CN1552314A - Antibacterial medicinal composition - Google Patents
Antibacterial medicinal composition Download PDFInfo
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- CN1552314A CN1552314A CNA031405193A CN03140519A CN1552314A CN 1552314 A CN1552314 A CN 1552314A CN A031405193 A CNA031405193 A CN A031405193A CN 03140519 A CN03140519 A CN 03140519A CN 1552314 A CN1552314 A CN 1552314A
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- CN
- China
- Prior art keywords
- antibacterial
- disinfectant
- fluconazol
- chlorhexidine
- medicament
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 53
- 239000000203 mixture Substances 0.000 title description 33
- 239000003814 drug Substances 0.000 claims abstract description 54
- 229960002152 chlorhexidine acetate Drugs 0.000 claims abstract description 31
- MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 claims abstract description 31
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 claims abstract description 31
- 229960002722 terbinafine Drugs 0.000 claims abstract description 31
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000000645 desinfectant Substances 0.000 claims abstract description 24
- 210000004877 mucosa Anatomy 0.000 claims abstract description 8
- 239000002674 ointment Substances 0.000 claims description 16
- OLUNPKFOFGZHRT-YGCVIUNWSA-N Naftifine hydrochloride Chemical compound Cl.C=1C=CC2=CC=CC=C2C=1CN(C)C\C=C\C1=CC=CC=C1 OLUNPKFOFGZHRT-YGCVIUNWSA-N 0.000 claims description 15
- 229960003979 naftifine hydrochloride Drugs 0.000 claims description 15
- 230000001954 sterilising effect Effects 0.000 claims description 14
- 238000004659 sterilization and disinfection Methods 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 13
- 238000005303 weighing Methods 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000002552 dosage form Substances 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 239000007921 spray Substances 0.000 claims description 6
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- 239000000843 powder Substances 0.000 claims description 4
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- -1 tincture Substances 0.000 claims description 4
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- 239000002398 materia medica Substances 0.000 claims description 2
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- 230000000694 effects Effects 0.000 abstract description 24
- 229960004313 naftifine Drugs 0.000 abstract description 15
- OZGNYLLQHRPOBR-DHZHZOJOSA-N naftifine Chemical compound C=1C=CC2=CC=CC=C2C=1CN(C)C\C=C\C1=CC=CC=C1 OZGNYLLQHRPOBR-DHZHZOJOSA-N 0.000 abstract description 15
- 208000015181 infectious disease Diseases 0.000 abstract description 4
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- 229960004884 fluconazole Drugs 0.000 abstract description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 27
- 229960003260 chlorhexidine Drugs 0.000 description 27
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 241000222122 Candida albicans Species 0.000 description 13
- 229940088710 antibiotic agent Drugs 0.000 description 13
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- 230000003211 malignant effect Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 241000191967 Staphylococcus aureus Species 0.000 description 10
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- 230000002401 inhibitory effect Effects 0.000 description 9
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical group CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 8
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- 238000002474 experimental method Methods 0.000 description 5
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
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- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
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- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
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- 241001480043 Arthrodermataceae Species 0.000 description 1
- 206010005913 Body tinea Diseases 0.000 description 1
- 235000007516 Chrysanthemum Nutrition 0.000 description 1
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
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- 230000037304 dermatophytes Effects 0.000 description 1
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
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- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
An antibacterial composite medicine for skin and mucosa contains chlorhexidine acetate and terbinafine (or naftifine) hydrochloride or fluconazole. It can be used as exterio-applied medicine or disinfectant for prepenting and treating fungus and/or bacterium infection to skin and mucosa without high curative effect and low toxic by-effect.
Description
Technical field
The present invention relates to a kind of antibacterial combination, relate in particular to a kind of skin and mucosa antibacterials compound recipe chlorhexidine acetate compositions.
Background technology
Chlorhexidine acetate (the former name chlorhexidine acetate is called for short chlorhexidine, Chlorhexidine) be anti-bacterial drug, but to treatment with prevent skin, mucosa fungal infection or fungus, the two mixed infection effect of antibacterial undesirable; Terbinafine HCl (is called for short terbinafine, Terbinafine), naftifine hydrochloride (is called for short naftifine, Naftifine), fluconazol (Fluconazole) is an antifungal drug, it is characterized in that the higher mycostasis that kills is arranged, cure rate is higher and relapse rate is lower in a short time, but to the patient of some dermatomycosis or fungus, the two mixed infection of antibacterial, curative effect is not ideal enough.Existing market demand is a kind of to be had the medicine of better effects and can also be used for external sterilization medicine skin and mucosa fungal infection or fungus, the two mixed infection of antibacterial.
Summary of the invention
The purpose of this invention is to provide a kind of antibacterial combination, a kind of skin and mucosa antibacterials compound recipe chlorhexidine acetate compositions especially are provided, have overcome above-mentioned one-component and can not effectively treat the disease that cutaneous fungal infection or fungus, the two mixed infection of antibacterial causes and the shortcoming of external sterilization thereof.
The present invention is achieved through the following technical solutions:
A kind of antibacterial combination comprises chlorhexidine acetate, terbinafine HCl or naftifine hydrochloride or fluconazol;
A kind of antibacterial combination is by the medicament that comprises that following proportioning ratio component is made, and chlorhexidine acetate: terbinafine HCl or naftifine hydrochloride or fluconazol are 0.1～2.0: 0.3～3.0; Be preferably 0.3～1.0: 0.5～2.0; Especially for being 0.5: 1.0.
Described medicament can also comprise available adjuvant on the materia medica;
Described medicament can be said skin on any pharmaceutics and mucosa delivery dosage form; Especially can be ointment, ointment, solution, tincture, suppository, spray;
Described medicament can also be said disinfectant on any pharmaceutics; Especially can be liquid disinfectant, disinfected paper napkin, sterilization fabric, disinfectant tablet and disinfectant powder.
The preparation method of described antibacterial combination may further comprise the steps:
Take by weighing chlorhexidine acetate, terbinafine HCl or naftifine hydrochloride or fluconazol in described ratio, the preparation method of complying with conventional dermatologic and disinfectant is prepared from;
Described preparation method also comprises any pharmaceutically available adjuvant of adding.
The present invention has following effect and advantage:
1) medicine of the present invention has synergism and potentiation to antifungal.Utilize two kinds of drug component effects separately, make up the back and find that composition medicine has synergism aspect antifungal, and it is unaffected to have kept its antibacterium effect.
2) can be used for developing new compound external-use local application and disinfectant, as compositions ointment, solution and disinfectant etc., the patient who clinically some cutaneous fungal infection is merged bacterial infection, unique curative effect and disinfective action are arranged, also do not influence simple fungus or bacterial infection treating for skin disease effect and remove pathogen.Clinical principium test above-mentioned composition ointment, treatment numerical example dermatophytes or antibacterial, or the patient of fungus and the two infection mixed infection of antibacterial, and be used for people's hands, sufficient sterilization and gynecological's sterilization, all obtain the curative effect of satisfaction.
Described advantage of the present invention and effect can illustrate by following experiment.
One, following experiment can illustrate the synergism and the potentiation of pharmaceutical composition of the present invention
1. experiment in vitro---the external antibacterial action to several frequently seen pathomycete and part antibacterial (representing bacterium) of pharmaceutical composition of the present invention and component thereof compares, purpose is that each set of dispense of compositions that filters out mycostasis compares ratio, by measuring its minimal inhibitory concentration (MIC), prove the bacteriostasis to fungus of the present invention, reach killing action fungus and antibacterial.
1.1 materials and methods
1.1.1 strain
Fungus is drawn from the air force general hospital department of dermatologry, and antibacterial is drawn from preventive medicine academy of science institute of Antibiotics and air force general hospital clinical laboratory.
1.1.2 culture medium
Fungi culture medium is the Sha Shi broth bouillon, and by mainly being made up of 1% peptone and 2% glucose, PH is 6-6.5; Bacteria culture media is an ordinary broth, and PH is 7.
1.1.3 the preparation of medicinal liquid culture medium
In chlorhexidine acetate and terbinafine HCl or naftifine hydrochloride or the different ratio preparation of fluconazol.
Each composite formula with 1ml 95% dissolve with ethanol, adds sterile distilled water to 5ml earlier again; Respectively draw above-mentioned dosing 0.2ml then, be added to respectively in the culture medium of 1.8ml, shake up the medicinal liquid culture medium that the back two-fold dilution goes out variable concentrations.During experiment, add bacterium liquid 0.02ml among every pipe medicinal liquid culture medium 1ml; 1ml contains trichophyton 10
5-10
6Individual or yeast-like fungi 10
3-10
4Individual.Be put in after shaking up in 28 ℃ of incubators and cultivated 120-168 hour, wherein yeast-like fungi is 48 hours, observed result.
1.1.4 drug effect criterion
The limpid medicine blank pipe that is same as of meat soup is for there being the bactericidal action of pressing down; Meat soup is obviously muddy, or the Mycoderma growth is arranged, then for there not being the bactericidal action of pressing down.
1.1.5 the mensuration of bacteriocidal concentration
This method is used the agar tilt-pour process.Earlier pharmaceutical composition of the present invention is made into and contains variable concentrations medicinal liquid culture medium, 0.01 μ g/ml-100 μ g/ml; Every again ml adds the test bacterium respectively, and the bacterium amount acts on after several minutes for 103-106 (ml), is preferably 5 minutes, and the 0.1ml that takes a sample respectively is inoculated in plate, pours sabouraud's agar into, fully shakes up, and cultivates 5-10 days; Count plate and statistical result.
1.2 experimental result
1.2.1 the external effect of compositions and component thereof to the common pathomycete of 4 strains (representing bacterium)
Compositions and its component chlorhexidine, terbinafine or naftifine or fluconazol comparison shows that to the common pathomycete of 4 strains (representing bacterium) bacteriostatic test, chlorhexidine and terbinafine or naftifine or fluconazol are in (0.3～1.0): (0.5～2.0) weight portion proportioning ratio compositions formulated is lower to the minimal inhibitory concentration (MIC) of several frequently seen pathomycete, effect strong (see Table 1, table 2, table 3), the proof compositions is better than its one pack system medicine, and antifungal has synergism.
1.2.2 the external effect of compositions and component thereof to the common malignant bacteria of 4 strains (representing bacterium)
Compositions and its component chlorhexidine, terbinafine or naftifine or fluconazol comparison shows that to the common malignant bacteria of 4 strains (representing bacterium) bacteriostatic test, chlorhexidine and terbinafine or naftifine or fluconazol are in (0.3～1.0): the minimal inhibitory concentration (MIC) to several frequently seen pathomycete during (0.5～2.0) weight portion proportioning ratio is also lower, effect strong (see Table 4, table 5, table 6).Behind proof chlorhexidine and terbinafine or naftifine or the fluconazol compatibility, the effect of chlorhexidine inhibition antibacterial is unaffected.
1.2.3 compositions and component thereof are to the bactericidal action of common malignant bacteria of 3 strains and fungus (representing bacterium)
Measure the bactericidal action of compositions and component thereof to common malignant bacteria of 3 strains and fungus, the result shows, chlorhexidine and terbinafine, naftifine or fluconazol are in (0.3～1.0): (0.5～2.0) weight portion proportioning ratio preparation group has bactericidal action preferably (see Table 7, table 8, table 9), two strain malignant bacterias are represented bacterium staphylococcus aureus and escherichia coli, composition effect is not less than its component, still has kill bacteria effect preferably; Fungus is represented the bacterium Candida albicans, and compositions is better than its component, and killing fungus has synergism.
The external bacteriostasis of table 1 chlorhexidine and terbinafine variable concentrations compatibility to several frequently seen pathomycete (representing bacterium)
Minimal inhibitory concentration (MIC, μ g/ml)
Chlorhexidine: terbinafine
Trichophyton alpha fungus Sabouraudites lanosus Candida albicans
0.05∶0.2 0.0128 0.0258 0.0128 5.00
0.1∶0.2 0.0064 0.0128 0.0064 2.50
0.3∶0.5 0.0016 0.0032 0.0016 1.25
0.3∶1.0 0.0016 0.0032 0.0016 0.62
0.3∶2.0 0.0008 0.0016 0.0008 0.62
0.3∶3.0 --- --- --- ---
0.5∶0.2 0.0064 0.0064 0.0032 2.50
0.5∶0.5 0.0016 0.0032 0.0016 1.25
0.5∶1.0 0.0004 0.0008 0.0008 0.31
0.5∶2.0 0.0004 0.0008 0.0004 0.31
0.5∶3.0 --- --- --- ---
1.0∶0.2 0.0064 0.0064 0.0064 1.25
1.0∶0.3 0.0016 0.0032 0.0032 1.25
1.0∶1.0 0.0008 0.0008 0.0008 0.62
1.0∶2.0 0.0008 0.0008 0.0004 0.62
1.0∶2.5 --- --- --- ---
2.0∶0.5 --- --- --- ---
1.0: 0.0 (single medicine contrast) 1.250 0.625 0.625 2.50
0.0: 1.0 (single medicine contrasts) 0.0032 0.012 0.012 1.25
Annotate: 1. trichophyton was cultivated 120-168 hour, and Candida albicans is cultivated 48 hours observed results.
2. the high dissolving of "---" drug level is bad, can't observed result.
The external bacteriostasis of table 2 chlorhexidine and naftifine variable concentrations compatibility to several frequently seen pathomycete (representing bacterium)
Minimal inhibitory concentration (MIC, μ g/ml)
Chlorhexidine: naftifine
Trichophyton alpha fungus Sabouraudites lanosus Candida albicans
0.05∶0.2 0.096 0.096 0.182 10.00
0.1∶0.2 0.048 0.048 0.064 5.00
0.3∶0.5 0.012 0.012 0.012 2.50
0.3∶1.0 0.012 0.012 0.012 1.25
0.3∶2.0 0.006 0.012 0.006 1.25
0.3∶3.0 --- --- --- ---
0.5∶0.2 0.048 0.048 0.048 2.50
0.5∶0.5 0.012 0.024 0.024 2.50
0.5∶1.0 0.003 0.003 0.003 1.25
0.5∶2.0 0.006 0.003 0.003 0.62
0.5∶3.0 --- --- --- ---
1.0∶0.2 0.024 0.024 0.048 2.50
1.0∶0.3 0.012 0.012 0.048 1.25
1.0∶1.0 0.003 0.003 0.006 1.25
1.0∶2.0 0.003 0.003 0.006 1.25
1.0∶2.5 --- --- --- ---
2.0∶0.5 --- --- --- ---
1.0: 0.0 (single medicine contrast) 1.250 0.625 0.625 2.50
0.0: 1.0 (single medicine contrasts) 0.024 0.012 0.048 2.50
Annotate: 1. trichophyton was cultivated 120-168 hour, and Candida albicans is cultivated 48 hours observed results.
2. the high dissolving of "---" drug level is bad, can't observed result.
The external bacteriostasis of table 3 chlorhexidine and fluconazol variable concentrations compatibility to several frequently seen pathomycete (representing bacterium)
Minimal inhibitory concentration (MIC, μ g/ml)
Chlorhexidine: fluconazol
Trichophyton alpha fungus Sabouraudites lanosus Candida albicans
0.05∶0.2 5.00 5.00 10.00 5.00
0.1∶0.2 2.50 5.00 5.00 5.00
0.3∶0.5 0.625 1.25 2.50 1.25
0.3∶1.0 0.625 1.25 1.25 1.25
0.3∶2.0 0.625 1.25 1.25 0.625
0.3∶3.0 --- --- --- ---
0.5∶0.2 1.25 2.50 2.50 2.50
0.5∶0.5 0.312 0.625 1.25 2.50
0.5∶1.0 0.156 0.312 0.312 0.625
0.5∶2.0 0.156 0.156 0.312 0.625
0.5∶3.0 --- --- --- ---
1.0∶0.2 0.312 0.312 0.625 2.50
1.0∶0.5 0.312 0.312 0.625 0.625
1.0∶1.0 0.078 0.156 0.156 0.625
1.0∶2.0 0.078 0.078 0.078 0.625
1.0∶2.5 --- --- --- ---
2.0∶0.5 --- --- --- ---
1.0: 0.0 (single medicine contrast) 1.250 0.625 0.625 2.50
0.0: 1.0 (single medicine contrasts) 2.50 10.00 10.00 2.50
Annotate: 1. trichophyton was cultivated 120-168 hour, and Candida albicans is cultivated 48 hours observed results.
2. the high dissolving of "---" drug level is bad, can't observed result.
The external bacteriostasis of table 4 chlorhexidine and terbinafine variable concentrations compatibility to several frequently seen malignant bacteria (representing bacterium)
Minimal inhibitory concentration (MIC, μ g/ml)
Chlorhexidine: terbinafine
Staphylococcus aureus staphylococcus epidermidis escherichia coli bacillus subtilis
0.05∶0.2 5.00 10.00 10.00 10.00
0.1∶0.2 2.50 5.00 5.00 5.00
0.3∶0.5 0.625 1.25 1.25 1.25
0.3∶1.0 0.625 1.25 1.25 1.25
0.3∶2.0 0.625 1.25 1.25 1.25
0.3∶3.0 --- --- --- ---
0.5∶0.2 0.625 1.25 1.25 0.625
0.5∶0.5 0.625 1.25 1.25 0.625
0.5∶1.0 0.625 1.25 1.25 0.625
0.5∶2.0 0.625 1.25 1.25 0.625
0.5∶3.0 --- --- --- ---
1.0∶0.2 0.312 0.625 0.625 0.312
1.0∶0.3 0.312 0.625 0.625 0.312
1.0∶1.0 0.312 0.625 0.625 0.312
1.0∶2.0 0.312 0.625 0.625 0.312
1.0∶2.5 --- --- --- ---
2.0∶0.5 --- --- --- ---
1.0: 0.0 (single medicine contrast) 0.312 0.625 0.625 0.312
0.0: 1.0 (single medicine contrast)＞200＞200＞200＞200
Annotate: 1. cultivate 24-48 hour observed result, it is invalid that＞200 μ g/ml represent.
2. the high dissolving of "---" drug level is bad, can't observed result.
The external bacteriostasis of table 5 chlorhexidine and naftifine variable concentrations compatibility to several frequently seen malignant bacteria (representing bacterium)
Minimal inhibitory concentration (MIC, μ g/ml)
Chlorhexidine: naftifine
Staphylococcus aureus staphylococcus epidermidis escherichia coli bacillus subtilis
0.05∶0.2 5.00 10.00 10.00 10.00
0.1∶0.2 2.50 5.00 5.00 5.00
0.3∶0.5 0.625 1.25 1.25 1.25
0.3∶1.0 0.625 1.25 1.25 1.25
0.3∶2.0 0.625 1.25 1.25 1.25
0.3∶3.0 --- --- --- ---
0.5∶0.2 0.625 1.25 1.25 0.625
0.5∶0.5 0.625 1.25 1.25 0.625
0.5∶1.0 0.625 1.25 1.25 0.625
0.5∶2.0 0.625 1.25 1.25 0.625
0.5∶3.0 --- --- --- ---
1.0∶0.2 0.312 0.625 0.625 0.312
1.0∶0.3 0.312 0.625 0.625 0.312
1.0∶1.0 0.312 0.625 0.625 0.312
1.0∶2.0 0.312 0.625 0.625 0.312
1.0∶2.5 --- --- --- ---
2.0∶0.5 --- --- --- ---
1.0: 0.0 (single medicine contrast) 0.312 0.625 0.625 0.312
0.0: 1.0 (single medicine contrast)＞200＞200＞200＞200
Annotate: 1. cultivate 24-48 hour observed result, it is invalid that＞200 μ g/ml represent.
2. the high dissolving of "---" drug level is bad, can't observed result.
The external bacteriostasis of table 6 chlorhexidine and fluconazol variable concentrations compatibility to several frequently seen malignant bacteria (representing bacterium)
Minimal inhibitory concentration (MIC, μ g/ml)
Chlorhexidine: fluconazol
Staphylococcus aureus staphylococcus epidermidis escherichia coli bacillus subtilis
0.05∶0.2 5.00 10.00 10.00 10.00
0.1∶0.2 2.50 5.00 5.00 5.00
0.3∶0.5 0.625 1.25 1.25 1.25
0.3∶1.0 0.625 1.25 1.25 1.25
0.3∶2.0 0.625 1.25 1.25 1.25
0.3∶3.0 --- --- --- ---
0.5∶0.2 0.625 1.25 1.25 0.625
0.5∶0.5 0.625 1.25 1.25 0.625
0.5∶1.0 0.625 1.25 1.25 0.625
0.5∶2.0 0.625 1.25 1.25 0.625
0.5∶3.0 --- --- --- ---
1.0∶0.2 0.312 0.625 0.625 0.312
1.0∶0.3 0.312 0.625 0.625 0.312
1.0∶1.0 0.312 0.625 0.625 0.312
1.0∶2.0 0.312 0.625 0.625 0.312
1.0∶2.5 --- --- --- ---
2.0∶0.5 --- --- --- ---
1.0: 0.0 (single medicine contrast) 0.312 0.625 0.625 0.312
0.0: 1.0 (single medicine contrast)＞200＞200＞200＞200
Annotate: 1. cultivate 24-48 hour observed result, it is invalid that＞200 μ g/ml represent.
2. the high dissolving of "---" drug level is bad, can't observed result.
Compositions behind table 7 chlorhexidine and the terbinafine compatibility to three kinds of common malignant bacterias and
The bactericidal action of fungus (staphylococcus aureus, escherichia coli and Candida albicans)
5 minutes sterilizing rate (%) of medicine bacterium effect
Chlorhexidine: terbinafine
The staphylococcus aureus e coli Candida albicans
0.05∶0.2 ＞50.00 ＞50.00 ＞60.00
0.1∶0.2 ＞80.00 ＞80.00 ＞90.00
0.3∶0.5 ＞95.00 ＞95.00 ＞95.00
0.3∶1.0 ＞95.00 ＞95.00 ＞95.00
0.3∶2.0 ＞95.00 ＞95.00 ＞95.00
0.3∶3.0 ＞95.00 ＞95.00 ＞95.00
0.5∶0.2 ＞99.00 ＞99.00 99.99
0.5∶0.5 ＞99.00 ＞99.00 99.99
0.5∶1.0 ＞99.00 ＞99.00 99.99
0.5∶2.0 ＞99.00 ＞99.00 99.99
0.5∶3.0 ＞99.00 ＞99.00 99.99
1.0∶0.2 99.99 99.99 99.99
1.0∶0.3 99.99 99.99 99.99
1.0∶1.0 99.99 99.99 99.99
1.0∶2.0 99.99 99.99 99.99
1.0∶2.5 99.99 99.99 99.99
2.0∶0.5 99.99 99.99 99.99
1.0: 0.0 (single medicine contrast) 99.99 99.99 99.99
0.0: 1.0 (single medicine contrasts) 0.00 0.00 0.00
Annotate: 1. the total composition of various ratios is 100 μ g/ml when testing.
2. the high dissolving of "---" drug level is bad, can't observed result.
Compositions behind table 8 chlorhexidine and the naftifine compatibility to three kinds of common malignant bacterias and
The bactericidal action of fungus (staphylococcus aureus, escherichia coli and Candida albicans)
5 minutes sterilizing rate (%) of medicine bacterium effect
Chlorhexidine: naftifine
The staphylococcus aureus e coli Candida albicans
0.05∶0.2 ＞50.00 ＞50.00 ＞60.00
0.1∶0.2 ＞80.00 ＞80.00 ＞90.00
0.3∶0.5 ＞95.00 ＞95.00 ＞95.00
0.3∶1.0 ＞95.00 ＞95.00 ＞95.00
0.3∶2.0 ＞95.00 ＞95.00 ＞95.00
0.3∶3.0 ＞95.00 ＞95.00 ＞95.00
0.5∶0.2 ＞99.00 ＞99.00 99.99
0.5∶0.5 ＞99.00 ＞99.00 99.99
0.5∶1.0 ＞99.00 ＞99.00 99.99
0.5∶2.0 ＞99.00 ＞99.00 99.99
0.5∶3.0 ＞99.00 ＞99.00 99.99
1.0∶0.2 99.99 99.99 99.99
1.0∶0.3 99.99 99.99 99.99
1.0∶1.0 99.99 99.99 99.99
1.0∶2.0 99.99 99.99 99.99
1.0∶2.5 99.99 99.99 99.99
2.0∶0.5 99.99 99.99 99.99
1.0: 0.0 (single medicine contrast) 99.99 99.99 99.99
0.0: 1.0 (single medicine contrasts) 0.00 0.00 0.00
Annotate: 1. the total composition of various ratios is 100 μ g/ml when testing.
2. the high dissolving of "---" drug level is bad, can't observed result.
Compositions behind table 9 chlorhexidine and the fluconazol compatibility to three kinds of common malignant bacterias and
The bactericidal action of fungus (staphylococcus aureus, escherichia coli and Candida albicans)
5 minutes sterilizing rate (%) of medicine bacterium effect
Chlorhexidine: fluconazol
The staphylococcus aureus e coli Candida albicans
0.05∶0.2 ＞50.00 ＞50.00 ＞60.00
0.1∶0.2 ＞80.00 ＞80.00 ＞90.00
0.3∶0.5 ＞95.00 ＞95.00 ＞95.00
0.3∶1.0 ＞95.00 ＞95.00 ＞95.00
0.3∶2.0 ＞95.00 ＞95.00 ＞95.00
0.3∶3.0 ＞95.00 ＞95.00 ＞95.00
0.5∶0.2 ＞99.00 ＞99.00 99.99
0.5∶0.5 ＞99.00 ＞99.00 99.99
0.5∶1.0 ＞99.00 ＞99.00 99.99
0.5∶2.0 ＞99.00 ＞99.00 99.99
0.5∶3.0 ＞99.00 ＞99.00 99.99
1.0∶0.2 99.99 99.99 99.99
1.0∶0.3 99.99 99.99 99.99
1.0∶1.0 99.99 99.99 99.99
1.0∶2.0 99.99 99.99 99.99
1.0∶2.5 99.99 99.99 99.99
2.0∶0.5 99.99 99.99 99.99
1.0: 0.0 (single medicine contrast) 99.99 99.99 99.99
0.0: 1.0 (single medicine contrasts) 0.00 0.00 0.00
Annotate: 1. the total composition of various ratios is 100 μ g/ml when testing.
2. the high dissolving of "---" drug level is bad, can't observed result.
Two, clinical case report and disinfective action
The present composition, be chlorhexidine acetate and terbinafine HCl or naftifine hydrochloride or fluconazol formula proportion, in 0.1～2.0: when topical agent that 0.3～3.0 weight portion proportioning ratio is formulated and disinfectant, the disease for the treatment of cutaneous fungal infection, bacterial infection and fungus, bacteria mixed infection is had better therapeutic effect and disinfective action.
(1) clinical treatment case report
Example 1. gold medals * *, the male, 50 years old, because of itching, the inboard skin lesion companion of left side thigh portion goes to a doctor February, be diagnosed as tinea cruris.Sings and symptoms is obvious before the treatment, and fungal culture is a trichophyton.Then give compound recipe chlorhexidine acetate compositions ointment 1 week of logotype, the 2nd all sings and symptomses disappear, and fungus microscope examination and cultivation all show negative, clinical recovery.
Example 2. chrysanthemums * *, the male, 35 years old, because of skin lesion companion between the biped toe itches half a year, to itch recently and scratch, the state of an illness increases the weight of, and mixes red and swollen the prescription on individual diagnosis, is diagnosed as between toe the type tinea pedis and mixes bacterial infection.Sings and symptoms is all heavier before the treatment, and microscopy is cultivated and is alpha fungus, and antibacterial culturing is golden yellow staphylococcus.Then give compound recipe chlorhexidine acetate compositions ointment 1 week of logotype, sings and symptoms disappears substantially during drug withdrawal, and fungus microscope examination and antibacterial culturing are all negative; The 2nd week, clinical and fungus, bacteriology checking were all fully recovered.
Example 3. Huangs * *, the male, 28 years old, because of itching, preceding chest and back skin lesion companion went to a doctor in 2 years, be diagnosed as tinea versicolor.Sings and symptoms is obviously long-pending before the treatment, the fungus microscope examination positive.Then give compound recipe chlorhexidine acetate composition solution, in 1 week of logotype, sings and symptoms disappears during the 2nd all drug withdrawal, negative fungal examination, clinical recovery.
Example 4. letters * *, the male, 20 years old, because of itching, bifilar inboard skin lesion companion go to a doctor April, be diagnosed as tinea cruris.Sings and symptoms is obvious before the treatment, and fungal culture is a trichophyton.Then give compound recipe chlorhexidine acetate composition solution 1 week of logotype, the 2nd all sings and symptomses disappear, and fungus microscope examination and cultivation all show negative, clinical recovery.
5. of examples * *, the woman, 25 years old, because of itching, left neck skin lesion companion went to a doctor in 3 weeks, and the fungus microscope examination positive is diagnosed as tinea corporis, and sings and symptoms is obvious before the treatment, and fungal culture is a trichophyton.Then give the external of compound recipe chlorhexidine acetate compositions spray, 1 week of logotype, the clinical and mycology recovery from illness of the 2nd week.
Example 6. grandsons * *, the male, 20 years old, to suffer from furuncle and phyma because of left thigh and mix prescription on individual diagnosis in red and swollen 5 days, antibacterial culturing is golden yellow staphylococcus, is diagnosed as suppurative folliculitis.Sings and symptoms is obvious before the treatment, gives 1 week of compositions spray logotype then, and the 2nd all sings and symptomses disappear antibacterial culturing feminine gender, clinical recovery.
(2) on-the-spot disinfective action
Compound recipe chlorhexidine acetate compositions disinfectant solution, experiment on probation is a sterilization objects with the hands.For reducing sampling error, the 4ml of falling the sterilized water is in the palm of the hand, and the both hands raft is wiped, and does the preceding indigneous flora sampling of sterilization after drying.During sampling, with 2 * 3cm
2The cloth sheet in vitro soak in that the nertralizer that 5ml contains the PBS of 5% Tween 80,0.3% lecithin, 1% histidine and 20% calf serum is housed, push slightly to remove unnecessary neutralizer, be affixed on palm then and take off about 30 seconds, put back to former test tube.Look hand size during sterilization and fall 4-5ml in the palm of the hand, both hands are wiped mutually; Each position that maybe suction is had the napkin wiping trial work of 5ml bacterium liquid is waited medicinal liquid to dry (about 1-2 minute) back naturally and is sampled by preceding method.Sample is through suitably pouring into cultivation (37 ℃), observed result after 48 hours after the dilution.The result shows that to the carry out disinfection test of effect of 170 people this disinfectant solution is to the indigneous flora number (cfu/cm of all kinds of personnel hands
2) elimination factor is 83.64-100% (seeing Table 10), average out to 99.62% carries out statistics relatively with distilled water matched group 80 people's result of the test, differs significantly (P＜0.01), and also finding stimulates and allergic phenomena.Prove that this disinfectant solution Disinfection Effect is better, can be used as the disinfecting of hands, prevent or reduce infectious intestinal disease and suppurative bacterium and infect.
The Disinfection Effect of table 10 compound recipe chlorhexidine acetate compositions disinfectant solution adversary indigneous flora
The average average elimination factor of bacterium number in average bacterium number sterilization back before the sterilization of group test number
(sample) (cfu/cm
2) (cfu/cm
2) (%)
The disinfectant solution group:
Outpatient service 30 167.21 0.30 99.82
Operating room 70 134.20 0.26 99.81
Department of B urn 20 49.34 1.31 97.34
Hemodialysis center 30 46.64 0.19 99.59
Dining room 20 205.56 0.22 99.89
Sum 170 100.50 0.38 99.62
The distilled water group:
Outpatient service 35 185.43 92.87 49.92
Internal medicine 45 97.78 57.62 41.04
Sum 80 141.58 75.25 45.50
Annotate: two groups relatively, p＜0.01.
The specific embodiment
Embodiment 1
Antibacterials ointment of the present invention
Take by weighing chlorhexidine acetate 0.5 gram, terbinafine HCl 1.0 grams by 0.5: 1.0 formula proportion, dissolve with small amount of ethanol earlier, use the O/W dosage form, excipient is octadecanol 4 grams, stearic acid 4 grams, glyceryl monostearate 3.5 grams, vaseline 10 grams, glycerol 10 grams, and soil temperature-80 2 gram and surplus distilled water are mixed with ointment 100 grams.
Embodiment 2
Antibacterials ointment of the present invention
Take by weighing chlorhexidine acetate 0.5 gram, naftifine hydrochloride 1.5 gram raw materials by 0.5: 1.5 formula proportion, dissolve with small amount of ethanol earlier, use the O/W dosage form, excipient is octadecanol 4 grams, stearic acid 10 grams, glyceryl monostearate 5 grams, vaseline 6 grams, glycerol 10 grams, and triethanolamine 0.8 gram and surplus distilled water are mixed with ointment 100 grams.
Embodiment 3
Antibacterials solution of the present invention
Take by weighing chlorhexidine acetate 0.5 gram, fluconazol 0.5 gram by 0.5: 0.5 formula proportion, add 20ml ethanol, 20ml propylene glycol, the formulated solution 100ml of surplus distilled water.
Embodiment 4
Antibacterials tincture of the present invention
Take by weighing chlorhexidine acetate 0.3 gram, terbinafine HCl 2.0 grams by 0.3: 2.0 formula proportion, add 40ml ethanol, 20ml propylene glycol, the formulated tincture 100ml of 10ml glycerol and surplus distilled water.
Embodiment 5
Antibacterials suppository of the present invention
Take by weighing chlorhexidine acetate 1.0 grams, naftifine hydrochloride 0.5 gram, Polyethylene Glycol-1,000 73.5 grams, Polyethylene Glycol-4,000 25 grams by 1.0: 0.5 formula proportion.-4000 fusings of Polyethylene Glycol during preparation-1000 and Polyethylene Glycol are treated to add when temperature is reduced to 50 ℃ medicine (earlier medicine being ground into fine powder) and are stirred evenly, and formulated routinely suppository 100ml irritates mould etc. then.
Embodiment 6
Antibacterials spray of the present invention
Take by weighing chlorhexidine acetate 1.0 grams, terbinafine HCl or naftifine hydrochloride or fluconazol 0.6 gram by 0.6: 0.6 formula proportion, add 20ml ethanol, the formulated spray 100ml of 20ml glycerol and surplus distilled water.
Embodiment 7
Antibacterials ointment of the present invention
Take by weighing chlorhexidine acetate 0.1 gram, terbinafine HCl 0.3 gram by 0.1: 0.3 formula proportion, dissolve with small amount of ethanol earlier, use the O/W dosage form, excipient is octadecanol 4 grams, stearic acid 4 grams, glyceryl monostearate 3.5 grams, vaseline 10 grams, glycerol 10 grams, and soil temperature-80 2 gram and surplus distilled water are mixed with ointment 100 grams.
Embodiment 8
Antibacterials ointment of the present invention
Take by weighing chlorhexidine acetate 2.0 grams, naftifine hydrochloride 3.0 gram raw materials by 2.0: 3.0 formula proportion, dissolve with small amount of ethanol earlier, use the O/W dosage form, excipient is octadecanol 4 grams, stearic acid 10 grams, glyceryl monostearate 5 grams, vaseline 6 grams, glycerol 10 grams, and triethanolamine 0.8 gram and surplus distilled water are mixed with ointment 100 grams.
Embodiment 9
Antibacterials liquid disinfectant of the present invention
Take by weighing chlorhexidine acetate 0.5 gram, terbinafine HCl or naftifine hydrochloride or fluconazol 0.8 gram by 0.5: 0.8 formula proportion, add 70ml ethanol, 10ml glycerol and the formulated disinfectant 100ml of surplus distilled water.
Embodiment 9
Antibacterials disinfectant powder of the present invention
Take by weighing chlorhexidine acetate 0.5 gram, terbinafine HCl 0.8 gram by 0.5: 0.8 formula proportion, add starch 2g, the formulated disinfectant 10g of Pulvis Talci surplus.
Claims (10)
1, a kind of antibacterial combination is by the medicament that comprises that following proportioning ratio component is made, chlorhexidine acetate, terbinafine HCl or naftifine hydrochloride or fluconazol 0.1～2.0: 0.3～3.0.
2, antibacterial combination according to claim 1 is by the medicament that comprises that following proportioning ratio component is made, and chlorhexidine acetate: terbinafine HCl or naftifine hydrochloride or fluconazol are 0.3～1.0: 0.5～2.0.
3, antibacterial combination according to claim 1 is by the medicament that comprises that following proportioning ratio component is made, and chlorhexidine acetate: terbinafine HCl or naftifine hydrochloride or fluconazol are 0.5: 1.0.
4, antibacterial combination according to claim 1, described medicament can also comprise available adjuvant on the materia medica.
5, antibacterial combination according to claim 1, described medicament can be said skin on any pharmaceutics and mucosa delivery dosage form.
6, antibacterial combination according to claim 1, described medicament can also be said disinfectant on any pharmaceutics.
7, according to claim 1 or 3 described antibacterial combinations, described medicament can be ointment, ointment, solution, tincture, suppository, spray.
8, according to claim 1 or 4 described antibacterial combinations, described disinfectant can be liquid disinfectant, disinfected paper napkin, sterilization fabric, disinfectant tablet and disinfectant powder.
9, a kind of preparation method of antibacterial combination may further comprise the steps: take by weighing chlorhexidine acetate, terbinafine HCl or naftifine hydrochloride or fluconazol in described ratio, the preparation method of complying with conventional dermatologic or disinfectant prepares promptly.
10, the preparation method of antibacterial combination according to claim 7 also comprises adding any pharmaceutically available adjuvant.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031405193A CN1552314A (en) | 2003-05-27 | 2003-05-27 | Antibacterial medicinal composition |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031405193A CN1552314A (en) | 2003-05-27 | 2003-05-27 | Antibacterial medicinal composition |
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| Publication Number | Publication Date |
|---|---|
| CN1552314A true CN1552314A (en) | 2004-12-08 |
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|---|---|---|---|
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100364520C (en) * | 2006-04-24 | 2008-01-30 | 魏锐 | Tebinaifen hydrochloride suppository and its preparation method |
| CN102552504A (en) * | 2012-02-22 | 2012-07-11 | 合肥华威药业有限责任公司 | Externally applied disinfectant for treating vaginitis and preparation method thereof |
| CN108578471A (en) * | 2018-02-07 | 2018-09-28 | 合肥华盖生物科技有限公司 | A kind of medical antibacterial drug and preparation method thereof |
| CN109221292A (en) * | 2018-11-13 | 2019-01-18 | 铜仁学院 | A kind of medical disinfectant and preparation method thereof |
| CN112004532A (en) * | 2018-05-03 | 2020-11-27 | 凯尔赛德株式会社 | Composition for prevention or treatment of skin infection |
-
2003
- 2003-05-27 CN CNA031405193A patent/CN1552314A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100364520C (en) * | 2006-04-24 | 2008-01-30 | 魏锐 | Tebinaifen hydrochloride suppository and its preparation method |
| CN102552504A (en) * | 2012-02-22 | 2012-07-11 | 合肥华威药业有限责任公司 | Externally applied disinfectant for treating vaginitis and preparation method thereof |
| CN108578471A (en) * | 2018-02-07 | 2018-09-28 | 合肥华盖生物科技有限公司 | A kind of medical antibacterial drug and preparation method thereof |
| CN112004532A (en) * | 2018-05-03 | 2020-11-27 | 凯尔赛德株式会社 | Composition for prevention or treatment of skin infection |
| CN112004532B (en) * | 2018-05-03 | 2022-02-18 | 凯尔赛德株式会社 | Composition for preventing or treating skin infection |
| CN109221292A (en) * | 2018-11-13 | 2019-01-18 | 铜仁学院 | A kind of medical disinfectant and preparation method thereof |
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