinging sensation, Erythema (skin redness), Irritation, Itching The invention discloses ketoconazole and clobetasol propionate cream which comprises the following components in percentage by weight: 1-6 percent of ketoconazole, 0.1-2 percent of chlorhexidine acetate, 0.01-0.15 percent of clobetasol propionate, 0.1-5 percent of methyl
salicylate, 20-28 percent of a greasing base, 5-8 percent of a water-soluble base, 3-8 percent of an emulsifier, 3-6 percent of a cosolvent, 0.01-0.4 percent of an antioxidant, 0.1-1 percent of an essence and purified water in balancing amount. The ketoconazole and clobetasol propionate cream provided by the invention has the effects of fungus resistance, bacterium resistance and inflammation resistance and achieves a good transdermal effect. Ketoconazole and Clobetasol Propionate Cream and preparation method thereof Technical field The present invention relates to technical field of medicine, particularly relate to a kind of Ketoconazole and Clobetasol Propionate Cream and preparation method thereof. Background technology Fungal infection is divided into according to infection aspect: shallow table, subcutaneous and whole body, superficial fungal infection is the most common in clinic skin disease.Superficial fungal infection relates to the infection of epidermis, hair and first, is usually infected by sporidiole bacteria, Trichophyton, candidiasis and chlosma and causes. Ketoconazole is imidazoles two alkane derivatives of synthesis, has the
antifungic action of wide spectrum, especially has significantly antibacterial and bactericidal action to dermatophytosis, candidiasis and chlosma.Its mechanism of action is the biosynthesis by Antifungi cell membrane ergosterol, affects membrane passage and suppresses it to grow. But, fungal infection often with the existence of inflammation and antibacterial, the antifungal agent such as alone ketoconazole often poor effect, and further antibacterial or fungal infection are also easily
brought out in alone hormones antibiotic medicine. In addition, for the antifungal drug of superficial fungal infection, usually adopt the exterior-applied formulations such as ointment, there is the advantages such as untoward reaction is light, clinical application range is wide, but also there is the shortcomings such as transdermal effect is undesirable, bioavailability is low. Summary of the invention Based on this, be necessary, for the
problem existing for above-mentioned antifungal drug ointment, to provide one to have antifungal, antibacterium and antiinflammation, and the Ketoconazole and Clobetasol Propionate Cream that transdermal effect is good. A kind of Ketoconazole and Clobetasol Propionate Cream, comprise following component by weight percentage: ketoconazole 1 ~ 6%, chlorhexidine acetate 0.1 ~ 2%, clobetasol propionate 0.01 ~ 0.15%, methyl salicylate 0.1 ~ 5%, greasing base 20 ~ 28%, water-soluble base 5 ~ 8%,
emulsifying agent 3 ~ 8%, cosolvent 3 ~ 6%, antioxidant 0.01 ~ 0.4%, essence 0.1 ~ 1%, and the purified water of surplus. Wherein in an embodiment, described greasing base is selected from one or more the combination in white vaseline, liquid Paraffin, list (two) tristerin, octadecanol, cetostearyl alcohol, Cera Flava, methyl-silicone oil. Wherein in an embodiment, described water-soluble base is selected from one or more the combination in glycerol, sodium carboxymethyl cellulose,
Polyethylene Glycol, carbomer. Wherein in an embodiment, described emulsifying agent is selected from one or more the combination in sodium lauryl sulphate, Polysorbate, fatty alcohol-polyoxyethylene ether, Triton X-100. Wherein in an embodiment, described cosolvent is selected from one or more the combination in ethanol, dimethyl sulfoxide, propylene glycol. Wherein in an embodiment, described antioxidant is selected from one or more the combination in dibenzylatiooluene,
sodium sulfite, sodium sulfite, tocopherol, disodium edetate, 2,6-di-tert-butyl-4-methy phenols, gallic acid. Wherein in an embodiment, the pH value of described Ketoconazole and Clobetasol Propionate Cream is 6 ~ 8. The preparation method of Ketoconazole and Clobetasol Propionate Cream of the present invention, comprises the following steps: 1) get ketoconazole and clobetasol propionate, add in cosolvent, heated and stirred is dissolved; 2) get greasing base, heated and stirred melts, and then adds step 1) in the solution that obtains, stir, obtain oil mixture; 3) water-soluble substrate, adds chlorhexidine acetate, emulsifying agent, antioxidant and purified water, and heated and stirred is dissolved, and obtains aqueous mixture; 4) by step 3) aqueous mixture that obtains adds step 2) in the oil mixture that obtains, be uniformly mixed and obtain mastic, then with homogenizer, homogenizing is carried out to mastic, then add essence and methyl salicylate, continue to stir, obtain described Ketoconazole and Clobetasol Propionate Cream. Ketoconazole and Clobetasol Propionate Cream of the present invention has antifungal, antibacterium and antiinflammation, and wherein, ketoconazole has the antifungic action of wide spectrum; Chlorhexidine acetate is the antibacterial antibacterial of biguanides high-efficiency broad spectrum, all extremely sensitive to staphylococcus, streptococcus, Candida albicans, escherichia coli, anaerobism bacterium acidi propionici, itself and ketoconazole coupling, can expand antibacterial range, strengthen antibacterial curative effect; And clobetasol propionate is potent adrenal cortex swashs rope, there is stronger antiinflammatory, anti-allergic effects.In addition, Ketoconazole and Clobetasol Propionate Cream of the present invention is also added with methyl salicylate, and it has the effect of anti-inflammatory analgetic and sterilization, can also promote local blood circulation, improves tissue metabolism and the nutrition supply of diseased region, thus alleviates local pathological reaction.Transdermal absorption result shows, after having added methyl salicylate, the accumulative transdermal penetration amount of product is higher than the accumulative transdermal penetration amount not adding methyl salicylate, illustrate that methyl salicylate can promote that ketoconazole, chlorhexidine acetate and clobetasol propionate are in the absorption of skin, increase the effect of Drug Percutaneous Absorption, thus strengthen drug effect further. In Ketoconazole and Clobetasol Propionate Cream of the present invention, the amount ratio of ketoconazole is preferably 1 ~ 6%, and the amount ratio of clobetasol propionate is preferably 0.01 ~ 0.15%, if the consumption of ketoconazole and clobetasol propionate is too low, clinical effectiveness is bad; If the consumption of ketoconazole and clobetasol propionate is too high, results of animal display AST, ALT, blood glucose, cholesterol are all higher, and liver function can be caused to damage.The amount ratio of methyl salicylate is preferably 0.1 ~ 5%, if the consumption of methyl salicylate is too low, cannot produce the effect promoting Drug Percutaneous Absorption; If the consumption of methyl salicylate is too high, then can cause stimulation to skin. Ketoconazole and Clobetasol Propionate Cream of the present invention, its pH value is preferably 6 ~ 8, if pH value is too high, clobetasol propionate can be made degraded to occur and reduce drug effect; If pH value is too low, ketoconazole can be made degraded to occur and reduce drug effect. Detailed description of the invention Embodiment one: the preparation of Ketoconazole and Clobetasol Propionate Cream of the present invention Each component is taken respectively according to the formula of table 1: Table 1 Get the component in formula shown in table 1 respectively, according to following steps, prepare Ketoconazole and Clobetasol Propionate Cream of the present invention: 1) get ketoconazole and clobetasol propionate, add in cosolvent, be heated to 80 ± 5 DEG C, stir and make it to dissolve completely; 2) get greasing base, be heated to 85 ± 5 DEG C, stir and make it to melt completely, be incubated and be cooled to 80 ± 2 DEG C after 30 minutes, then add step 1) in the solution that obtains, stir, obtain oil mixture; 3) water-soluble substrate, adds chlorhexidine acetate, emulsifying agent, antioxidant and purified water, is heated to 90 ± 5 DEG C, stirs and makes it to dissolve completely, be incubated and be cooled to 80 ± 2 DEG C after 15 minutes, obtain aqueous mixture; 4) by step 3) aqueous mixture that obtains adds step 2) in the oil mixture that obtains, be uniformly mixed 30 minutes and obtain mastic, when mastic is cooled to 60 ~ 65 DEG C, with homogenizer, homogenizing is carried out 5 minutes to mastic, continue to be stirred to mastic temperature and drop to less than 42 DEG C, then add essence and methyl salicylate, continue to be stirred to mastic temperature and drop to less than 38 DEG C, obtain described Ketoconazole and Clobetasol Propionate Cream. Embodiment two: Transdermal absorption effect measuring 1, Ketoconazole and Clobetasol Propionate Cream reference examples is prepared 1) get 10g ketoconazole and 0.25g clobetasol propionate, add in 40g dimethyl sulfoxide, be heated to 80 ± 5 DEG C, stir and make it to dissolve completely; 2) 50g white vaseline, 65g liquid Paraffin, mono-(two) tristerin of 70g and 50g cetostearyl alcohol is got, be heated to 85 ± 5 DEG C, stirring makes it to melt completely, be incubated and be cooled to 80 ± 2 DEG C after 30 minutes, then step 1 is added) in the solution that obtains, stir, obtain oil mixture; 3) 50g Polyethylene Glycol is got, add 5g chlorhexidine acetate, 50g fatty alcohol-polyoxyethylene ether, 0.1g dibenzylatiooluene and 602.65g purified water, be heated to 90 ± 5 DEG C, stir and make it to dissolve completely, be incubated and be cooled to 80 ± 2 DEG C after 15 minutes, obtain aqueous mixture; 4) by step 3) aqueous mixture that obtains adds step 2) in the oil mixture that obtains, be uniformly mixed 30 minutes and obtain mastic, when mastic is cooled to 60 ~ 65 DEG C, with homogenizer, homogenizing is carried out 5 minutes to mastic, continue to be stirred to mastic temperature and drop to less than 42 DEG C, then add 2g essence, continue to be stirred to mastic temperature and drop to less than 38 DEG C, obtain Ketoconazole and Clobetasol Propionate Cream reference examples. 2, skin permeation test in vitro Adopt Transdermal Absorption test method(s), in vitro animal is done for examination skin with pig abdominal part skin, ethanol normal saline with 80% is as lipophilic permeation receiving liquid, the normal saline of 0.9% is hydrophilic osmotic receiving liquid, adopt high performance liquid chromatography (HPLC), detect the main constituent content in receiving liquid, calculate its accumulative transdermal penetration amount Q (μ g/cm 2), result is as shown in table 2 below. The skin permeation test in vitro result of table 2 Ketoconazole and Clobetasol Propionate Cream From the result of the test of table 2,36 hours transdermal penetration amounts of embodiment 1 are better than reference examples, show, by adding methyl salicylate, can promote the Transdermal absorption of Ketoconazole and Clobetasol Propionate Cream. Embodiment three: therapeutic effect measures 1, case selection: Get attached 3rd hospital's Dermatology & STD Dept. clinic case 114 example of Zhongshan Medical Univ.. Inclusion criteria: the dermatosis patient being diagnosed as tinea corporis and cruris, tinea manus and pedis, tinea versicolor, eczema, dermatitis, sex, age are not limit. Following case person does not list the object of observation in: (1) gestation and women breast-feeding their children; (2) treat the last fortnight or accepted radiotherapy in the recent period, systemic immune inhibitor or antibacterium, antiviral and anthelmintic medicine person; (3) treatment the last fortnight was used topical antifungal agents or was treated and took antifungal agent person orally in first 1 month; (4) allergies person is had to imidazoles; (5) liver, kidney or blood patient is had. 2, Therapeutic Method Clean affected part, Ketoconazole and Clobetasol Propionate Cream of the present invention is applied in affected part equably. Tinea corporis and cruris: 2 times on the one, 3 weeks courses for the treatment of; Tinea manus and pedis: 2 times on the one, 4 weeks courses for the treatment of; Tinea versicolor: 2 times on the one, 2 weeks courses for the treatment of; Eczema, dermatitis: 2 times on the one, 3 weeks courses for the treatment of. 3, observational technique (1), before patient treatment medication and drug withdrawal after a week, clinicing symptom observation is carried out respectively; (2) fungus microscope examination and cultivation; (3) untoward reaction after recording medicine. 4, curative effect judging standard (1) clinical efficacy criterion Recovery from illness: erythra disappears completely, gargalesthesia disappears, and fungal culture is negative. Effective: deflorescence more than 60%, gargalesthesia obviously alleviates, and negative fungal examination or visible a small amount of broken, the mycelia of distortion, spore, cultivate negative. Progressive: deflorescence 20 ~ 60%, gargalesthesia alleviates, positive for fungi culture. Invalid: deflorescence is less than 20% or continue to increase the weight of, gargalesthesia is the same or aggravate, positive for fungi culture. Recovery from illness and effectively add up to effectively, calculating effective percentage. (2) mycology curative effect judging standard Mycology curative effect is removed (negative fungal examination) according to fungus and is not removed (fungus microscope examination is positive) statistics. Fungus microscope examination is positive: visible fungus under microscope; Negative fungal examination: have no fungus under microscope. 5, therapeutic effect In 114 routine patients, complete 112 examples of the regulation course for the treatment of, enter 112 examples of therapeutic evaluation.Wherein, tinea corporis and cruris 39 example, tinea manus and pedis 28 example, tinea versicolor 8 example, eczema 12 example, seborrheic dermatitis 16 example, contact dermatitis 9 example. In clinical trial process, all there is not the toxic and side effects reaction caused by Ketoconazole and Clobetasol Propionate Cream of the present invention. Table 3 is the clinical efficacy test result of Ketoconazole and Clobetasol Propionate Cream of the present invention, and its average cure rate is 83.93%, and average effectiveness level is 91.96%. The clinical efficacy test result of table 3 Ketoconazole and Clobetasol Propionate Cream
* effective percentage=effectively number of cases ÷ number of cases; Average cure rate=recovery from illness number of cases ÷ total cases. Carry out fungal culture (by standards of pharmacopoeia method) before 114 routine patient treatments, wherein 67 examples are positive in fungus microscope examination.Table 4 is the mycology curative effect test result of Ketoconazole and Clobetasol Propionate Cream of the present invention, and the average negative conversion rate after its treatment is 88.06%. The mycology curative effect test result of table 4 Ketoconazole and Clobetasol Propionate Cream
* positive number of cases before negative conversion rate=(before treatment the rear positive number of cases of positive number of cases-treatment) ÷ treatment. 6, conclusion Clinical trial proves, tinea corporis and cruris, tinea manus and pedis, tinea versicolor and eczema that Ketoconazole and Clobetasol Propionate Cream of the present invention causes treatment superficial mycosis, dermatitis all have good therapeutic effect, cure rate is 83.93%, and effective percentage is 91.96%, and fungus negative conversion rate is 88.06%.Over the course for the treatment of to the side effect such as skin is all non-stimulated, irritated reaction, can be used as the external used medicine of the mycotic infection of superficial part such as treatment tinea, eczema, dermatitis. The above embodiment only have expressed several embodiment of the present invention, and it describes comparatively concrete and detailed, but therefore can not be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that for the person of ordinary skill of the art, without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims. Claims (8)1. a Ketoconazole and Clobetasol Propionate Cream, comprise following component by weight percentage: ketoconazole 1 ~ 6%, clobetasol propionate 0.01 ~ 0.15%, methyl salicylate 0.1 ~ 5%, chlorhexidine acetate 0.1 ~ 2%, greasing base 20 ~ 28%, water-soluble base 5 ~ 8%, emulsifying agent 3 ~ 8%, cosolvent 3 ~ 6%, antioxidant 0.01 ~ 0.4%, essence 0.1 ~ 1%, and the purified water of surplus. 2. Ketoconazole and Clobetasol Propionate Cream according to claim 1, is characterized in that: described greasing base is selected from one or more the combination in white vaseline, liquid Paraffin, list (two) tristerin, octadecanol, cetostearyl alcohol, Cera Flava, methyl-silicone oil. 3. Ketoconazole and Clobetasol Propionate Cream according to claim 1, is characterized in that: described water-soluble base is selected from one or more the combination in glycerol, sodium carboxymethyl cellulose, Polyethylene Glycol, carbomer. 4. Ketoconazole and Clobetasol Propionate Cream according to claim 1, is characterized in that: described emulsifying agent is selected from one or more the combination in sodium lauryl sulphate, Polysorbate, fatty alcohol-polyoxyethylene ether, Triton X-100. 5. Ketoconazole and Clobetasol Propionate Cream according to claim 1, is characterized in that: described cosolvent is selected from one or more the combination in ethanol, dimethyl sulfoxide, propylene glycol. 6. Ketoconazole and Clobetasol Propionate Cream according to claim 1, it is characterized in that: described antioxidant is selected from one or more the combination in dibenzylatiooluene, sodium sulfite, sodium sulfite, tocopherol, disodium edetate, 2,6-di-tert-butyl-4-methy phenols, gallic acid. 7. according to claim 1 to 6 one of them described in Ketoconazole and Clobetasol Propionate Cream, it is characterized in that: the pH value of described Ketoconazole and Clobetasol Propionate Cream is 6 ~ 8. 8. the preparation method of Ketoconazole and Clobetasol Propionate Cream according to claim 1, comprises the following steps: 1) get ketoconazole and clobetasol propionate, add in cosolvent, heated and stirred is dissolved; 2) get greasing base, heated and stirred melts, and then adds step 1) in the solution that obtains, stir, obtain oil mixture; 3) water-soluble substrate, adds chlorhexidine acetate, emulsifying agent, antioxidant and purified water, and heated and stirred is dissolved, and obtains aqueous mixture; 4) by step 3) aqueous mixture that obtains adds step 2) in the oil mixture that obtains, be uniformly mixed and obtain mastic, then with homogenizer, homogenizing is carried out to mastic, then add essence and methyl salicylate, continue to stir, obtain described Ketoconazole and Clobetasol Propionate Cream. Priority Applications (1)
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What can clobetasol propionate be used for?Clobetasol topical is used to help relieve redness, itching, swelling, or other discomfort caused by certain skin conditions.
What is the difference between clotrimazole and clobetasol?Clobetasol is a steroid which blocks the production of certain chemical messengers (prostaglandins) that make the skin red, swollen and itchy. Clotrimazole is an antifungal which stops the growth of fungi by preventing them from forming their own protective covering.
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Can clobetasol propionate be used for fungal infection
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