CN1254242C - Anti-infectious medicine composition and pharmaceutical use thereof - Google Patents
Anti-infectious medicine composition and pharmaceutical use thereof Download PDFInfo
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- CN1254242C CN1254242C CN 200310100579 CN200310100579A CN1254242C CN 1254242 C CN1254242 C CN 1254242C CN 200310100579 CN200310100579 CN 200310100579 CN 200310100579 A CN200310100579 A CN 200310100579A CN 1254242 C CN1254242 C CN 1254242C
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- hibitane
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a medical composition used for treating infection by treponema pallidum, tinea unguium, dermatophytosis, and multiplicity of infection of fungi and bacteria, and application thereof. The composition is prepared from antimycotic ingredients and anti-bacterium ingredients in a synergy mode. The composition especially contains bifonazole and chlorhexidine. The medical composition provided by the present invention can be used as medicine for external use. Compared with the scope of treatment of common antimicrobial for external use, the scope of treatment is wide. The medical composition is clinically applied to treat infectious diseases, such as shallow fungi of the skin, bacterial infection, infection by treponema pallidum, tinea unguium, dermatophytosis, etc. The medical composition has the characteristics of high therapeutic effect, low relapse rate, low toxicity, etc.
Description
Technical field
The present invention relates to the pharmaceutical field anti-infective medicament composition, be particularly related to a kind of Compositional type anti-infective medicament composition, it has collaborative enhanced antibiotic effect, more can effectively treat diseases such as infection by Treponema pallidum, tinea unguium, beriberi and fungus and antibacterial MOI.
Background technology
Superficial skin fungus infects and bacterial infection is a kind of commonly encountered diseases and frequently-occurring disease, reaches 70% in the regional prevalence of sanitary condition difference, treats the double infection that the incident meeting of disadvantageous words is fungus and antibacterial (also claiming MOI in the clinical diagnosis).Though the anti-infective medicine is a lot of at present, it generally all is the one pack system medicine, most just to anti-fungal infection or bacterial infection, as known bifonazole is the anti-fungal infection medicine, hibitane is a bacterial-infection resisting medicine, and above two kinds of medicines are relatively poor to the MOI effect, other antibacterials such as econazole, chlortetracycline, ketoconazole, clotrimazole, miconazole, amoxicillin etc., wherein some is to claim broad-spectrum antiseptic, but no matter in the treatment is at fungal infection or bacterial infection, effect is all undesirable, and is especially invalid substantially concerning MOI.Clinical manifestation is not thorough to the treatment of the shallow fungal infection of skin table, and often recurrence is especially invalid especially to refractory infection such as the MOI of fungus and antibacterial, infection by Treponema pallidum, tinea unguium, beriberi.So at the medicine of anti-MOI, prior art is still blank.
Except compound infection, a lot of refractory infection diseases, for example common infection by Treponema pallidum, tinea unguium etc. are not all also thoroughly conquered by the mankind.Infection by Treponema pallidum belongs to the fungal infection disease, because treponema pallidum artificial culture problem is still unresolved so far, does not therefore also have a kind of specific drug can resist infection by Treponema pallidum, clinical most employing penicillin treatment, curative effect is not really desirable, treats not thoroughly, and disease recurs easily; Tinea unguium belongs to fungal infection, and its disease is extremely obstinate, uses existing antifungal drug that it is treated, and curative effect is very little; General medicine thinks that beriberi also belongs to the disease of fungal infection type, in fact owing to reason such as in-shoe environment permeability difference and sanitary condition be bad, beriberi is developed to the later stage and also mixes bacterial infection is arranged, therefore the beriberi initial stage is a fungal infection, the beriberi later stage also should belong to the category of MOI, this also is that the course of disease of beriberi is long, the main cause of outbreak very easily repeatedly after the treatment.So we can say, the just most at utmost relief of symptoms that medical circle can be done above-mentioned disease patient, the medical procedure of employing also is based on antifungal or antibacterium treatment at disease.
In fact, locate specific aim than strong except the medical science of fungal infection such as infection by Treponema pallidum, tinea unguium, a lot of infection all belong to MOI.This disease is more common in army, many antifungal drugs have been studied for many years both at home and abroad, but because of its to many-sided reasons such as double infection weak curative effect, drug toxicity, stability and synthesis techniques, clinical use is subjected to very big restriction, therefore, with regard to the Medical Technology in present diagnosis and treatment stage, also there is not the specific drug of above-mentioned disease basically.
For obstinate diseases such as infection by Treponema pallidum, tinea unguium, fungus and antibacterial MOI, how to find the recurrence problem after its treatment is thoroughly effected a radical cure and solved to effective medical procedure, become the medical circle task of top priority now.
Summary of the invention
Based on present treatment present situation for infectious disease, the inventor has carried out groping widely and screening to antimicrobial drug, antifungal agent and antibacterium medicine are carried out effectively composite, in treatment infection by Treponema pallidum, tinea unguium, beriberi, fungus and antibacterial MOI disease, obtained beyond thought effect.
So the present invention at first provides a kind of anti-infective medicament composition, extensive more and effective antimicrobial high-efficiency antimicrobial medicine can be used for treating infection by Treponema pallidum, tinea unguium, beriberi and MOI disease as a kind of subject range.
" the MOI disease " that reaches of the present invention is meant at the serious skin infection of clinical manifestation, disclose its infectious bacteria at least at two or more through antibacterial culturing, use existing broad spectrum antibiotic and antifungal or anti-bacterial drug is invalid substantially or DeGrain targetedly.
Anti-infective medicament composition of the present invention is composited by present known antifungal component and antibacterium component, and described antibacterial components can be one or more combination, particularly, wherein contains bifonazole and hibitane at least.The weight ratio of bifonazole and hibitane is 20 in the said composition: 1-1: 2, and preferred weight ratio is 2: 1-1: 2, more preferably about 1: 1.
Pharmaceutical composition of the present invention is by the synergism of described antifungal component and antibacterium component, can improve the antibacterial therapy effect, thereby solved that traditional antimicrobial drug therapeutic domain is narrow, treatment thoroughly and easy shortcoming such as recurrence, become novel high-efficiency antimicrobial medicine.
Except that containing above-mentioned antibacterial components, also alternatively comprise the antibacterial components that is selected from amoxicillin, chlortetracycline, econazole, ketoconazole, clotrimazole, miconazole and the peracetic acid etc. one or more in the said composition, and the pharmacy acceptable auxiliary.
The preferred pharmaceutical composition according to the present invention, with 100 parts be benchmark, the weight ratio of each component is bifonazole 0.1-10 part, hibitane 0.1-10 part, all the other each component drug are respectively 0.1-10 part, all the other are pharmacy acceptable auxiliary and water.To those skilled in the art, optionally composite these antibacterial components can make up the medicine series compositions at various infectious disease.
Therefore, the present invention also provides a kind of anti-infective medicament composition, comprising weight ratio is 20: 1-1: 2 bifonazole and hibitane, also comprise the drug component that is selected from amoxicillin, chlortetracycline, econazole, ketoconazole, clotrimazole, miconazole and the peracetic acid one or more, with 100 weight portions is benchmark, said composition consist of bifonazole 0.1-10 part, hibitane 0.1-10 part, all the other each drug components are respectively 0.1-10 part, also comprise pharmacy acceptable auxiliary 70-99.7 part.
Pharmaceutical composition of the present invention can comprise dosage forms such as ointment, suppository, liniment, lotion, membrane, patch, aerosol.The same with other external used medicines, the excipient substance that the present invention uses should satisfy the requirement of preparation medicine for external use.For example, use excipient substances such as white paraffin, fatty glyceride through oil-in-water or water in oil emulsifying process, oil phase and water are mixed fully, it is even, fine and smooth to obtain medicine, has the ointment of certain toughness; Perhaps use fatty glyceride, Myrj 45 etc. to make suppository; Or adopt drug solns and suitable propellant to make aerosol.Can obtain dosage forms such as liniment, solution, cream again by the prescription composition.Above-mentioned adjuvant all belongs to pharmaceutical adjuvant commonly used, and the present invention does not have specific (special) requirements to it.
In clinical treatment, according to concrete disease, the directly medication for several times in a day in the affected part is eliminated up to disease.Compositions of the present invention can be used separately or also use with other antibacterials.
The various antibacterial components that the present composition comprises can directly be selected the crude drug of suitability for industrialized production for use, by the synergism of each component, more can bring into play the peculiar curative effect of each antimicrobial drug to greatest extent.As a kind of compound medicines, clinical test results shows that bactericidal composition of the present invention obviously is better than single medicine component therapeutic effect of antibacterials commonly used at present for the antibacterial effect of the various sources of infection.
So, the present invention also aims to provide the external used medicine dosage form of utilizing this pharmaceutical composition to make, comprise ointment, liniment, solution, cream, suppository and aerosol etc., be used for the treatment of intractable skin infection diseases such as fungus and antibacterial MOI and infection by Treponema pallidum, tinea unguium, beriberi, solved that traditional antimicrobial drug therapeutic domain is narrow, a treatment thoroughly and easy difficult problem such as recurrence, improve curative effect antibiotic and the treatment MOI, filled up the blank of no active drug in this class disease treatment.
The present invention also provides the preparation method of aforementioned pharmaceutical compositions external preparation, comprise substrate heat fused, water and the oil phase of ointment mixing, emulsifying, ingredient dissolving and with substrate in mixing; The substrate heat fused of suppository, ingredient emulsifying or be suspended in the substrate, go into the mould and the demoulding etc.
For example, the emulsifiable paste that makes of pharmaceutical composition according to the present invention adopts oil-in-water or water in oil processing technology emulsifying to process.Said preparation is the milky paste, and wherein drug content is generally at 0.1-10%, special aroma flavor slightly, and pH5～6, water-soluble, methanol and ethanol, all very stable to light and heat, can directly be applied to skin.Stability test proves that this ointment product at room temperature can be preserved more than 2 years.
Said method is the routine operation of topical agent, and is different with selected adjuvant according to concrete compatibility of drugs, and required equipment and technological process are than routine operation also difference to some extent, and described these all belong to techniques well known, repeat no more.
Pharmacodynamic experiment
The sample that uses in the experiment is composite dose of bifonazole and hibitane crude drug, ratio is 1: 1, bifonazole is produced by Wuxi Dong Dan auxiliary reagent factory, hibitane is produced by Jinzhou nine safe pharmaceutcal corporation, Ltds, and adds white vaseline, liquid paraffin, glycerol and stearic acid etc. and make ointment (code name WF represents).
1, extracorporeal bacteria inhibitor test
1.1 materials and methods
1.1.1 trial drug: WF.
1.1.2 test strain: totally 61 strains are provided by Nanjing institute of internal medicine of the Chinese Academy of Medical Sciences, fungal studies center, BJ Medical University 1st Subsidiary Hospital.Wherein: Candida albicans 34 strains, Oidium tropicale 9 strains, candida krusei 3 strains, monilia guilliermondii 3 strains, Candida parapsilosis 7 strains, Candida glabrata 1 strain, staphylococcus aureus 3 strains, trichophyton 1 strain.
1.1.3 culture medium: Sabouraud's dextrose agar (SDA): glucose 40g, peptone 10g, agar 15g, distilled water 1000ml are used for the activation of strain; Improvement Sha Shi Glucose Liquid base (SDB): glucose 20g, new peptone 10g, distilled water 1000ml are used to measure the MIC scope of strain.
1.1.4 the preparation of culture medium: take by weighing all compositions by culture medium prescription, 15 pounds of sterilizations in 15 minutes.
1.1.5 medicine is preserved the preparation of liquid: the WF solution of preparation 640ug/ml concentration, preserve liquid as medicine ,-20 ℃ of preservations are standby.
1.1.6 the preparation of pharmaceutical culture medium: the thing of getting it filled is preserved the pharmaceutical culture medium that liquid 0.5ml and Sha Shi Glucose Liquid basigamy are made 16ug/ml concentration, gets the pharmaceutical culture medium of 6 concentration through doubling dilution, and concentration is respectively 8,4,2,1,0.5 and 0.25ug/ml, bifonazole concentration is 8,4,2,1,0.5 and 0.25ug/ml, hibitane concentration is 8,4,2,1,0.5 and 0.25ug/ml, and do not contain the blank culture medium of medicine, the packing test tube, every pipe 1ml, 15 pounds of sterilizations in 15 minutes, standby.
1.1.7 inoculation bacterium liquid: every strain bacterium is adopted the two generations activation of SDA culture medium culturing, and the second filial generation is cultivated in 24 hours and got 5 single bacterium colonies in 0.85% physiological saline solution, shakes to form the bacterium suspension 15 seconds, and counting is regulated and is mixed with concentration is 0.5% * 10
5～2.5 * 10
5The cfu/ml bacteria suspension, standby.
1.1.8 efficacy evaluation: with the bacterium liquid inoculation pharmaceutical culture medium for preparing, every pipe inoculation 20ul, two groups in the parallel work of every strain bacterium is cultivated 24～48 hours observed results for 35 ℃.Observe the bacterial growth situation every day, calculate the MIC scope when experiment finishes.
1.2 result: this test adopts improvement Sha Shi liquid base method to measure the MIC scope of WF to Candida part fungus.
The results are shown in Table 1.
By table 1 as seen: contain the WF culture medium and compare with blank culture medium, WF to Candida albicans, staphylococcus aureus and and MOI good fungistatic effect is all arranged, its minimum inhibitory concentration (MIC) and singly only has bacteriostasis to antibacterial or fungus with bifonazole and hibitane all below 4ug/ml.
Table 1, WF extracorporeal bacteria inhibitor test result
| Strain | Bacterial strain number (ug/ml) | WF (ug/ml) | Bifonazole (ug/ml) | Hibitane (ug/ml) | Blank culture medium |
| Candida albicans Candida tropicalis Candida parapsilosis candida krusei monilia guilliermondii Candida glabrata Trichophyton rubrum staphylococcus aureus staphylococcus aureus+Candida albicans staphylococcus aureus+Trichophyton rubrum | 34 9 7 3 3 1 1 3 1 1 1 1 | 0.5-1 0.5-1 1-2 1-2 2-4 0.5-1 0.5-1 0.5-1 0.5-1 0.5-1 | 2-4 2-4 2-4 4-8 4-8 2-4 2-4 + + + | + + + + + + + 2-4 + + | + + + + + + + + + + |
Annotate :+expression antibacterial normal growth
2, to the therapeutical effect of animal skin MOI
2.1 materials and methods
2.1.1 animal: Cavia porcellus, male, 40, body weight 160-200 gram.
2.1.2 experiment grouping: be divided into 4 groups at random by animal body is heavy: the WF group, bifonazole group and hibitane group, bifonazole ointment (being produced by Fourth Ring the pharmaceutical factory)+2% hibitane cleaning solution (purchasing in market) that contains biphenyl Bian azoles 1.0% is organized.Animal is handled two skin depilatories in back.
2.1.3 animal model is set up: two skin infections of back part of animal use trichophyton gypseum and golden yellow Fructus Vitis viniferae ball concurrent infection to form typical MOI dermatitis after 5 days.
2.1.4 medicine and medication: WF group drug level is 1.0%, bifonazole group 1.0%, hibitane group 1.0%, the drug combination group is an amount of and 2% hibitane cleaning solution group coupling of 1.0% bifonazole ointment, after MOI forms, every day is smeared medication 2 times in two skin infection districts of back part of animal, 4 weeks of the course of treatment.
2.1.5 efficacy determination: divide effectively and invalid secondary.
Effectively: skin lesion disappears substantially, and is local red, swollen, bitterly, squama, dipping, blister, oozes out symptom such as skin itching and disappears substantially, and fungus, bacterioscopy or fungus antibacterial culturing are negative.Invalid: skin lesion changes little or increases the weight of, and is local red, swollen, bitterly, squama, dipping, blister, oozes out doing well,improving such as skin itching not quite or increase the weight of, and fungus bacterioscopy or fungus antibacterial culturing are positive.
2.1.6 clinical observation: animal is observed 2 times every day.According to the skin damage situation, as red, swollen, bitterly, squama, dipping, blister, ooze out skin itching and be divided into 5 grades: 1=does not have, and 2=is light, and among the 3=, 4=is heavy, and 5=is heavy.According to clinical symptoms, rating gives clinical evaluation weekly, is effective below 2 grades.Make the fungus bacterioscopy, the course of treatment, end was made the fungus antibacterial culturing once at every turn.
2.7 therapeutic effect
In 10 animals of WF ointment treatment group, in treatment the 14th day the time 6 do not had scurf, red, swollen, squama, dipping, blister, the degree of oozing out obviously alleviate, the tinea of other animal also is clearly better.Treat after 30 days, all animal scurfs all disappear, and grow virgin wool.Bifonazole ointment and the treatment of hibitane cleaning solution logotype group 14 days, 1 animal clinical symptoms takes a turn for the better, and treatment has 3 animal clinical symptoms to take a turn for the better when finishing; Single with the commentaries on classics of not getting better of 1.0% group of 1.0% group of bifonazole and hibitane animal skin inflammation in the identical time.
The result shows that WF Ointment in Treatment effect is better than bifonazole ointment and hibitane cleaning solution coupling group and single with bifonazole and hibitane group.
3, anti-infection by Treponema pallidum effect
3.1 kill treponema pallidum virulent strain experiment 1
3.1.1 animal: new zealand rabbit, female, 60,3-3.5Kg.
3.1.2 the animal grouping: animal is divided into three groups at random according to body weight, WF group, matched group, penicillin positive controls.Every group 20
3.1.3 medicine: 1.0%WF, 10,000 units/ml penicillin.
3.1.4 bacterial strain: treponema pallidum Nichols strain.
3.1.5 bacterium liquid preparation and inoculation: 0.2ml 1.0%WF and 0.2ml1 ten thousand units/ml penicillin respectively with certain dense change treponema pallidum effect after 2-4 minute, be seeded to the new zealand rabbit bilateral testes, the treponema pallidum of matched group direct inoculation same concentrations.
3.1.6 clinical observation: in experiment periods 1 month, observe symptom sickness rate such as animal bilateral testes ulcer, adopt round pcr to detect, and positive rate of relatively respectively organizing.
3.1.7 therapeutic effect
Symptoms such as bilateral testes ulcer, sickness rate 100%, the antibody test positive 100% all appear in 20 animals of the matched group of not administration; WF treatment group does not have the animal morbidity, and antibody test is all negative; Penicillin group 20 16 animals morbidity of having merely hit, the antibody test positive rate is 80%.
Illustrate that WF compares the stronger treponema pallidum virulent strain effect of killing with penicillin.(, therefore do not see experiment and research report that the medicine antibacterial effect is arranged so far as yet because treponema pallidum artificial culture problem does not solve so far fully for many years.The positive control drug of this research can only be selected the penicillin medicine that leptospira is had certain effect for use.)
3.2 kill treponema pallidum virulent strain experiment 2
3.2.1 animal: new zealand rabbit, female, 60,3-3.5Kg.
3.2.2 the animal grouping: animal is divided into three groups at random according to body weight: WF group, matched group, penicillin positive controls.Every group 20.
3.2.3 medicine: 1.0%WF, 10,000 units/ml penicillin.
3.2.4 bacterial strain: treponema pallidum Nichols strain.
3.2.5 preparation of bacterium liquid and inoculation: 0.2m1 1.0%WF and the effect of finite concentration treponema pallidum were seeded to the new zealand rabbit bilateral testes after 2-4 minute.
3.2.6 clinical observation: in experiment periods 1 month, observe symptom sickness rate such as animal bilateral testes ulcer, adopt round pcr to detect, and positive rate of relatively respectively organizing.
3.2.7 therapeutic effect
Symptoms such as bilateral testes ulcer, sickness rate 100%, the antibody test positive 100% all appear in 20 animals of the matched group of not administration; WF treatment group does not have the animal morbidity, and antibody test is all negative; Penicillin group 12 animals of having merely hit through penicillin injection treatment back 20 fall ill, and the antibody test positive rate is 60%.More than explanation WF has the stronger treponema pallidum virulent strain effect of killing, and penicillin also has certain anti-treponema pallidum virulent strain effect.
4, to superficial skin fungus and antibacterial MOI patient's therapeutic effect
4.1 materials and methods
4.1.1 case is selected: clinical definite is superficial skin fungus and bacterial disease (comprising tinea corporis, tinea cruris etc.), through fungus microscope examination and antibacterial and fungal culture prover.
4.1.2 the grouping of clinic trial case: 100 examples are divided into 3 groups: WF organizes each 30 example of 40 examples, bifonazole group and hibitane group.
4.1.3 the Therapeutic Method and the course of treatment: be applied to the affected part with an amount of emulsifiable paste, one day secondary, 4 weeks of the course of treatment.
4.1.4 efficacy determination: divide effectively and invalid secondary.Effectively: skin lesion disappears substantially, and is local red, swollen, bitterly, squama, dipping, blister, oozes out transference cure such as skin itching, and fungus, bacterioscopy or fungus antibacterial culturing are negative.Invalid: skin lesion changes little or increases the weight of, and is local red, swollen, bitterly, squama, dipping, blister, oozes out doing well,improving such as skin itching not quite or increase the weight of fungus bacterioscopy or fungus positive bacterial culture.
4.1.5 clinical observation: observe every day 2 times.According to the skin damage situation, as red, swollen, bitterly, squama, dipping, blister, ooze out skin itching and be divided into 5 grades: 1=does not have, and 2=is light, and among the 3=, 4=is heavy, and 5=is heavy.Observe once weekly, according to clinical symptoms, rating gives clinical evaluation, for effective (comprising 2 grades), makes the fungus bacterioscopy below 2 grades at every turn, and the course of treatment, end was made the fungus antibacterial culturing once.
4.2 therapeutic effect: effective 48 examples are organized in the WF treatment, account for 96%, and invalid 2 examples account for 4%.Effective 3 examples of bifonazole account for 10%, and invalid 27 examples account for 90%, and effective 2 examples of hibitane group account for 6.7%, and invalid 28 examples account for 93.3%.WF group and bifonazole and hibitane group be significant difference relatively.Prompting WF has obvious therapeutic action to superficial skin fungus and antibacterial MOI.
5, to clinical tinea unguium patient's therapeutic effect
5.1 materials and methods
5.1.1 case is selected: make a definite diagnosis nail fungi clinically and infect (tinea unguium), and enter test through fungal culture prover 150 examples.
5.1.2 the grouping of clinic trial case: 150 examples are divided into 3 groups: WF group, bifonazole group and hibitane group.Every group 50 case.
5.1.3 the Therapeutic Method and the course of treatment: be applied to the affected part with an amount of emulsifiable paste, one day secondary, 4 weeks of the course of treatment.
5.1.4 efficacy determination: divide effectively and invalid secondary.Effectively: grow new normal nail; Invalid: fingernail is grey black and thickens, the commentaries on classics of not getting better of squama hypertrophy pathological changes.
5.2 therapeutic outcome
Effective 45 examples of WF account for 90%, and invalid 5 examples account for 10%; Effective 5 examples of bifonazole group account for 10%, and invalid 45 examples account for 90%; Effective 2 examples of hibitane group account for 4%, and invalid 48 examples account for 96%, and the WF group compares significant difference with bifonazole group and hibitane group.Point out product WF of the present invention that tinea unguium is had the good curing effect.
6, drug toxicity
Product of the present invention shows to the acute toxicity of mice with to the experimental result of the long term toxicity of rat, the about 10.0g/kg of mouse stomach maximum tolerated dose, and fail to measure LD
50Rat is carried out continuous 3 months 5,15 and 30 times of percutaneous drug deliveries with the clinical application amount, and animal does not see any side reaction.
Conclusion:
The principles of formulating prescriptions of the present composition are to adopt medicine 5 usefulness of one or more treatment funguses and one or more treatment bacterial infections, and pharmacodynamic study is found the MOI patient is produced beyond thought therapeutic effect.Find that simultaneously the present composition can kill treponema pallidum, tinea unguium is also had excellent curative.Its Study on mechanism shows that the present invention has stronger killing action to fungus, antibacterial and treponema pallidum virulent strain.
In a word, the present composition has following characteristics as the medicine of anti-infection by Treponema pallidum, tinea unguium, fungus and antibacterial MOI: (1) anti-infection by Treponema pallidum, the effect of treatment tinea unguium, filled up the blank that in the clinical treatment above two kinds of diseases is lacked active drug.(2) find that first said composition has good therapeutic effect simultaneously to fungus and antibacterial MOI, and after repeatedly treating, can reach thorough therapeutic purposes.(3) toxic and side effects is little, and is easy to use, but life-time service.
Compositions of the present invention is compared with traditional antimicrobial drug, overcome that therapeutic domain is narrow, treatment thoroughly and easy shortcoming such as recurrence, and improve antibiotic and treatment MOI curative effect, the advantage that the present invention does not simultaneously have use crowd's restriction has overcome the suitable limited defective of crowd of antagonism treponema pallidum virulent strain aspect penicillin again, therefore, product of the present invention is captured above disease and will be produced active influence to multiple disease treatment the mankind.
The specific embodiment
Further set forth the present invention below in conjunction with embodiment, but not as limiting the scope of the invention.Antibacterial components related among the embodiment is all from the pharmaceutical grade crude drug that is purchased.
Embodiment 1:
1 part of bifonazole, 1 part of hibitane, 20 parts of liquid paraffin, 5 parts of stearic acid, 10 parts of fatty glycerides, water add to 100 parts.
Said components adopts oil-in-water emulsifying process, and is fully emulsified through stirring, and is prepared into ointment, this ointment medicine evenly, fine and smooth, have suitable toughness, non-stimulated to skin.
Above-mentioned ointment removes the treatment that can be used for above-mentioned disease (compound skin infection and tinea unguium), also in outpatient service, be provided for the vitamin B1 deficiency patient of obstinate and repeated infection, secondary spread on the affected part outward in one day, according to the difference of gradient of infection, all can achieve good results after two weeks.
Embodiment 2:
2 parts of amoxicillin, 1 part of bifonazole, 5 parts of ketoconazoles, 2 parts in chlortetracycline, 3 parts of clotrimazoles, 5 parts of miconazoles, 0.1 part of hibitane, 0.1 part of peracetic acid, 30 parts of fatty glycerides, 5 parts of Myrj 45s, 5 parts of cocoa butters, 2 parts of hydrogenated vegetable oils, water add to 100 parts.
With medicine and substrate mix homogeneously,, make difform suppository according to the difference of using tract.
Embodiment 3:
2 parts of bifonazoles, 3 parts of ketoconazoles, 0.1 part of clotrimazole; 1 part of hibitane; 0.1 part of peracetic acid, 30 parts in adjuvant white paraffin, 3 parts of fatty glycerides, water add to 100 parts.
Adopt oil-in-water emulsifying process, it is fully emulsified to stir, and is prepared into ointment.
More than described the preferred embodiment for the present invention, so it is not in order to limit the present invention.Those skilled in the art can not depart from the improvement and the variation of category of the present invention and spirit to embodiment disclosed herein.
Claims (6)
1, a kind of anti-infective medicament composition, comprising weight ratio is 20: 1-1: 2 bifonazole and hibitane are benchmark with 100 weight portions, said composition consist of bifonazole 0.1-10 part, hibitane 0.1-10 part, pharmacy acceptable auxiliary 80-99.8 part.
2, a kind of anti-infective medicament composition, comprising weight ratio is 20: 1-1: 2 bifonazole and hibitane, also comprise the drug component that is selected from amoxicillin, chlortetracycline, econazole, ketoconazole, clotrimazole, miconazole and the peracetic acid one or more, with 100 weight portions is benchmark, said composition consist of bifonazole 0.1-10 part, hibitane 0.1-10 part, all the other each drug components are respectively 0.1-10 part, also comprise pharmacy acceptable auxiliary 70-99.7 part.
3, pharmaceutical composition as claimed in claim 1 or 2, wherein, the weight ratio of bifonazole and hibitane is 2: 1-1: 2.
4, pharmaceutical composition as claimed in claim 1 or 2 is characterized in that described compositions is an externally-applied medicinal composition.
5, as pharmaceutical composition as described in the claim 4, wherein, described external used medicine dosage form comprises ointment, suppository, liniment, cream, lotion, membrane, patch and aerosol.
6, claim 1 or the 2 described anti-infective medicament compositions application in the medicine of preparation treatment infection by Treponema pallidum, tinea unguium or fungus and antibacterial MOI.
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