CN103230365A - Novel slow-release breast perfusion agent for preventing cow subclinical mastitis in milk shortage stage - Google Patents
Novel slow-release breast perfusion agent for preventing cow subclinical mastitis in milk shortage stage Download PDFInfo
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- CN103230365A CN103230365A CN2013100870679A CN201310087067A CN103230365A CN 103230365 A CN103230365 A CN 103230365A CN 2013100870679 A CN2013100870679 A CN 2013100870679A CN 201310087067 A CN201310087067 A CN 201310087067A CN 103230365 A CN103230365 A CN 103230365A
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Abstract
The invention provides a novel slow-release breast perfusion agent for preventing cow subclinical mastitis in a milk shortage stage. 100g of the novel slow-release breast perfusion agent comprises 7-11g of cefalonium, 0.5 to 8g of polyethylene glycol-400, Tween materials or propylene glycol, 0.5 to 8g of fatty alcohol polyoxyethylene ether, cyclomethylene glyceryl ether, triacetin or poloxamer, 0.5 to 8g of aluminum stearate or silica, 0.02 to 0.05g of vitamin E, 0.05 to 0.1g of benzyl alcohol, and the balance liquid paraffin, soybean oil for injection or median chain triglyceride. The invention also provides a preparation method of the novel slow-release breast perfusion agent. The novel slow-release breast perfusion agent is suspension colloid, can be slowly released, can effectively reduce administration frequency, can effectively prevent and treat cow subclinical mastitis by being used in a milk shortage stage, and does not produce residues. Compared with the like foreign products, the suspension colloid has better stability.
Description
Technical field
The present invention relates to the veterinary medicament preparation field, specifically, relate to a kind of slow release breast perfusion preparation that prevents the milk cow recessive mastitis and preparation method thereof.
Background technology
Bovine mastitis is one of common disease of harm milk cattle cultivating industry, and the whole world has 50% milch cow to suffer from various types of bovine mastitis approximately, and milk cattle cultivating is already caused enormous economic loss.The main cause that causes bovine mastitis is cause pathogeny imcrobe infection, and is wherein common with these 5 kinds of cause of disease types of staphylococcus aureus, streptococcus agalactiae, streptococcus dysgalactiae, streptococcus uberis and various gram negative bacteria especially.The milk cow recessive mastitis do not have tangible clinical symptoms, show as the milk somatic cell number and raise, and milk yield descends, and the composition of milk changes, thereby influences the quality of milk.Can develop into clinical type mastitis as untimely treatment or malpractice, even cause blind teat, cause milch cow to be eliminated when serious.Because problems such as sickness rate height and milk antibiotic remains are not generally treated subclinical mastitis.
Slow releasing preparation refers to reduce medicine and enter the absorption rate of body, thereby play better therapeutic effect by delaying the rate of release of medicine from this dosage form.
Summary of the invention
The purpose of this invention is to provide a kind of novel slow release breast perfusion preparation for prevention milk cow recessive mastitis in the dry milk phase.
The present invention also provides the preparation method of described filling agent.
In order to realize the object of the invention, contain cefalonium 7-11g in a kind of every 100g filling agent of slow release breast that prevents the milk cow recessive mastitis of the present invention, Polyethylene Glycol-400(PEG-400), Tweens material or propylene glycol 0.5-8g, fatty alcohol-polyoxyethylene ether (AEO-7) glycerol formal, glyceryl triacetate or poloxamer 0.5-8g, aluminium stearate or silicon dioxide 0.5-8g, vitamin E 0.02-0.05g, benzyl alcohol 0.05-0.1g, surplus is liquid paraffin, injection soybean oil or median chain triglyceride oil.
Preferably, described filling agent is grouped into by following one-tenth: contain cefalonium 9g in every 100g filling agent, and Polyethylene Glycol-4001g, fatty alcohol-polyoxyethylene ether 1g, aluminium stearate 2g, vitamin 0.04g, benzyl alcohol 0.06g, surplus is liquid paraffin.
The present invention also provides the preparation method of described filling agent, may further comprise the steps:
(1) the cefalonium crude drug is crushed to 90% above particle diameter and reaches 3-5 μ m, sterilization reaches aseptic requirement, is material A;
(2) with liquid paraffin sterilization (with aseptic membrane filtration degerming), add Polyethylene Glycol-400(PEG-400), fatty alcohol-polyoxyethylene ether (AEO-7) and aluminium stearate, stirring and evenly mixing continues to heat 4-6 hour, is down to room temperature, namely gets liquid B;
(3) material A, liquid B, vitamin E and benzyl alcohol are dosed in the high pressure homogenization machine, utilize the even matter 5-10min of high pressure homogenization machine circulation, pressure is controlled at 50-150MPa, quantitatively to prescribed dose, and packing, sealing, packing.
It is of the present invention that slow release breast perfusion preparation for prevention milk cow recessive mastitis can also use as eye ointment or uterus filling agent in the dry milk phase.
Of the present invention is the suspendible colloid in the dry milk phase for the slow release breast perfusion preparation that prevents the milk cow recessive mastitis, can slowly discharge, reduce administration number of times effectively, use this filling agent in the administration of dry milk phase, can effectively prevent the generation of milk cow recessive mastitis, characteristics with noresidue in milk lactation period are compared with external like product, and the suspendible colloid of this dosage form has better stability.
Description of drawings
Fig. 1 is the release in vitro of the cefalonium filling agent of preparation in the embodiment of the invention 1 line curve of writing music.
The specific embodiment
Following examples are used for explanation the present invention, but are not used for limiting the scope of the invention.If do not specialize the conventional means that used technological means is well known to those skilled in the art among the embodiment, the raw materials used commercial goods that is.
Embodiment 1 is used for slow release breast perfusion preparation and the preparation thereof of prevention milk cow recessive mastitis in the dry milk phase
The composition of every 100g filling agent is composed as follows:
The cefalonium crude drug is crushed to 90% above particle diameter reaches 3-5 μ m, sterilization reaches aseptic requirement, is material A; With liquid paraffin sterilization (with aseptic membrane filtration degerming), add Polyethylene Glycol-400(PEG-400), fatty alcohol-polyoxyethylene ether (AEO-7) and aluminium stearate, stirring and evenly mixing continues to heat 5 hours, is down to room temperature, is liquid B; Material A, liquid B, vitamin E, benzyl alcohol are dosed to the high pressure homogenization machine, utilize the even matter 7min of high pressure homogenization machine circulation, pressure is controlled at 50MPa, quantitatively to 100g, and packing, sealing, packing.
Embodiment 2 is used for slow release breast perfusion preparation and the preparation thereof of prevention milk cow recessive mastitis in the dry milk phase
The composition of every 100g filling agent is composed as follows:
The cefalonium crude drug is crushed to 95% above particle diameter reaches 3-5 μ m, sterilization reaches aseptic requirement, is material A; With liquid paraffin sterilization (with aseptic membrane filtration degerming), add Polyethylene Glycol-400(PEG-400), fatty alcohol-polyoxyethylene ether (AEO-7) and aluminium stearate, stirring and evenly mixing continues to heat 4 hours, is down to room temperature, is liquid B; Material A, liquid B, vitamin E, benzyl alcohol are dosed to the high pressure homogenization machine, utilize the even matter 5min of high pressure homogenization machine circulation, pressure is controlled at 150MPa, quantitatively to 100g, and packing, sealing, packing.
Embodiment 3 is used for slow release breast perfusion preparation and the preparation thereof of prevention milk cow recessive mastitis in the dry milk phase
The composition of every 100g filling agent is composed as follows:
The cefalonium crude drug is crushed to 90% above particle diameter reaches 3-5 μ m, sterilization reaches aseptic requirement, is material A; With injection soybean oil sterilization (with aseptic membrane filtration degerming), add tween 80, glycerol formal and aluminium stearate, stirring and evenly mixing continues heating 5 hours, is down to room temperature, is liquid B; Material A, liquid B, vitamin E, benzyl alcohol are dosed to the high pressure homogenization machine, utilize the even matter 9min of high pressure homogenization machine circulation, pressure is controlled at 120MPa, quantitatively to 100g, and packing, sealing, packing.
Embodiment 4 is used for slow release breast perfusion preparation and the preparation thereof of prevention milk cow recessive mastitis in the dry milk phase
The composition of every 100g filling agent is composed as follows:
The cefalonium crude drug is crushed to 95% above particle diameter reaches 3-5 μ m, sterilization reaches aseptic requirement, is material A; With median chain triglyceride oil sterilization (with aseptic membrane filtration degerming), add Tween-60, glyceryl triacetate and silicon dioxide, stirring and evenly mixing continues heating 6 hours, is down to room temperature, is liquid B; Material A, liquid B, vitamin E, benzyl alcohol are dosed to the high pressure homogenization machine, utilize the even matter 10min of high pressure homogenization machine circulation, pressure is controlled at 120MPa, quantitatively to 100g, and packing, sealing, packing.
Embodiment 5 is used for slow release breast perfusion preparation and the preparation thereof of prevention milk cow recessive mastitis in the dry milk phase
The composition of every 100g filling agent is composed as follows:
The cefalonium crude drug is crushed to 90% above particle diameter reaches 3-5 μ m, sterilization reaches aseptic requirement, is material A; With injection soybean oil sterilization (with aseptic membrane filtration degerming), add propylene glycol, poloxamer and silicon dioxide, stirring and evenly mixing continues heating 4.5 hours, is down to room temperature, is liquid B; Material A, liquid B, vitamin E, benzyl alcohol are dosed to the high pressure homogenization machine, utilize the even matter 6min of high pressure homogenization machine circulation, pressure is controlled at 100MPa, quantitatively to 100g, and packing, sealing, packing.
Embodiment 6 is used for the application of the slow release breast perfusion preparation of prevention milk cow recessive mastitis in the dry milk phase
Use the slow release breast perfusion preparation for prevention milk cow recessive mastitis in the dry milk phase for preparing among the embodiment 1-5,134 2 years old milch cows of certain farm picked at random are carried out the treatment of dry milk phase, treat immediately after just finishing lactation period, its treatment can not be interrupted in the whole dry milk phase.Each nipple perfusion administration 3g of every cow head.In order to assess the effect of whole control process, before begin treatment, behind the begin treatment 2.5 months, 5 months, 7.5 months and differentiated the incidence rate of milk cow recessive mastitis in 10 months respectively.Preventive effect is assessed with the reduction rate of milk cow recessive mastitis.
The reduction rate of milk cow recessive mastitis=(A-B)/A * 100%
A: the incidence rate of the milk cow recessive mastitis before the treatment beginning; B: the incidence rate of milk cow recessive mastitis when treatment finishes.
The result is as shown in table 1.
The reduction rate of milk cow recessive mastitis before and after the treatment of table 1 dry milk phase
Annotate: the milk ox head number of subclinical mastitis for taking place in I, and II is the incidence rate of milk cow recessive mastitis
What prepare among the embodiment 1-5 as can be seen from Table 1, is used for preventing the slow release breast perfusion preparation of milk cow recessive mastitis that bovine mastitis is had the good preventing therapeutical effect in the dry milk phase.
The release in vitro of the embodiment 7 filling agents of the present invention line of writing music
Accurately extract the cefalonium filling agent 10ml of the embodiment 1 of mixing with syringe, putting into diameter is 1cm, be about in the bag filter of 20cm, remove a bag interior air, tighten with cotton rope at two, coiling is fixed on the digestion instrument stirring paddle, phosphate buffer 900ml with pH value 7.8 is dissolution medium, add low quantity of surfactant, keep temperature (37 ± 0.5) ℃, rotating speed is 100rpm, respectively at 0.5h, 1h, 2h, 4h, 8h, 12h, 16h, 20h, 24h and 48h sampling 5ml, and in time replenish dissolution medium 5ml, utilize the release amount of medicine of high-performance liquid chromatogram determination day part, release in vitro is write music line as shown in Figure 1, illustrates that this dosage form has the good in vitro releasing effect.
Embodiment 8 drug residues detect (TTC method)
Drug residue detects and carries out according to TTC method operation sequence.The TTC ratio juris is: if when having antibiotic to exist in the milk, inoculated streptococcus thermophilus (Streptococcus thermophilus) after, the growth of antibacterial is suppressed, milk can not molding; If antibiotic-free exists in the milk, bacterial multiplication then makes the milk molding.Gather the back 49 days milk sample for the treatment of, drawing 10ml is put in the sterilized test tube, then test tube is placed on heating in water bath on the electric furnace, when reaching 80 ℃, take out test tube after keeping 5min, be placed on and be cooled to 37 ℃ in the cold water, in each test tube, add streptococcus thermophilus strain 2.5ml, be placed on behind the mixing in 37 ℃ the incubator and cultivated observed result 2.5 hours.
Drug residue free in the milk sample that drug withdrawal detected later in 49 days can continue with milk.The dry milk phase of milch cow was generally about 60 days, did not produce drug residue in lactation period so can not cause in the treatment of dry milk phase.
Adopt the dry milk phase Therapeutic Method identical with embodiment 6 in the present embodiment.The medicine that uses is the slow release breast perfusion preparation of the prevention milk cow recessive mastitis that prepare among the embodiment 1-5.
Embodiment 9 investigates the stability of filling agent of the present invention
Cefalonium filling agent and the external like product of preparation among the embodiment 1 are placed the close plug of 100ml tool plug graduated cylinder respectively, jolting is 1 minute separately, record settling volume that two kinds of dosage forms place 3 days, 7 days, 14 days, 21 days, 28 days and 35 days respectively than (table 2), computing formula:
Settling volume compares F=H
u/ H
0
Wherein, H
0Be the elemental height of suspension, H
uBe the precipitum height.
Table 2 settling volume compares experimental result
| ? | The cefalonium filling agent | External like product |
| 3 days | 0.99 | 0.98 |
| 7 days | 0.98 | 0.95 |
| 14 days | 0.97 | 0.68 |
| 21 days | 0.95 | 0.49 |
| 28 days | 0.92 | 0.33 |
| 35 days | 0.87 | 0.18 |
Cefalonium filling agent and the external like product of preparation among the embodiment 1 are rotated 5min respectively under the 2000rpm rotating speed, make its precipitation, then tool plug graduated cylinder is inverted upset (anti-just for once), is recorded precipitum at the bottom of the tube is disperseed required upset number of times (table 3) again.
Table 3 is the dispersion experiment result again
| ? | The cefalonium filling agent | External like product |
| Be inverted the upset number of times | 2 | 5 |
Settling volume than and again the dispersion experiment result proved effectively and utilize the stability of the cefalonium filling agent form formula that high pressure homogenization mechanism is equipped with obviously to be better than external like product that good stable is conducive to preservation and the transportation of preparation.
Though above the present invention is described in detail with a general description of the specific embodiments, on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements all belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (3)
1. slow release breast perfusion preparation that is used for prevention milk cow recessive mastitis in the dry milk phase, it is characterized in that, be grouped into by following one-tenth: contain cefalonium 7-11g in every 100g filling agent, Polyethylene Glycol-400, Tweens material or propylene glycol 0.5-8g, fatty alcohol-polyoxyethylene ether, glycerol formal, glyceryl triacetate or poloxamer 0.5-8g, aluminium stearate or silicon dioxide 0.5-8g, vitamin E 0.02-0.05g, benzyl alcohol 0.05-0.1g, surplus is liquid paraffin, injection soybean oil or median chain triglyceride oil.
2. filling agent according to claim 1 is characterized in that, contains cefalonium 9g in every 100g filling agent, Polyethylene Glycol-4001g, and fatty alcohol-polyoxyethylene ether 1g, aluminium stearate 2g, vitamin 0.04g, benzyl alcohol 0.06g, surplus is liquid paraffin.
3. the preparation method of the described filling agent of claim 2 is characterized in that, may further comprise the steps:
1) particle diameter that the cefalonium crude drug is crushed to more than 90% reaches 3-5 μ m, and sterilization is material A;
2) add Polyethylene Glycol-400, fatty alcohol-polyoxyethylene ether and aluminium stearate in liquid paraffin, stirring and evenly mixing continues heating 4-6 hour, is down to room temperature, namely gets liquid B;
3) material A, liquid B, vitamin E and benzyl alcohol are dosed in the high pressure homogenization machine, pressure is 50-150Mpa, even matter 5-10min.
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| CN201310087067.9A CN103230365B (en) | 2013-03-19 | 2013-03-19 | Novel slow-release breast perfusion agent for preventing cow subclinical mastitis in milk shortage stage |
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| CN103230365B CN103230365B (en) | 2014-12-03 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103479574A (en) * | 2013-09-12 | 2014-01-01 | 华南农业大学 | Breast injectant used for preventing and treating dry-milk-period dairy cow mastitis and preparation method thereof |
| CN104288136A (en) * | 2014-04-30 | 2015-01-21 | 郑州百瑞动物药业有限公司 | Chlorhexidine acetate uterus injectant for dairy cow, and preparation method thereof |
| CN105726461A (en) * | 2014-12-10 | 2016-07-06 | 瑞普（天津）生物药业有限公司 | Ceftiofur hydrochloride breast injectant during dry period |
| CN106074384A (en) * | 2016-08-08 | 2016-11-09 | 甘肃新天马制药股份有限公司 | A kind of pirlimycin micellar preparation and preparation method thereof |
| CN114404365A (en) * | 2022-01-18 | 2022-04-29 | 山东鲁抗舍里乐药业有限公司 | Cefalonium breast injection and preparation method and application thereof |
| CN115138444A (en) * | 2022-05-31 | 2022-10-04 | 青岛农业大学 | Preparation method and application of cefalonium cream for dairy cows |
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| CN101107015A (en) * | 2005-01-19 | 2008-01-16 | 日本全药工业株式会社 | Injection for mastitis |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103479574A (en) * | 2013-09-12 | 2014-01-01 | 华南农业大学 | Breast injectant used for preventing and treating dry-milk-period dairy cow mastitis and preparation method thereof |
| CN104288136A (en) * | 2014-04-30 | 2015-01-21 | 郑州百瑞动物药业有限公司 | Chlorhexidine acetate uterus injectant for dairy cow, and preparation method thereof |
| CN104288136B (en) * | 2014-04-30 | 2017-06-23 | 郑州百瑞动物药业有限公司 | A kind of milk cow chlorhexidine acetate uterus injectant and preparation method thereof |
| CN105726461A (en) * | 2014-12-10 | 2016-07-06 | 瑞普（天津）生物药业有限公司 | Ceftiofur hydrochloride breast injectant during dry period |
| CN106074384A (en) * | 2016-08-08 | 2016-11-09 | 甘肃新天马制药股份有限公司 | A kind of pirlimycin micellar preparation and preparation method thereof |
| CN114404365A (en) * | 2022-01-18 | 2022-04-29 | 山东鲁抗舍里乐药业有限公司 | Cefalonium breast injection and preparation method and application thereof |
| CN114404365B (en) * | 2022-01-18 | 2023-03-14 | 山东鲁抗舍里乐药业有限公司 | Cefalonium breast injection and preparation method and application thereof |
| CN115138444A (en) * | 2022-05-31 | 2022-10-04 | 青岛农业大学 | Preparation method and application of cefalonium cream for dairy cows |
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