CN101653415A - Florfenicol liposome preparation and preparation method thereof - Google Patents
Florfenicol liposome preparation and preparation method thereof Download PDFInfo
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- CN101653415A CN101653415A CN200910013571A CN200910013571A CN101653415A CN 101653415 A CN101653415 A CN 101653415A CN 200910013571 A CN200910013571 A CN 200910013571A CN 200910013571 A CN200910013571 A CN 200910013571A CN 101653415 A CN101653415 A CN 101653415A
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Abstract
The invention provides a preparation method of florfenicol liposome preparation, comprising the following steps of placing 2-6kg of florfenicol and 40g of sodium benzoate into a 20L flask; adding 2-15L of propylene glycol; beating evenly in a colloid grinder; adding 1-6kg of soybean oil for injection; placing into the colloid grinder for evenly beating again; adding 400-600g of soybean lecithin and beating evenly in the colloid grinder; adding 0.5-1L of water for injection and beating repeatedly and evenly in the colloid grinder; adding 40L of water for injection and using the colloid grinderfor evenly beating; placing in an ATS high-pressure homogenizer, and carrying out repeated homogeneity under the pressure of 800-1200bar; and obtaining the finished product when latex is below 10 nanometers. The invention has fine preparation property and targeting performance, can improve curative effect, and has the advantages of long efficacy, reduced medical toxicity, improved medical stability and the like.
Description
Technical field
The present invention relates to a kind of Liposomal formulation, particularly relate to a kind of preparation method of florfenicol liposome preparation.
Background technology
Liposome is a kind of targeted drug carrier, belongs to a kind of novel form of targeting drug delivery system.It can be embedded in diameter with drug powder or solution is in the nano level microgranule, this microgranule has the class cellularity, enter the autoimmune function that is mainly activated body in the human or animal body by reticuloendothelial system phagocytic, and the interior distribution of the body that changes encapsulated medicine, drug main will be put aside in histoorgans such as lung, spleen, liver and bone marrow, thereby improve the therapeutic index of medicine, reduce the toxicity of the therapeutic dose and the reduction medicine of medicine.The drug level of florfenicol liposome of the present invention in the chicken alveolar than high 8-16 in its hetero-organization doubly.With the oil emulsion of CN10144484A essential distinction is arranged, its breast grain wants little up to ten thousand times.Liposome is dispersed in phospholipid by Britain scholar Bangham and Standish at first and finds when carrying out electron microscopic observation in the water.Phospholipid is dispersed in and forms multilamellar vesicle, every layer of bilayer that is lipid in the water naturally; Separated by water between vesicle central authorities and each layer, bilayer thickness is about 4 nanometers.Afterwards, this bimolecular folliculus with similar biofilm structure was called liposome.People such as Britain Lai Men began liposome is used for pharmaceutical carrier in 1971.Liposome is to be formed for film material enclose by phospholipid, cholesterol etc.These two kinds of compositions still do not form the basic substance of liposome bilayer, and itself have very important physical function yet.When making the film material of liposome with phospholipid and cholesterol, must earlier lipoids be dissolved in wiring solution-forming in the organic solvent, organic solvent is removed in evaporation then, form uniform lipoids thin film on wall, this thin film is made up of the bilayer that phospholipid and cholesterol mixed molecules space align.By structure and particle diameter, liposome can be divided into unilamelar liposome, multilamelar liposome, contain the liposome of surfactant.By performance, liposome can be divided into general liposome (comprising above-mentioned unilamelar liposome, multilamelar liposome and multiphasic liposomes etc.), property liposome, thermal sensitive liposome, PH sensitive liposome body, ultrasound wave sensitive liposome body, photosensitive liposome and magnetic liposome etc.Press charge, liposome can be divided into neutral fat plastid, elecrtonegativity liposome, electropositive liposome.
Florfenicol (Florfeniol), chemical name: [R--(R1.T)]-2,2-two chloro-N-{ methyl fluorides)-2-hydroxyl-2-[4-(sulfonyloxy methyl) phenyl] ethyl } acetamide, molecular formula: C
12H
14Cl
2FNO
4S, molecular weight: 358.211863, character: this product is white or off-white color crystalline powder, odorless, bitter in the mouth.Very easily dissolving is dissolved in methanol in dimethyl formamide, and is molten in the glacial acetic acid part omitted, micro dissolution in water or chloroform.Prove after deliberation: the main group that causes aplastic anemia in the chloromycetin chemical constitution is the para-position nitro on the aromatic rings.Florfenicol then is with CH
3SO
4Replaced NO
2Group makes chemical constitution that change take place, so be used for not producing in the animal body untoward reaction of aplastic anemia.This is the broad spectrum antibiotic of the special-purpose chloromycetin of a kind of new veterinary successfully developed in the later stage eighties in last century.By the initiative of the earlier clever Bao Ya company of the U.S..Nineteen ninety, Norway in 1993 ratified the furunculosis of this medicine treatment salmon first in Japan listing, nineteen ninety-five France, Britain, Austria, Mexico and Spain's approval be used for the treatment of cattle respiratory system bacterial disease.Also ratify to be used as feed additive, prevention and the bacterial disease (Qiu Yinsheng etc., 1996) for the treatment of pig of pig in Japanese and Mexico.At present in the Asia, more than 20 country's listings in Europe, America, China has also passed through examining of this medicine.The clinical bacterial disease that is used for animals such as Fish, cattle, pig goes through.Florfenicol is a chloromycetin animal specific broad ectrum antibiotic of new generation, has the characteristics such as wide, safe and efficient that distribute in the antibiotic wide spectrum, good absorbing, body, and is remarkable to the fowl bacterial disease therapeuticing effect due to the sensitive organism.
Summary of the invention
Purpose of the present invention, provide the preparation method of the medicine new support that a kind of broad spectrum antibiotic fluorine Buddhist nun for animals examines, promptly the fluorine Buddhist nun examines Liposomal formulation, to increase substantially the drug effect that the fluorine Buddhist nun examines medicine, as the respiratory system diseases such as airsacculitis of chicken, lower drug toxicity and improve the medicine stability energy.
The technical scheme that adopts is:
A kind of florfenicol liposome preparation comprises following component:
Hold percentage ratio in anharmonic ratio: florfenicol medicine 5-15%, fat phase 2.5-15%, film material 1-1.5%, wetting agent 5-38.5% and antiseptic 0.1-0.3%, surplus is a water.
Above-mentioned florfenicol liposome preparation, be to be the film material with soybean phospholipid or lecithin, soybean oil, olive oil, Semen Allii Tuberosi wet goods are the fat phase, ethanol, propylene glycol, Polyethylene Glycol, isopropyl alcohol etc. are wetting agent, antiseptic adopts sodium benzoate, adopt the florfenicol nanoscale emulsion of high pressure homogenizer preparation, granularity is less than 10 nanometers.
A kind of preparation method of florfenicol liposome preparation, be that the fluorine Buddhist nun is examined 2-6kg, sodium benzoate 40g, put into the beaker of 20L, add propylene glycol 2-15L, put beat in the colloid mill even after, add injection soybean oil 1-6kg, put again to beat in the colloid mill and spare, add soybean phospholipid 400-600g again, beat evenly with colloid mill, add injection water 0.5-1L, beat even repeatedly with colloid mill, add the injection water again to 40L, beat evenly with colloid mill, place the ATS high pressure homogenizer again, homogenizing repeatedly under 800-1200bar pressure, emulsion reaches below 10 nanometers, is finished product.
The invention has the advantages that:
1, good preparation nature:
The used fat material of preparation liposome toxicity is little, and biocompatibility is good, does not have immunoreation.
2, improve curative effect:
Florfenicol nano-lipid precursor emulsion uses proof through ten batches of 30,000 chickens, and is better to the airsacculitis curative effect of chicken.
3, have good targeting:
The targeting of liposome has four types:
1) passive (natural) targeting: natural targeting is the basic feature of liposome intravenously administrable.Be owing to liposome is engulfed distribution characteristics in the body that produces by macrophage as external foreign body.This feature of liposome is widely used in the treatment of lung, liver tumor etc. and prevents the diffusion and the transfer of lymphsystem tumor etc.
2) compartment targeting: the compartment targeting refers to liposome and enters by different modes of administration and can have targeting to different parts after the human body.
3) Physical Target tropism: in the design process of liposome, utilize the change of the physical factor of site of action or chemical factor and change the permeability of adipose membrane, cause that the liposome selectivity discharges medicine, thereby reach the purpose of target administration.The factor of this physics or chemistry comprises that local pH changes diseased region variations in temperature, the variation in magnetic field etc.The most successful example of physics target liposomes design at present is the responsive to temperature liposome.
4) targeting initiatively: this targeting is to connect certain identification molecule on liposome, promptly so-called part by the ligand molecular specificity single-mindedly with the corresponding molecular action on target cell surface, make liposome in the target region release.Common part has: sugar, lectins, peptide hormone, little hapten, antibody and other protein.
4, long-acting:
Pharmaceutical pack is wrapped in the liposome, and can be reduced in the tissue diffusion and slowly in blood, discharge medicine, thus prolong drug action time.
5, lower drug toxicity:
The lipid physical ability optionally is distributed in some tissue and organ, increases medicine to lymphoid directionality, improves the treatment concentration of medicine at target site.Especially to cancer therapy drug, can make it optionally to kill and wound cancerous cell or anticancer, to the obviously reduction or the harmless effect of toxicity of normal structure, cell.Surface of liposome character is changed,, can improve the selectivity of medicine, thereby also reduce toxicity, reduced untoward reaction the target area as size, surface charge, tissue specificity antibody etc.
6, improve medicine stability:
The nanoscale emulsion does not precipitate, and good stability can be miscible with the water arbitrary proportion.The medicine of some unsettled easy oxidations is made after the liposome,, can be significantly improved its stability because drug encapsulation in liposome, is subjected to the protection of class lipid bilayer membrane.After simultaneously in entering body, because the protection of liposome membrane, medicine can be avoided body enzyme system and immune degraded.
The specific embodiment
Embodiment one
A kind of florfenicol liposome preparation holds percentage ratio in anharmonic ratio: be by florfenicol 5%, sodium benzoate 0.1%, olive oil 2.5%, soybean phospholipid 1%, ethanol 5%, add water 86.4% and be prepared into, below granularity 10 nanometers.
Embodiment two
A kind of florfenicol liposome preparation holds percentage ratio in anharmonic ratio: be to be prepared into by florfenicol 10%, sodium benzoate 0.2%, soybean oil 7.5%, Semen sojae atricolor phosphorus matter 1%, isopropyl alcohol 30% and water 51.3%, below granularity 10 nanometers.
Embodiment three
A kind of florfenicol liposome preparation holds percentage ratio in anharmonic ratio: be to be prepared into by florfenicol 15%, sodium benzoate 0.3%, soybean oil 13%, lecithin 1.5%, propylene glycol 38% and water 32.2%, below granularity 10 nanometers.
Embodiment four
A kind of florfenicol liposome preparation is by florfenicol 4kg, propylene glycol 12L, injection soybean oil 4kg, soybean phospholipid 600g, sodium benzoate 40g, adds the injection water and is mixed with to 40L, and the breast grain reaches below 10 nanometers.
Embodiment five
A kind of florfenicol liposome preparation is by florfenicol 2kg, sodium benzoate 40g, propylene glycol 8L, injection soybean oil 4kg, soybean phospholipid 400g, adds the injection water and be mixed with to 40L, and the breast grain reaches below 10 nanometers.
Embodiment six
The preparation method of florfenicol liposome is:
With florfenicol 4.0kg, sodium benzoate 40g puts into the beaker of 20L, add propylene glycol 12L and stir evenly, put beat in the colloid mill even after, adding injection soybean oil 4kg, put again to beat in the colloid mill and spare, add soybean phospholipid 600g again, beat even with colloid mill, add injection water 0.5-1L, beat evenly with colloid mill repeatedly, be settled to 40L with water for injection, beat even with colloid mill, place homogenizing under the ATS high pressure homogenizer 800-1500bar pressure again, the breast grain reaches below 10 nanometers, and florfenicol content is 10%.
Embodiment seven
The preparation method of florfenicol liposome:
With florfenicol 2.0kg, sodium benzoate 40g puts into the beaker of 20L, add propylene glycol 8L and stir evenly, put beat in the colloid mill even after, adding injection soybean oil 6kg, put again to beat in the colloid mill and spare, add soybean phospholipid 400g again, beat even with colloid mill, add injection water 0.5-1L, beat evenly with colloid mill repeatedly, be settled to 40L with water for injection, beat even with colloid mill, place homogenizing under the ATS high pressure homogenizer 800-1200bar pressure again, the breast grain reaches below 10 nanometers, and florfenicol content is 5%.
Claims (4)
1, a kind of florfenicol liposome preparation is characterized in that:
Hold percentage ratio in anharmonic ratio, component comprises florfenicol medicine 5-15%, fat phase 2.5-15%, film material 1-1.5%, wetting agent 5-38.5% and antiseptic 0.1-0.3%, and surplus is a water, and granularity is below 10 nanometers; Described fat comprises soybean oil, olive oil or Semen Allii Tuberosi wet goods mutually; Described film material is soybean phospholipid or lecithin, and described wetting agent comprises ethanol, propylene glycol, Polyethylene Glycol or isopropyl alcohol etc.; Described antiseptic is a sodium benzoate etc.
2, the preparation method of a kind of florfenicol liposome preparation according to claim 1, it is characterized in that the fluorine Buddhist nun is examined 2-6kg, sodium benzoate 40g puts into the beaker of 20L, add propylene glycol 2-15L, put beat in the colloid mill even after, add injection soybean oil 1-6kg, put again to beat in the colloid mill and spare, add soybean phospholipid 400-600g again, beat even with colloid mill, add injection water 0.5-1L, beat evenly with colloid mill repeatedly, add the injection water again to 40L, beat even with colloid mill, place the ATS high pressure homogenizer again, homogenizing repeatedly under 800-1200bar pressure, emulsion reaches below 10 nanometers, be finished product, it is 10% that the fluorine Buddhist nun examines content.
3, the preparation method of a kind of florfenicol liposome preparation according to claim 2, it is characterized in that florfenicol 4.0kg, sodium benzoate 40g puts into the beaker of 20L, adding propylene glycol 12L stirs evenly, put beat in the colloid mill even after, add injection soybean oil 4kg, put again to beat in the colloid mill and spare, add soybean phospholipid 600g again, beat even with colloid mill, add injection water 0.5-1L, beat evenly with colloid mill repeatedly, be settled to 40L, beat even with colloid mill with water for injection, place under the ATS high pressure homogenizer 800-1200bar pressure homogenizing repeatedly again, the breast grain reaches below 10 nanometers.
4, the preparation method of a kind of florfenicol liposome preparation according to claim 2, it is characterized in that florfenicol 2.0kg, sodium benzoate 40g puts into the beaker of 20L, adding propylene glycol 8L stirs evenly, put beat in the colloid mill even after, add injection soybean oil 6kg, put again to beat in the colloid mill and spare, add soybean phospholipid 400g again, beat even with colloid mill, add injection water 0.5-1L, beat evenly with colloid mill repeatedly, be settled to 40L, beat even with colloid mill with water for injection, place under the ATS high pressure homogenizer 800-1200bar pressure homogenizing repeatedly again, the breast grain reaches below 10 nanometers.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910013571A CN101653415A (en) | 2009-09-01 | 2009-09-01 | Florfenicol liposome preparation and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910013571A CN101653415A (en) | 2009-09-01 | 2009-09-01 | Florfenicol liposome preparation and preparation method thereof |
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| CN101653415A true CN101653415A (en) | 2010-02-24 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102283807A (en) * | 2010-06-18 | 2011-12-21 | 鲁翠涛 | Preparation method and application method of liquid precursor lipidosome |
| CN102688153A (en) * | 2012-06-05 | 2012-09-26 | 东南大学 | Blank liposome prepared by compounding phospholipid and preparation method thereof |
| CN102846550A (en) * | 2012-09-05 | 2013-01-02 | 郑州后羿制药有限公司 | Preparation method for florfenicol liposome |
| CN104161727A (en) * | 2013-08-30 | 2014-11-26 | 郑州后羿制药有限公司 | Adprin liposome and preparation method thereof |
| CN108210459A (en) * | 2016-12-13 | 2018-06-29 | 河南后羿实业集团有限公司 | A kind of carbasalate calcium Liposomal formulation and preparation method thereof |
-
2009
- 2009-09-01 CN CN200910013571A patent/CN101653415A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102283807A (en) * | 2010-06-18 | 2011-12-21 | 鲁翠涛 | Preparation method and application method of liquid precursor lipidosome |
| CN102688153A (en) * | 2012-06-05 | 2012-09-26 | 东南大学 | Blank liposome prepared by compounding phospholipid and preparation method thereof |
| CN102846550A (en) * | 2012-09-05 | 2013-01-02 | 郑州后羿制药有限公司 | Preparation method for florfenicol liposome |
| CN102846550B (en) * | 2012-09-05 | 2014-06-11 | 郑州后羿制药有限公司 | Preparation method for florfenicol liposome |
| CN104161727A (en) * | 2013-08-30 | 2014-11-26 | 郑州后羿制药有限公司 | Adprin liposome and preparation method thereof |
| CN104161727B (en) * | 2013-08-30 | 2016-08-10 | 郑州后羿制药有限公司 | A kind of A De furan woods liposome and preparation method thereof |
| CN108210459A (en) * | 2016-12-13 | 2018-06-29 | 河南后羿实业集团有限公司 | A kind of carbasalate calcium Liposomal formulation and preparation method thereof |
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Open date: 20100224 |