CN105078881A - Method for preparing furacilin ear drops through combination of ultrasonic wave and microwave at specific frequency bands - Google Patents
Method for preparing furacilin ear drops through combination of ultrasonic wave and microwave at specific frequency bands Download PDFInfo
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- CN105078881A CN105078881A CN201510593864.3A CN201510593864A CN105078881A CN 105078881 A CN105078881 A CN 105078881A CN 201510593864 A CN201510593864 A CN 201510593864A CN 105078881 A CN105078881 A CN 105078881A
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- nitrofural
- furacilin
- dan
- microwave
- glycerol
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- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical compound NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 title claims abstract description 98
- 238000000034 method Methods 0.000 title claims abstract description 58
- 229960001907 nitrofurazone Drugs 0.000 title abstract 12
- 239000003221 ear drop Substances 0.000 title abstract 9
- 229940047652 ear drops Drugs 0.000 title abstract 9
- 230000008569 process Effects 0.000 claims abstract description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 99
- 229960000349 nitrofural Drugs 0.000 claims description 86
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 42
- 239000011521 glass Substances 0.000 claims description 37
- 150000001875 compounds Chemical class 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 14
- 238000002604 ultrasonography Methods 0.000 claims description 11
- 238000011049 filling Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000004090 dissolution Methods 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 abstract description 41
- 238000002425 crystallisation Methods 0.000 abstract description 22
- 230000008025 crystallization Effects 0.000 abstract description 22
- 230000000694 effects Effects 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 7
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 5
- 238000003860 storage Methods 0.000 abstract description 5
- 230000008859 change Effects 0.000 abstract description 4
- 239000013078 crystal Substances 0.000 abstract description 3
- 238000000870 ultraviolet spectroscopy Methods 0.000 abstract description 3
- 239000006196 drop Substances 0.000 abstract 1
- 230000000717 retained effect Effects 0.000 abstract 1
- BOJKULTULYSRAS-OTESTREVSA-N Andrographolide Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1/[C@H](O)COC1=O BOJKULTULYSRAS-OTESTREVSA-N 0.000 description 11
- ASLUCFFROXVMFL-UHFFFAOYSA-N andrographolide Natural products CC1(CO)C(O)CCC2(C)C(CC=C3/C(O)OCC3=O)C(=C)CCC12 ASLUCFFROXVMFL-UHFFFAOYSA-N 0.000 description 11
- 239000007788 liquid Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 210000000959 ear middle Anatomy 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000009254 shuang-huang-lian Substances 0.000 description 5
- 208000033809 Suppuration Diseases 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000000825 ultraviolet detection Methods 0.000 description 4
- 206010014020 Ear pain Diseases 0.000 description 3
- 206010033078 Otitis media Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 208000007176 earache Diseases 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 206010033079 Otitis media acute Diseases 0.000 description 2
- 241000193998 Streptococcus pneumoniae Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 208000024035 chronic otitis media Diseases 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 201000009259 purulent acute otitis media Diseases 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000746375 Andrographis Species 0.000 description 1
- 241001480043 Arthrodermataceae Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 240000004859 Gamochaeta purpurea Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 230000004308 accommodation Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000037358 bacterial metabolism Effects 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 235000019636 bitter flavor Nutrition 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000037304 dermatophytes Effects 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000010358 mechanical oscillation Effects 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 206010033072 otitis externa Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for preparing furacilin ear drops through combination of ultrasonic wave and microwave at specific frequency bands. The furacilin ear drops preparation is a common external local antibacterial medicine for clinical use in ear-nose-throat departments (ENT departments) of domestic hospitals. Furacilin ear drops prepared by a conventional preparation method have the following disadvantages: the furacilin ear drops are relatively poor in stability that the furacilin ear drops are easy to become dark in color in the processes of storage and clinical use and furacilin is easy to separate out brown-yellow crystals under a low-temperature condition in the winter; the furacilin ear drops, when prepared, are heated and stirred for a long time; and the content of furacilin drops in various degrees with the change of a crystallizing amount, and as a result, clinical curative effect is reduced and the furacilin ear drops become invalid. According to the furacilin ear drops prepared by the method disclosed by the invention, a process is greatly optimized. Upon retained sample observation for 24 months, the obtained product is free from phenomenon of crystallization, turbidity or the like, so that the product is quite strong in stability; and determined through ultraviolet-visible spectrophotometry, the content of the furacilin has no significant change in the period of storage, and content loss percentage is less than 1%.
Description
The application is application number: 2013103058705, and the applying date is: 2013-07-22, and name is called: " utilizing ultrasonic-microwave to prepare the method for nitrofural [Dan preparation fast ", the divisional application of Chinese invention patent.
Technical field
The present invention relates to field of pharmaceutical preparations, specifically nitrofural [Dan preparation method.
Background technology
Nitrofural [Dan is the clinical conventional local external use's antibacterials of domestic hospitals department of otorhinolaryngology, and its treatment otitis media and otitis externa determined curative effect, clinical practice is extensive.
At present, nitrofural [Dan is prepared voluntarily by each hospital usually, main component is the nitrofural of recipe quantity, ethanol and glycerol (Liu Huiyi, the preparation of nitrofural [Dan and assay, " Journal of Chinese Hospital Pharmacy "), its outward appearance is yellow clear and bright oily liquids, mildly bitter flavor.Its Main Function is interference antibacterial glycometabolic commitment, causes bacterial metabolism disorderly and dead.Its antimicrobial spectrum is comparatively wide, has antibacterial action, also have effect to anaerobe to multiple Grain-positive and negative bacterium, to bacillus pyocyaneus and Diplococcus pneumoniae active force weak, have drug resistance, to fungus to Pseudomonas and Proteus, mycete is invalid, but is still effective to mould microbial bacteriological infection.The bacteriocidal concentration of its sensitive organism is 13-20 μ g/ml, and Mlc is 5-10 μ g/ml.
At present, the preparation method of " Chinese Hospitals preparation specification " is as follows: accurately weighed nitrofural 2g is mixed homogeneously with 250ml ethanol, slowly join again in appropriate glycerol, abundant stirring makes it dissolve, heat if desired, after it dissolves completely, be chilled to room temperature, then add glycerol to full dose 1000ml, mixing, to obtain final product.
Traditional preparation methods is prepared nitrofural [Dan and be there are some shortcomings: first, and owing to relying on agitating device to provide limited shearing force, mixing time is long, and the preparation amount of preparation more than 500ml is comparatively difficult, is more difficult to the preparation amount preparing more than 1000ml.Secondly, in a series of process for preparation such as stirring, whole solution system is spacious to be put, and easily causes medicine by outside contamination.Again, the meeting that light, dirt in air and oxygen molecule, metal ion produce in process of production produces certain impact to drug quality, such as makes it darken, accelerates crystallization generation etc.To sum up, existing nitrofural [Dan poor stability, just there is the phenomenon of variable color, muddiness or crystallization in lay up period of being everlasting, especially in the winter time preparation and the easier crystallization of long-term storage.Thus reduce curative effect, therefore namely current compound method can only join i.e. use, short-term is deposited.
Summary of the invention
The nitrofural [Dan preparation that the object of the invention is to provide a kind of good stability, is easy to a large amount of production, preserves for a long time, is applicable to medical institutions, pharmacy corporation large-scale production.
The technical scheme adopted for realizing the invention object is such, and a kind of method utilizing ultrasonic-microwave to prepare nitrofural [Dan preparation fast, comprises the following steps:
1) taking recipe quantity nitrofural adds in glass container, in described glass container, add recipe quantity ethanol.In this step, under normal circumstances, nitrofural and ethanol press portion rate for (2:250); (gram) and volume (milliliter) are than being (1:125) by weight, and the prescription recorded as certain pharmacopeia is: nitrofural 2g, ethanol 250ml.As preferably, this step 1) in glass container be can open/airtight container with the glass jar of stopper or other, after containing nitrofural and ethanol, described glass container can seal.Further, before containing nitrofural and ethanol, described brown glass container and stopper thereof are through disinfecting.
2) add water in the rinse bath of ultrasonic cleaner, the described glass container filling nitrofural and ethanol is put into rinse bath.In this step, described ultrasonic cleaner can use the ultrasonic cleaner of medical field or domestic, it has the rinse bath of an accommodation cleanout fluid (the present invention can use water), the friendship that supersonic generator sends is signal frequently, is converted to friendship frequency mechanical oscillation and propagates in described cleanout fluid by transducer.
3) setting up procedure 2) described in ultrasonic cleaner, ultrasonic dissolution assisting at least 2 minutes.Namely the glass container in described rinse bath is applied to the ultrasound wave of certain frequency, its objective is and the nitrofural in described glass container is dissolved in ethanol, and affect its performance.Meanwhile, the beaker filling glycerol is put into microwave oven, by the glycerol microwave heating to 70 in described beaker DEG C ~ 75 DEG C.In the present invention, the amount of the glycerol in described beaker is recipe quantity, and described ethanol and glycerol press portion rate for (1:3), and the prescription recorded as certain pharmacopeia is: nitrofural 2g, ethanol 250ml, glycerol are about 750ml, total amount 1000ml.What deserves to be explained is, owing to having hydroxyl in glycerol molecule structure, therefore, it is possible to adopt microwave oven to carry out Fast Heating to it, reach fabulous technique effect.
4) water in the rinse bath of described ultrasonic cleaner is heated to 60 DEG C, namely make described glass container be in 60 DEG C of water-baths.By through step 3) glycerol that processes joins in the glass container filling nitrofural and ethanol, namely obtains nitrofural [Dan after mix homogeneously.As preferably, glycerol joins in the process of glass jar by this step, and described ultrasonic cleaner does not cut out, and namely described glass container is still in and step 3) in identical environment, just when adding glycerol, need the stopper opening described glass container.Further, this step is slowly joined in glass jar by glycerol, namely adopts the mode of dropping, until nitrofural all dissolve clear and bright after, the glycerol in beaker is all joined in glass jar, after jolting glass jar, covers stopper, keep in Dark Place.
As preferably, above-mentioned steps 1 ~ 4 is carried out under lucifuge condition.
The present invention has following advantage: the first, simple to operate, without the need to many lengthy and tedious processes such as electromagnetic agitation, decreases the contact with the external world, make products obtained therefrom cleaner, and preparation time is short, process; The second, significantly improve the stability of nitrofural in prescription, make the product of gained stable in properties in long time stored process, almost without situations such as content decline, crystallization, variable colors; 3rd, improve uniformity of dosage units, improve shelf index, thus enhance the safety and efficacy of clinical application.
Accompanying drawing explanation
The nonlimiting examples that the device of the invention can be provided by accompanying drawing further illustrates.
Fig. 1 is the nitrofural [Dan ultraviolet detection collection of illustrative plates adopting the inventive method to prepare;
Fig. 2 is the nitrofural [Dan ultraviolet detection collection of illustrative plates adopting traditional method to prepare;
Fig. 3 adopts the nitrofural [Dan prepared of the inventive method in microcosmic (under microscope 400 ×) the property stability observed result of first month;
Fig. 4 is microcosmic (in microscope under 400 ×) the property stability observed result of the nitrofural [Dan prepared of traditional method at first month;
Fig. 5 adopts the nitrofural [Dan prepared of the inventive method microcosmic (under microscope 400 ×) the property stability observed result of six month;
Fig. 6 is the nitrofural [Dan prepared of traditional method microcosmic (under microscope 400 ×) the property stability observed result of six month;
Fig. 7 adopts the nitrofural [Dan prepared of the inventive method microcosmic (under microscope 400 ×) the property stability observed result of the 12 month;
Fig. 8 is the nitrofural [Dan prepared of traditional method microcosmic (under microscope 400 ×) the property stability observed result of the 12 month;
Fig. 9 is the nitrofural [Dan prepared of traditional method microcosmic (under microscope 400 ×) the property stability observed result of the 24 month;
Figure 10 is the observation image of the nitrofural [Dan prepared of the traditional method crystallization of separating out at the 24 month (400 ×) under the microscope.
Detailed description of the invention
Below in conjunction with embodiment, the invention is described further, but should not be construed the above-mentioned subject area of the invention and be only limitted to following embodiment.Without departing from the technical idea of the present inventions, according to ordinary skill knowledge and customary means, make various replacement and change, all should be included in the protection domain of the invention.
Embodiment 1
Prescription forms:
Composition | Consumption |
Nitrofural | 2g |
Ethanol | 250ml |
Glycerol | About 750ml |
Full dose | 1000ml |
Take nitrofural 2g, accurately weighed, proceeded in the glass jar of tool plug.Adding 250ml ethanol mix homogeneously to described glass jar is placed in the rinse bath of ultrasonic cleaner, ultrasonic dissolution assisting 2min, namely opens described ultrasonic cleaner (ultrasonic power 500W, frequency 40KHz).Meanwhile, the 1000ml beaker filling glycerol is put into microwave oven, heat 70s with high fire (microwave output power 700W, microwave frequency 2450Hz) and make its temperature reach 70 DEG C ~ 75 DEG C.Under ultrasound condition, slowly hot glycerol is added in glass jar, continues ultrasonic 6min, period bath temperature be arranged on 60 DEG C, until nitrofural all dissolve clear and bright after, record the ultrasonic time.Add glycerol to full dose 1000ml, after jolting evenly, obtain nitrofural [Dan preparation.As preferably, the present embodiment said process carries out under lucifuge condition.
This prescription prepares 1000ml by the inventive method, total 12min consuming time (wherein ultrasonic 8min), and products obtained therefrom is clear and bright yellow oily liquid.
Embodiment 2
Prescription forms:
Composition | Consumption |
Nitrofural | 20g |
Ethanol | 2500ml |
Glycerol | About 7500ml |
Full dose | 10000ml |
Preparation method: take nitrofural 20g, accurately weighed, proceed in the glass jar of tool plug, add 2500ml ethanol mix homogeneously and be placed in ultrasonic cleaner, ultrasonic dissolution assisting 5min.Period, successively the 1000ml beaker filling recipe quantity glycerol is put into microwave oven, heat 70s with high fire (microwave output power 700W, microwave frequency 2450Hz) and make its temperature reach 70 DEG C-75 DEG C.Under ultrasound condition, slowly hot glycerol is added in glass jar, continues ultrasonic 40min, period bath temperature be arranged on 60 DEG C, until nitrofural all dissolve clear and bright after, record the ultrasonic time.Add glycerol to full dose 10000ml (namely altogether adding about 7500ml glycerol), agitation as appropriate is even, to obtain final product.Said process carries out under lucifuge condition.
This prescription prepares 10000ml by the inventive method, total 53min consuming time (wherein ultrasonic 45min), and products obtained therefrom is clear and bright yellow oily liquid.
Embodiment 3
As optimal way step 1 of the present invention) in, take after recipe quantity nitrofural adds glass container, in described glass container, add compound recipe.Compound recipe described in the present embodiment is the mixture of SHUANGHUANLIAN, andrographolide, and its ratio as in the table below.
Compound recipe nitrofural [Dan has the plurality of advantages that common nitrofural [Dan does not have, and prove through subsequent experimental of the present invention, the stability adding gained preparation of compound recipe, curative effect are obviously better than the preparation of traditional method.
The present embodiment discloses a kind of prescription composition, i.e. compound recipe nitrofural [Dan, this prescription, except principal agent nitrofural, also add the Chinese medicine compound such as SHUANGHUANLIAN and andrographolide composition, and these compositions have definite meaning to the curative effect, prevention of recurrence etc. that improve nitrofural [Dan.
Composition | Consumption |
Nitrofural | 20g |
SHUANGHUANLIAN | 150g |
Andrographolide | 100g |
Ethanol | 2500ml |
Glycerol | About 7460ml |
Full dose | 10000ml |
Preparation method: take nitrofural and be about 20g, SHUANGHUANGLIAN FENZHENJI 150g and andrographolide 100g (SHUANGHUANGLIAN FENZHENJI that the present embodiment adopts and andrographolide are commercially available, wherein, shuanghuanglian powder injection is the pure Chinese medicinal preparation used for intravenous injection obtained by Flos Lonicerae, Radix Scutellariae, Fructus Forsythiae extract, andrographolide is white crystals, system for raw material, take water-ethanol as the solid that Extraction solvent obtains with the Folium Andrographis medical material of drying).
Nitrofural, SHUANGHUANGLIAN FENZHENJI and andrographolide are proceeded in the glass jar of tool plug, add 2500ml ethanol mix homogeneously and be placed in ultrasonic cleaner, ultrasonic dissolution assisting 10min.Period, successively the 1000ml beaker filling recipe quantity glycerol is put into microwave oven, heat 70s with high fire (microwave output power 700W, microwave frequency 2450Hz) and make its temperature reach 70 DEG C-75 DEG C.Under ultrasound condition, slowly hot glycerol is added in glass jar, continues ultrasonic 45min, period bath temperature be arranged on 60 DEG C, until nitrofural, SHUANGHUANLIAN and andrographolide all dissolve clear and bright after, record the ultrasonic time.Add glycerol to full dose 10000ml, agitation as appropriate is even, to obtain final product.Said process carries out under lucifuge condition.
This prescription prepares 10000ml by the inventive method, total 60min consuming time (wherein ultrasonic 55min), and products obtained therefrom is clear and bright pale yellowish oil liquid, and getting its portion markings is sample 1, so that subsequent analysis.
Get the product that part obtains by method disclosed in embodiment 2, be labeled as sample 2.
Prepare nitrofural [Dan by the preparation method of " Chinese Hospitals preparation specification " and the formula of the present embodiment, be labeled as sample 3.
Prepare compound recipe nitrofural [Dan by the preparation method of " Chinese Hospitals preparation specification " and the formula of the present embodiment, be about to single nitrofural in " Chinese Hospitals preparation specification " and replace to the mixture of nitrofural, SHUANGHUANGLIAN FENZHENJI and andrographolide composition.Gained compound recipe nitrofural [Dan is labeled as sample 4.
1) stable content is investigated:
Choose sample 1 ~ 4 carry out first month, 12 months and 24 months time nitrofural assay, result is as follows:
The above results shows, sample 1 and 2 has similar stability.And sample 3 and 4 is difficult to long-term preservation.Particularly for compound preparation, to use conventional methods after preparation because of its poor stability, be difficult to the effect playing compound recipe.
Meanwhile, above-mentioned experiment shows no matter this method prepares nitrofural [Dan or compound recipe nitrofural [Dan, all can obtain good stability.
2) macroscopical character study on the stability:
The sample 1 prepared by the inventive method and sample 4, be yellow clear and bright oily liquids, without macroscopic muddiness and crystallization at the beginning of preparation.But the color of sample 4 is yellow oily liquid, be deeper than the color of sample 1, and have a small amount of precipitation.
After storage December, macroscopic crystallizations existing a large amount of in sample 4, and sample 1 has no the phenomenon such as crystallization and muddiness.
3) pharmacodynamic analysis
Clinical observation on the therapeutic effect:
Patient 1, man, and at the age 10, acute suppurative otitis media, otalgia, suppurates, adopt nitrofural [Dan (i.e. sample 3) prepared by the inventive method, ear is bathed, each 2 ~ 3, every day 3 times, two days later, otalgia, symptom of suppurating are alleviated to some extent, continue use three days, recovery from illness.
Patient 2, female, the age 43, chronic otitis media, otalgia, tinnitus, throughout the year with a small amount of yellow sticky discharge, prolonged do not heal (symptom comparatively patient 1 is serious).Adopt compound recipe nitrofural [Dan (i.e. sample 4) prepared by the inventive method, ear is bathed, and each 2 ~ 3, every day 3 times, after three days, all symptoms are alleviated to some extent, continues use one week, recovery from illness.
Animal experiment:
Adopt rat acute suppurative otitis media model, observe the situation after using the inventive method compound recipe nitrofural [Dan.
Model production method: by rat anesthesia, then inject streptococcus pneumoniae bacteria suspension to tympanum, wherein 1 ~ 4 day is acute infection period, tympanum is congested, and have a large amount of pus secretions, infection in 5 ~ 7 days is faded, within 7 days, later for infecting the later stage, symptom disappears substantially, and minority still has a small amount of secretions.
Change with observation post administration tympanum and tympanum: after modeling success, uses compound recipe nitrofural [Dan (experimental group uses sample 4) in acute infection period, and the normal saline adopting equivalent as a control group.Observe and find, matched group is seriously congested at acute infection period tympanum, has faint yellow to yellow pus secretions in tympanum; And the congested situation of experimental group is obviously comparatively light, pus secretory volume is less.Matched group after 14 days congested and pus disappears substantially; And experimental group in medication two days later, above-mentioned situation takes a turn for the better completely.
By above-mentioned test, demonstrating adding of SHUANGHUANLIAN can the effect of the scorching especially chronic otitis media of prevention of otitis media or auditory meatus or the recurrence of auditory meatus inflammation, can strengthen therapeutic effect with nitrofural coupling; Andrographolide has the pharmacological effect such as antibacterium and dermatophytes, antiviral, antiallergic action, adding of andrographolide has synergism to the antibacterial effect of nitrofural [Dan, the two is with nitrofural use in conjunction, can strengthen the effect to otitis media especially chronic sympton, and the stability of medicine is better.
Embodiment 4:
Prepare three batches of nitrofural [Dan preparations respectively by the method disclosed in embodiment 1 and formula, be labeled as sample 1, sample 2 and sample 3 respectively.
As a comparison, adopt traditional method, by the formula of embodiment 2, prepare nitrofural [Dan 10000ml, total 390min consuming time, products obtained therefrom is yellow oily liquid, is labeled as sample 4.
1) assay:
Precision measures the nitrofural [Dan 5.00ml in sample 1, is placed in 50ml measuring bottle, is diluted with water to scale, shake up.Precision measures diluent 2.00ml, is placed in 50ml measuring bottle, is diluted with water to scale, shake up, and according to ultraviolet visible spectrophotometry, measures absorbance, obtain ultraviolet detection collection of illustrative plates shown in accompanying drawing 1 at 375nm wavelength place.
Precision measures the nitrofural [Dan 5.00ml in sample 4, is placed in 50ml measuring bottle, is diluted with water to scale, shake up.Precision measures diluent 2.00ml, is placed in 50ml measuring bottle, is diluted with water to scale, shake up, and according to ultraviolet visible spectrophotometry, measures absorbance, obtain ultraviolet detection collection of illustrative plates shown in accompanying drawing 2 at 375nm wavelength place.
2) stable content is investigated:
Choose sample 1 ~ 4 carry out first month, 12 months and 24 months time nitrofural assay, result is as follows:
3) macroscopical character study on the stability:
The sample 1 ~ 3 prepared by the inventive method, with the sample 4 obtained by traditional method, is yellow clear and bright oily liquids, without macroscopic muddiness and crystallization at the beginning of preparation.But the color of sample 4 is yellow oily liquid, is slightly deeper than the color of sample 1 ~ 3, cause the reason of this phenomenon may be that traditional preparation methods is easily produced catabolite by illumination, oxygen molecule and metal ion catalysis and causes color burn.
After storage December, macroscopic crystallizations existing a large amount of in sample 4, and sample 1 ~ 3 has no the phenomenon such as crystallization and muddiness.Namely the product stability obtained by microwave-ultrasonic method is apparently higher than traditional preparation methods gained, and color is slightly shallow and more clarify.
4) microcosmic property stability is observed:
Choose sample 1 respectively and sample 4 is representative, under microscope (400 ×) carry out first month, the 6th month, the 12 month and the 24 month time microcosmic property stability observe.
See accompanying drawing 3 ~ 10, (Fig. 3 is sample 1 first month observed result, Fig. 4 is sample 4 first month observed result, Fig. 5 is sample 1 six month observed result, Fig. 6 is sample 4 six month observed result, Fig. 7 is sample 1 the 12 month observed result, Fig. 8 is sample 4 the 12 month observed result, and Fig. 9 is sample 1 the 24 month observed result, and Figure 10 is sample 4 the 24 month observed result):
Can be observed from Fig. 3,4, two kinds of preparation methoies are showed no crystallization at the beginning of preparation.
Can be observed from Fig. 5,6, store under the same conditions after six months, though all without the visible crystallization of naked eyes, under amplification 400 × condition, traditional preparation methods has a small amount of crystallization, and no matter microwave-ultrasonic method is showed no crystallization under perusal or microscope.
Can be observed from Fig. 7,8, store after 12 months under the same conditions, traditional preparation methods has a large amount of macroscopic yellow crystal and separates out.And microwave-ultrasonic method is without macroscopic crystallization, and also there are no crystallization under amplification 400 × condition.
Can be observed from Fig. 9,10, store after 24 months under the same conditions, the crystallization quantity that traditional preparation methods is separated out increases further, and volume increases further, and crystallization color gradually becomes yellowish-brown.And microwave-ultrasonic method is still without macroscopic crystallization, and have not yet to see crystallization under amplification 400 × condition.
According to the relevant regulations of " Chinese Hospitals preparation specification ", the effect duration of nitrofural [Dan is 12 months, and nitrofural [Dan prepared by the present invention is at interim the stable of outward appearance and content that keep of the reserved sample observing reaching 24 months always, reach the relevant regulations about external preparation in " Chinese Pharmacopoeia " completely.Invention increases the shelf index of nitrofural [Dan, make the suitability for industrialized production of this medicine become possibility.
Claims (6)
1. use special frequency channel ultrasound wave and the microwave combined method preparing nitrofural [Dan, it is characterized in that, comprise the following steps:
1) taking recipe quantity nitrofural adds in glass container, in described glass container, add recipe quantity ethanol;
2) add water in the rinse bath of ultrasonic cleaner, the described glass container filling nitrofural and ethanol is put into rinse bath; Frequency 40KHz;
3) setting up procedure 2) described in ultrasonic cleaner, ultrasonic dissolution assisting at least 2 minutes; Meanwhile, the beaker filling glycerol is put into microwave oven, by the glycerol microwave heating to 70 in described beaker DEG C ~ 75 DEG C; Microwave frequency 2450Hz;
4) water in the rinse bath of described ultrasonic cleaner is heated to 60 DEG C, the glycerol through step 3) process is joined in the glass container filling nitrofural and ethanol, namely obtain nitrofural [Dan.
2. according to claim 1ly a kind ofly use special frequency channel ultrasound wave and the microwave combined method preparing nitrofural [Dan, it is characterized in that: in step 1), described glass container is the brown glass tank with stopper.
3. according to claim 2ly a kind ofly use special frequency channel ultrasound wave and the microwave combined method preparing nitrofural [Dan, it is characterized in that: in step 4), joined by glycerol in the process of tool plug brown glass tank, described ultrasonic cleaner does not cut out.
4. according to claim 3ly a kind ofly use special frequency channel ultrasound wave and the microwave combined method preparing nitrofural [Dan: in step 4), glycerol is slowly joined in brown glass tank, until nitrofural all dissolve clear and bright after, glycerol remaining in beaker is all joined in brown glass tank, after stirring or jolting make solution mix homogeneously, cover stopper, keep in Dark Place.
5. a kind of according to 1 ~ 4 any one claim uses special frequency channel ultrasound wave and the microwave combined method preparing nitrofural [Dan, it is characterized in that: in step 1), take after recipe quantity nitrofural adds glass container, in described glass container, add compound recipe.
6. a kind of according to 1 ~ 4 any one claim uses special frequency channel ultrasound wave and the microwave combined method preparing nitrofural [Dan, it is characterized in that: step 1 ~ 4 are carried out under lucifuge condition.
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CN201510593864.3A Active CN105078881B (en) | 2013-07-22 | 2013-07-22 | It is a kind of to use special frequency channel ultrasonic wave and the microwave combined method for preparing nitrofurazone auristilla |
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MOHINDRA J K等: "Increased Cell Killing by Metronidozole and Nitrofurazone of Hypoxic Compared to Aerobic Mammalian Cells", 《CANCER REARCH》 * |
刘辉义: "呋喃西林滴耳液的配制与含量测定", 《中国医院药学杂志》 * |
寿张轩等: "硼酸滴耳液的制备方法改进", 《中国药房》 * |
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