CN104083324B - Veterinary suspoemulsion containing rifaximin as well as preparation method and application thereof - Google Patents
Veterinary suspoemulsion containing rifaximin as well as preparation method and application thereof Download PDFInfo
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- CN104083324B CN104083324B CN201410329427.6A CN201410329427A CN104083324B CN 104083324 B CN104083324 B CN 104083324B CN 201410329427 A CN201410329427 A CN 201410329427A CN 104083324 B CN104083324 B CN 104083324B
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Abstract
The invention belongs to the field of veterinary antibiotic medicaments, and particularly relates to a suspoemulsion containing rifaximin as well as a preparation method and application of the suspoemulsion in preventing and treating mastitis infection of cow in the dry period. The suspoemulsion is prepared from rifaximin, an oil phase, an emulsifier and a water phase.
Description
Technical field
The invention belongs to veterinary antibiotic drug world, and in particular to a kind of suspension emulsion of rifaximin, preparation method, and
Its application in prevention and treatment mammitis of dairy cattle during nonlactating infection.
Background technology
Rifaximin (Rifaximin) is Ryfamycin derivative, is first non-amino glucoside enteron aisle antibiotic.Profit
Good fortune former times, bright effect was strong, has a broad antifungal spectrum, to the aurococcus in gram-positive aerobic bacteria, MRSE and
Streptococcus fecalis；To Salmonella, Escherichia coli, Shigella, enterocolitis in the irregular oxygen bacterium of Gram-negative
Yersinia ruckeri, coccus；Bacteroides in gram-negative anaerobic bacteria has high activity.
Rifaximin suppresses bacterium by the irreversible combination of b- subunits with DNA of bacteria-dependenc RNA polymerase
The synthesis of RNA, the synthesis of final suppression bacterioprotein.Because the combination of itself and enzyme is irreversible, so its activity is right
The bactericidal activity of sensitive bacteria.Research to rifaximin antibacterial activity shows that rifaximin has same extensive with rifamycin
Antimicrobial spectrum, to most Gram-positives and gramnegative bacterium, including the infection of aerobic bacteria and anaerobic bacteria has sterilized work
With.Rifaximin is ratified for treating mammitis of dairy cattle during nonlactating in calendar year 2001 in Australia.
Rifaximin is widely adopted in people's medication, and formulation has been listed the agent such as tablet, parenteral solution, dry-mixed outstanding, capsule
Type.
Chinese patent CN102716168A discloses a kind of rifaximin with dandelion compound suspension formulations and preparation side
Method, is made up of following component and percentage by weight：Rifaximin 0.5-1%, dandelion extract 5-5.5%, thickener pool Lip river
Husky nurse 4074-6%, adhesion agent isopropyl myristate 1-2%, antioxidant BHT 0.05-0.1%, remaining be pharmaceutical grade castor-oil plant
Oil, altogether 100%.Chinese patent CN102218078A discloses a kind of compound rifaximin suspension containing montmorillonite and preparation
Method, is made up of following component and percentage by weight：Rifaximin 5-15%, montmorillonite 7.5-22.5%, suspending agent 0.5-
2%th, surfactant 0.2-1%, deflocculant 0.2-1%, remaining is water.
Above-mentioned supensoid agent technology has used the compositions such as traditional Chinese medicine ingredients and montmorillonite, castor oil, makes preparation become difficult, institute
Obtain product to be difficult to mix, demulsifying phenomenon occur, medicament contg is also unstable, and injection uses hurt like hell, and in addition castor oil has
Certain toxicity, is unfavorable for the preparation of injection.
Suspension emulsion (Suspoemulsion, SE), is by water-fast solid drugs, i.e. solid suspension and emulsion
The suspension emulsus system being mixed to form.Suspension emulsion is a kind of three-phase mixed system being made up of oil phase, water phase and solid phase, and it is not only
Characteristic with supensoid agent and emulsion, but also with itself special performance.(1) suspension emulsion has the effect of one multiple-effect.It is outstanding
Emulsion can simultaneously contain plurality of active ingredients, several active components can be contained in the not homophase in system, so can be with
Play one multiple-effect function.For example in oil-in-water type suspension emulsion, emulsion can contain one or more active material, wherein having
A little components can be water miscible, and some active components can be oil-soluble, and both can contain with solid particle shape in continuous phase
The active ingredient that formula is present, can also contain water-soluble actives.(2) suspension emulsion has compared with high bioactivity.Due to suspension emulsion
Plurality of active ingredients can be simultaneously contained, makes that there is collaboration or each component of enhancement effect to be present in same system such that it is able to
The biologically active of increase medicine.(3) suspension emulsion can delay or Drug controlled release, can be oiliness medicine or pressed powder medicine
Make suspension emulsion formulation, play long-acting, while it also avoid preparing liquid dosage form needing to use lacking for organic solvent
Point, reduces product cost and toxicity, especially Pesticidal products, it is to avoid using organic solvent and dust medicine environment is caused
Pollution.(4) suspension emulsion is easy to use, can by oral administration, injection etc. approach use.
It is that rifaximin is prepared into into suspension emulsion, the present invention has carried out substantial amounts of research, has screened substantial amounts of medicinal reagent,
Finally found that a kind of toxicity is low, good stability, nonirritant rifaximin suspension emulsion.
The content of the invention
It is an object of the invention to provide a kind of rifaximin injects suspension emulsion.
The suspension emulsion of the rifaximin of the present invention, it is characterised in that including following component：
Described oil phase preferably vegetable oil, the vegetable oil is selected from：Soybean oil, cottonseed oil, peanut oil, sesame oil, corn oil,
The mixture of one or more any ratios of tea oil, sunflower oil, castor oil or olive oil.
Described emulsifying agent includes naturally occurring emulsifying agent and surfactant-based emulsifying agent.Naturally occurring emulsifying agent is selected from：It is Arabic
Glue, tragacanth, gelatin, apricot glue, lecithin, soybean lecithin.The preferred non-ionic surface active of surfactant-based emulsifying agent
Agent, is selected from：Fatty glyceride, sucrose fatty ester, polyoxyethylene sorbitan fatty acid ester (Tween is serial), dehydration
Span (Span is serial), polyoxyethylene fatty acid ester (Myrij is serial), polyoxyethylene aliphatic alcohol ether (Brij systems
Row), castor oil polyoxyethylene ether (EL is serial), one or more any ratios of poloxamer (Poloxamer) mix
Compound.
The present invention also provides the preparation method of rifaximin suspension emulsion, the method comprising the steps of：
(1) rifaximin and vegetable oil are taken, by stirring, oil phase is obtained；
(2) take emulsifying agent and add appropriate water for injection stirring and dissolving, water phase is obtained；
(3) water is added to into oil phase, by colloid mill, is well mixed；
(4) full dose is added water to, stirs evenly the suspension emulsion for obtaining final product rifaximin.
The rifaximin suspension emulsion of the present invention, may also include as needed auxiliary agent；The auxiliary agent includes emulsifying agent stabilizer,
Suspending agent, antioxidant, preservative, flavouring.The addition of auxiliary agent determines according to pharmaceutical technology field routine techniques.
Wherein, described emulsifying agent stabilizer can improve the viscosity of emulsion, strengthen emulsification film strength, prevent emulsion droplet from closing
And, including increase the methylcellulose of water phase viscosity, sodium carboxymethylcellulose, hydroxypropyl cellulose, sodium alginate, agar, Ah
Draw the cetanol of primary glue, tragacanth, xanthans, pectin and increase oil phase viscosity, beeswax, glycerin monostearate, stearic acid,
Stearyl alcohol etc..
Described suspending agent is selected from：Sodium carboxymethylcellulose, methylcellulose, Arabic gum, xanthans, polyvinyl pyrrole
Polyethylene glycol, the rilanit special of alkanone, molecular weight more than 1000.
Described antioxidant is selected from, lipophile antioxidant and water soluble antioxidants, preferred pyrosulfite, sulphite,
Thiocarbamide, gallic acid and its esters, BHA, BHT, tocopherol, ascorbic acid.
Described preservative is selected from：P-hydroxybenzoate, benzyl alcohol, methaform, Phenoxyethanol, phenol derivmives blend life
Thing, benzoic acid, sorbic acid and their basic salt, described quaternary ammonium compound such as benzalkonium bromide and benzyl rope chloramines.
Using auxiliary agent, the rifaximin suspension emulsion, including following component：
Its preparation method, comprises the following steps：
(1) rifaximin and vegetable oil are proportionally measured, by stirring, oil phase is obtained；
(2) weigh emulsifying agent and add a small amount of water for injection stirring and dissolving, water phase is obtained；
(3) water is added to into oil phase, by colloid mill, is well mixed；
(4) auxiliary agent is added, is ground；
(5) full dose is added water to, stirs evenly the suspension emulsion for obtaining final product rifaximin.
Present invention simultaneously provides the rifaximin suspension emulsion of the present invention is in the veterinary drug for preparing treatment mammitis of dairy cattle during nonlactating
In application.
Currently preferred formula composition is as follows：
Most preferably formula composition of the invention is as follows：
Preparation method is：
Rifaximin, soybean oil are taken, by colloid mill, rifaximin is dispersed in soybean oil；Addition Tween 80,
Sorbester p17, methylcellulose rubber cement and appropriate water for injection, by colloid mill, are well mixed；Auxiliary agent is added, full dose is added water to,
Stir evenly and obtain final product the suspension emulsion containing rifaximin.
Most preferably formula of the invention is obtained through screening, and screening process is as follows：
With the suspension emulsion and Chinese patent CN102716168A of the embodiment of the present invention 1, in Chinese patent CN102218078A
Rifaximin supensoid agent carry out stability control experiment, experimental result is as follows：
With the suspension emulsion and Chinese patent CN102716168A of the embodiment of the present invention 1, in Chinese patent CN102218078A
Rifaximin supensoid agent carry out slow release effect control experiment, experimental result is as follows：
With the suspension emulsion and Chinese patent CN102716168A of the embodiment of the present invention 1, in Chinese patent CN102218078A
Rifaximin supensoid agent in injection carry out local irritation control experiment, experimental result is as follows：
Slow release effect detection data is as follows in the animal body of the embodiment of the present invention 1：
| The rifaximin blood concentration of the embodiment of the present invention 1 | |
| 2 hours | 0 |
| 4 hours | 0 |
| 6 hours | 0 |
| 8 hours | 0 |
| 10 hours | 0 |
| 12 hours | 0 |
| 14 hours | 0 |
| 16 hours | 0 |
| 18 hours | 0 |
| 20 hours | 0 |
| 22 hours | 0 |
| 24 hours | 0 |
The maximum advantage of rifaximin is not absorb in vivo, and after cow breast injection, medicine of the rifaximin in milk is dense
Degree detection method is detected that milch goat is extracted by acetonitrile using HPLC-MS/MS, plus isopropanol revolving, finally uses 2mL30%
Aqueous acetonitrile solution, 0.2 μm of membrane filtration of Jing, using liquid chromatography tandom mass spectrometry determination.
The invention has the beneficial effects as follows：
The rifaximin suspension emulsion of the present invention, better stability of preparation, drug effect keeps constant with bulk drug, by the test of pesticide effectiveness
Show, single administration, the whole dry milk phase can be prevented to infect, with obvious slow release effect, can be applicable to prepare rifaximin
Ejection preparation for animals, the preparation method of the suspension emulsion is simple, low cost of manufacture.
The rifaximin suspension emulsion prepared with this method ensure that rifaximin suspension emulsion crystal formation and rifaximin bulk drug
Crystal formation is consistent, it is ensured that the drug effect of rifaximin suspension emulsion, and gained suspension stability is good, has good slow release effect,
Heighten the effect of a treatment, improve the stability of medicine, have long-acting.
Specific embodiment
The present invention is further described with reference to specific embodiment.
Embodiment 1 prepares each component according to following ratio：
Preparation method is：
Rifaximin, soybean oil are measured according to prescription, by colloid mill, rifaximin is dispersed in soybean oil；
Tween 80, sorbester p17, methylcellulose rubber cement and the appropriate water for injection of recipe quantity are added, by colloid mill, is well mixed；Plus
Enter the auxiliary agent of recipe quantity, add water to full dose, stir evenly and obtain final product the suspension emulsion containing rifaximin.
Embodiment 2 prepares each component according to following ratio：
Preparation method is：
Recipe quantity rifaximin and auxiliary material are taken, is prepared according to above-mentioned preparation method, obtain final product rifaximin suspending agent.
Embodiment 3 prepares each component according to following ratio：
Preparation method is：
Recipe quantity rifaximin and auxiliary material are taken, is prepared according to above-mentioned preparation method, obtain final product rifaximin suspending agent.
The rifaximin suspension emulsion that the present invention is prepared, better stability of preparation, good biocompatibility, slow release effect shows
Write, the ejection preparation of rifaximin can be prepared into using existing conventional techniques.
Claims (2)
1. a kind of rifaximin suspension emulsion, formula composition is as follows：
Preparation method is：
Rifaximin, soybean oil are taken, by colloid mill, rifaximin is dispersed in soybean oil；Add Tween 80, sapn
80th, methylcellulose rubber cement and appropriate water for injection, by colloid mill, are well mixed；Add propylgallate, para hydroxybenzene
Methyl formate and propylparaben, add to the full amount of water for injection, and stir evenly and obtain final product the suspension emulsion containing rifaximin.
2. a kind of preparation method of rifaximin suspension emulsion, step is as follows：
Formula composition is as follows：
Preparation method is：
Rifaximin, soybean oil are taken, by colloid mill, rifaximin is dispersed in soybean oil；Add Tween 80, sapn
80th, methylcellulose rubber cement and appropriate water for injection, by colloid mill, are well mixed；Add propylgallate, para hydroxybenzene
Methyl formate and propylparaben, add to the full amount of water for injection, and stir evenly and obtain final product the suspension emulsion containing rifaximin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410329427.6A CN104083324B (en) | 2014-07-10 | 2014-07-10 | Veterinary suspoemulsion containing rifaximin as well as preparation method and application thereof |
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|---|---|---|---|
| CN201410329427.6A CN104083324B (en) | 2014-07-10 | 2014-07-10 | Veterinary suspoemulsion containing rifaximin as well as preparation method and application thereof |
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| CN104083324B true CN104083324B (en) | 2017-05-10 |
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Families Citing this family (3)
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| CN104382923A (en) * | 2014-10-27 | 2015-03-04 | 郑州百瑞动物药业有限公司 | Lincomycin hydrochloride breast injectant for dairy cow and preparation method thereof |
| CN108542881A (en) * | 2018-04-28 | 2018-09-18 | 黑龙江省兽医科学研究所 | A kind of rifaximin microemulsion and preparation method thereof |
| CN110812326B (en) * | 2019-11-04 | 2022-04-22 | 黑龙江省农业科学院畜牧兽医分院 | Simvastatin suspension emulsion and preparation method and application thereof |
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| ITMI20032144A1 (en) * | 2003-11-07 | 2005-05-08 | Alfa Wassermann Spa | REFLEXIMINE POLIMORPHIC FORMS, PROCESSES TO OBTAIN THEM AND |
| ES2747259T3 (en) * | 2006-03-09 | 2020-03-10 | Salix Pharmaceuticals Inc | Anti-rectal preparation of rifaximin |
| CN101444484A (en) * | 2008-12-24 | 2009-06-03 | 华南农业大学 | Suspension emulsion of florfenicol, preparation method and application thereof |
| CN101862294B (en) * | 2010-06-22 | 2012-08-22 | 华南农业大学 | Ivermectin suspending agent, preparation method and application thereof |
| CN102274221B (en) * | 2011-06-30 | 2012-11-07 | 山东恩康药业有限公司 | Veterinary compound rifaximin liposome medicament and preparation method thereof |
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Inventor after: Jiang Yihai Inventor after: Yang Li Inventor after: Lu Xiangling Inventor after: Wang Haiyan Inventor after: Wu Lili Inventor after: Zhang Zhidong Inventor after: Zhao Yongda Inventor after: He Qianqian Inventor after: Che Yuanyuan Inventor after: Wang Yanling Inventor after: You Jia Inventor after: Li Mingju Inventor after: Zhou Dawei Inventor after: Wang Xiaoyi Inventor before: Zhao Yongda Inventor before: Jiang Yihai Inventor before: He Qianqian Inventor before: Che Yuanyuan |
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Effective date of registration: 20170308 Address after: 266109 Shandong city of Qingdao province high tech Zone Songyuan Road No. 17 Qingdao City Industrial Research Institute C1 District 307 Applicant after: Qingdao National Engineering Technology Research Center Co., Ltd. Address before: Miao road Laoshan District 266100 Shandong city of Qingdao province Shandong No. 29 high building 12F06 Applicant before: QINGDAO VLAND BIOLOGICAL CO., LTD. |
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