CN105597082B - A kind of cow breast injectant and preparation method thereof containing antibacterial peptide - Google Patents
A kind of cow breast injectant and preparation method thereof containing antibacterial peptide Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0041—Mammary glands, e.g. breasts, udder; Intramammary administration
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Abstract
The invention belongs to veterinary drug class technical fields, more particularly to one kind by injection stage Lincomycin Hydrochloride, nisin forms the cow breast injectant and preparation method thereof containing antibacterial peptide, the composition of raw material needed for the every 70.0g of cow breast injectant containing antibacterial peptide is as follows: injection stage Lincomycin Hydrochloride 4.0-4.5g, ten thousand unit of nisin 200-350, stearine 4.5-5.5g, wetting agent 0.7-1.0g, oil for injection 48.9-55.0g, the present invention overcomes existing breast injection narrow antimicrobial spectrums, the undesirable problem of clinical effectiveness, mastitis for milk cows caused by various pathogenic bacteria can effectively be treated, clinical effectiveness is obvious, short treating period, it effectively shortens and abandons the milk phase, reduce mastitis for milk cows bring economic loss, preparation method is simple to operation , it is suitable for being mass produced.
Description
Technical field
The invention belongs to veterinary drug class fields, and in particular to one kind is by injection stage Lincomycin Hydrochloride, nisin group
At the cow breast injectant and preparation method thereof containing antibacterial peptide.
Background technique
Recently as the continuous adjustment of cultivation structure, the milk cow production in China has obtained tremendous development in scale,
However the disease incidence of mastitis for milk cows in production is very high, there is this disease in the area of all breeding milk cows.Mammitis be by
Streptococcus, Escherichia coli, indoles peptococcus, melanocyte bacteroid, produces gemma fusiform Bacillus and gangrene at staphylococcus aureus
One kind caused by the pathogens such as Fusobacterium is multiple, stubborn disease.
According to statistics, clinic mastitis accounts for 21%~23% that milk cow always falls ill.Because Milk Production declines caused by it, the area Bing Ru
Discarded, the serious person of milk, newborn area's suppuration, gangrene, atrophy etc. cause permanently to lose ability and lose its value, therefore and
Superseded milk cow Zhan it is always superseded 40%~60%.Foreign study reports mastitis for milk cows disease incidence 20%~70%, and China reports
Disease incidence 40%~80%.
Because economic loss caused by mastitis for milk cows is huge, although China is reported without special economic loss
With exact data statistics, it is contemplated that every year because caused by mammitis economic loss also at as many as 7~800,000,000 yuan.This disease is not only given
Aquaculture causes great economic loss, and seriously endangers human health.Therefore, seem to the prevention and treatment of mastitis for milk cows
It is particularly important.
Patent application CN104382923A(201410583496.X) disclose a kind of milk cow Lincomycin Hydrochloride breast
Injectant and preparation method thereof, the patented product are single preparations of ephedrine, do not compound effective component.Because Lincomycin Hydrochloride belong to it is narrow
Antibiotic is composed, is had compared with high antibacterial activity, together to gram positive bacteria such as staphylococcus (including penicillin resistant strain), streptococcus etc.
When also have good antibacterial activity to Grain-negative anaerobic bacteria.But to Escherichia coli, production gemma fusiform Bacillus and gangrenous shuttle bar
Microbial mastitis for milk cows does not have effect.CN104382898A(201410565908., 7) a kind of amoxicillin is disclosed
Breast injection and preparation method thereof, although which has compounded synergistic component, but active constituent is all antibiotic.The drug pair
Most of pathogenic G+ bacterium and G- bacterium (including coccus and bacillus) have powerful antibacterial and bactericidal effect, but to cow breast
But there is serious drug resistance in the staphylococcus of one of scorching main pathogenic bacteria.
Summary of the invention
One kind is provided it is an object of the invention to overcome the deficiencies in the prior art with Lincomycin Hydrochloride and cream
The cow breast injectant containing antibacterial peptide and preparation method thereof of acid streptococci peptide composition, for treating Lactation of Dairy Cow phase breast
It is scorching.Product of the present invention cooperates with medication with antibiotic using antibacterial peptide, can effectively treat cow breast caused by various pathogenic bacteria
Inflammation reduces the dosage of antibiotic, shortens the clinical application time on the basis of improving product clinical effectiveness；And then effectively
The abandoning milk time generated by mammitis is shortened, the economic loss because of caused by the disease is effectively reduced.
The object of the present invention is achieved like this:
A kind of cow breast injectant containing antibacterial peptide, it is characterised in that: the cow breast injectant containing antibacterial peptide
The composition of raw material needed for every 70.0g is as follows: injection stage Lincomycin Hydrochloride 4.0-4.5g, nisin 200-350 ten thousand are single
Position, stearine 4.5-5.5g, wetting agent 0.7-1.0g, oil for injection 48.9-55.0g.
A kind of composition of raw material needed for the every 70.0g of cow breast injectant containing antibacterial peptide is as follows: injecting grade hydrochloric acid woods
Can mycin 4.0g, 2,000,000 unit of nisin, stearine 4.5g, wetting agent 0.7g, 55.0 g of oil for injection.
The wetting agent is one of Tween-80, soybean lecithin, Arlacel-80.
The oil for injection is one of injection soybean oil, atoleine, rilanit special.
A kind of cow breast injectant preparation method containing antibacterial peptide, which is characterized in that preparation method is as follows:
Step 1), take oil for injection total amount 20%-25% oil for injection, the injection grade hydrochloric acid woods that above-mentioned deal is added can
Mycin, nisin and wetting agent, stir evenly, and grind in colloid grinding tool, make drug granule partial size 15 microns with
Under, asNumber solution for standby；
The glyceryl stearate of recipe quantity is added in the oil for injection of step 2, the another 40%-50% for taking oil for injection total amount, heating
Acid esters stirs to dissolve, and lets cool conductSolution for standby；
Step 3), generalSolution andSolution mixing, after mixing evenly, is added remaining oil for injection, emulsifies, and packing is gone out
Bacterium.
Grinding condition in the step 1) are as follows: adjusting abrasive disk space makes abrasive disk space between 10-12 microns, grinds
Time is 15-20 minutes.
Heating condition in the step 2) are as follows: 100-110 DEG C heating 15-20 minutes；The temperature that lets cool is 50-
60℃。
Emulsifying temperature in the step 3) are as follows: 40-50 DEG C, emulsification times 20-30 minutes, mulser output speed was
10000rpm；Sterilization method is -60 irradiation sterilization of cobalt.
Lincomycin Hydrochloride effect is similar to erythromycin, to gram positive bacteria such as staphylococcus (including penicillin resistant
Strain), streptococcus etc. has compared with high antibacterial activity, while also having good antibacterial activity to Grain-negative anaerobic bacteria.Its mechanism of action
It is similar with erythromycin, belong to bacteriostatic agent.The main synthesis for inhibiting bacterial cellular protein matter.
Nisin (NISIN) is also known as streptococcus lactis peptide, is a kind of peptide material that certain streptococcus lactis generate, by
34 amino acid residue compositions can be degraded to amino acid by the intracorporal enzyme of people and be absorbed by alimentary canal, be a kind of efficient, safety, nothing
Natural antiseptic agent malicious, without side-effects.It can inhibit most gram-positive bacterias, especially to the gram-positive bacteria for generating gemma
Such as bacillus subtilis, bacillus stearothermophilus have very strong inhibiting effect, also can inhibit some gram-negative bacterias, such as husky
The growth of door Salmonella, Escherichia coli, pseudomonad etc., the main pathogenic bacteria including mastitis for milk cows.
The invention has the following advantages that
1) present invention is a kind of compound preparation being made of Lincomycin Hydrochloride, nisin, overcomes existing cream
Room injectant narrow antimicrobial spectrum, the undesirable problem of clinical effectiveness.Mastitis for milk cows caused by various pathogenic bacteria can be effectively treated,
Clinical effectiveness is obvious, short treating period, effectively shortens and abandons the milk phase, reduces mastitis for milk cows bring economic loss.
2) preparation method of the invention is simple to operation, is suitable for being mass produced.
Specific embodiment
Embodiment 1: a kind of its supplementary material ingredient of the cow breast injectant containing antibacterial peptide is as follows:
Active constituent: injection stage Lincomycin Hydrochloride 4.0g
2,000,000 unit of nisin
Excipient: stearine 4.5g
Arlacel-80 0.7g
Injection soybean oil 55.0g
Preparation method:
1) injection stage Lincomycin Hydrochloride, nisin and the profit of above-mentioned deal is added in the oil for injection for, taking 20%
Humectant stirs evenly, and grinds in colloid grinding tool, and adjusting abrasive disk space makes abrasive disk space between 10-12 microns, milling time
It is 15-20 minutes.Make drug granule partial size at 15 microns hereinafter, conductNumber solution for standby；
2), separately 40% oil for injection is taken to be heated to 100-110 DEG C, the stearine of above-mentioned deal is added, stirred
It makes it dissolve within 15-20 minutes, lets cool to 50-60 DEG C, asSolution for standby；
3), willSolution andSolution mixing, after mixing evenly, is added the oil for injection of surplus, emulsifies, emulsifying temperature
It is 40-50 DEG C, emulsification times 20-30 minutes, mulser output speed was 10000rpm packing, -60 irradiation sterilization of cobalt.
Embodiment 2: a kind of its supplementary material ingredient of the cow breast injectant containing antibacterial peptide is as follows:
Active constituent: injection stage Lincomycin Hydrochloride 4.0g
3,500,000 unit of nisin
Excipient: stearine 4.5g
Arlacel-80 0.7g
Injection soybean oil 50.7g
Preparation method: with embodiment 1
Embodiment 3: a kind of its supplementary material ingredient of the cow breast injectant containing antibacterial peptide is as follows:
Active constituent: injection stage Lincomycin Hydrochloride 4.0g
2,000,000 unit of nisin
Excipient: stearine 5.5g
Arlacel-80 0.7g
Injection soybean oil 54.0g
Preparation method: with embodiment 1
Embodiment 4: a kind of its supplementary material ingredient of the cow breast injectant containing antibacterial peptide is as follows:
Active constituent: injection stage Lincomycin Hydrochloride 4.0g
2,000,000 unit of nisin
Excipient: stearine 4.5g
Arlacel-80 1.0g
Injection soybean oil 54.7g
Preparation method: with embodiment 1
Embodiment 5: a kind of its supplementary material ingredient of the cow breast injectant containing antibacterial peptide is as follows:
Active constituent: injection stage Lincomycin Hydrochloride 4.5g
3,500,000 unit of nisin
Excipient: stearine 5.5g
Arlacel-80 1.0g
Injection soybean oil 48.9g
Preparation method: with embodiment 1
Embodiment 6: a kind of its supplementary material ingredient of the cow breast injectant containing antibacterial peptide is as follows:
Active constituent: injection stage Lincomycin Hydrochloride 4.5g
2,000,000 unit of nisin
Excipient: stearine 5.5g
Arlacel-80 1.0g
Injection soybean oil 53.2g
Preparation method: with embodiment 1
Embodiment 7: a kind of its supplementary material ingredient of the cow breast injectant containing antibacterial peptide is as follows:
Active constituent: injection stage Lincomycin Hydrochloride 4.5g
3,500,000 unit of nisin
Excipient: stearine 4.5g
Arlacel-80 1.0g
Injection soybean oil 49.9g
Embodiment 8: a kind of its supplementary material ingredient of the cow breast injectant containing antibacterial peptide is as follows:
Active constituent: injection stage Lincomycin Hydrochloride 4.5g
3,500,000 unit of nisin
Excipient: stearine 5.5g
Arlacel-80 0.7g
Injection soybean oil 49.2g
Clinical pharrnacokinetics test of the present invention in treatment mastitis for milk cows disease:
One, case:
Harbin City, cattle farm, suburb is determined as milk cow 86 of lactation period clinic mastitis after diagnosing.
Two, trial drug:
1) product of the present invention Lincomycin Hydrochloride breast injection (lactation period), content specification are 7.0g:350mg.2) city
Certain the company's Lincomycin Hydrochloride breast injection (lactation period) sold, content specification are 7.0g:350mg.
Three, test method:
The ox that suffers from for being diagnosed as mammitis is randomly divided into experimental group and control group, experimental group 43, control group 43.Experiment
The treatment method that group milk cow uses is the breast injection for taking the embodiment of the present invention 1, each cream Qu Yizhi after milking, one day two
It is secondary, it is used in conjunction 2 times；Control group: using commercially available Lincomycin Hydrochloride breast injection, each cream Qu Yizhi after milking, one day two
It is secondary, it is used in conjunction 2 times.
Before administration and the 7th day after last time administration, the milk sample 20mL progress that newborn area is administered in each test group is acquired respectively
Bacteriology checking and milk somatic cell measurement.Investigate breast local clinical symptom, milking capacity and the milk before and after milk cow medication
Character, overall merit contain curative effect of the Lincomycin Hydrochloride breast injection to mastitis for milk cows of antibacterial peptide.
Four, experiment conclusion:
1) detection of pathogens is the result shows that Lincomycin Hydrochloride breast is perfused in (being shown in Table 1), the infection cream area of mammitis milk cow
Injectant (lactation period), after each 1 time, continuous use 2 times early daily, late, bacterium is low from 24 plants before administration in experimental group cow's milk
3 plants after to administration；Bacterium is reduced to 14 plants after administration from 25 plants before administration respectively in control group cow's milk.Illustrate the present invention
Drug is better than scavenging effect of the control drug to main pathogen of bovine mastitis.
Table 1: the separation qualification result statistics of the main pathogenic fungi before and after the medication of each test group milk cow's milk area
2) milk cow somatic number is the result shows that (see Table 2), and milk SCC is lower than 2 × 10 in experimental therapy group5The cream of a/mL
Ratio shared by area is 93.0%；And ratio shared by randomized controlled treatment group only has 72.1%.
Table 2: high somatic number result statistics in milk before and after the medication of each test group milk cow's milk area
3) the breast local clinical symptom before and after milk cow medication, milking capacity and milk character, comprehensive evaluation result show
(see Table 4), the cure rate of mastitis for milk cows reaches 93.0% in experimental group, and the cure rate in control group is only up to 69.7%.
Invention formulation product clinical effectiveness is substantially better than commercially available said preparation product.
Table 3: Clinical evaluation standard before and after the medication of each test group milk cow's milk area
Table 4: clinical effectiveness comprehensive evaluation result before and after the medication of each test group milk cow's milk area
Claims (5)
1. a kind of cow breast injectant containing antibacterial peptide, it is characterised in that: the cow breast injectant containing antibacterial peptide is every
The composition of raw material needed for 70.0g is as follows: injection stage ten thousand unit of Lincomycin Hydrochloride 4.0-4.5g, nisin 200-350,
Stearine 4.5-5.5g, wetting agent 0.7-1.0g, oil for injection 48.9-55.0g.
2. the cow breast injectant according to claim 1 containing antibacterial peptide, it is characterised in that: one kind contains antibacterial peptide
The every 70.0g of cow breast injectant needed for raw material composition it is as follows: injection stage Lincomycin Hydrochloride 4.0g, nisin
2000000 units, stearine 4.5g, wetting agent 0.7g, oil for injection 55.0g.
3. the cow breast injectant according to claim 1 containing antibacterial peptide, it is characterised in that: the wetting agent is
One of Tween-80, soybean lecithin, Arlacel-80.
4. the cow breast injectant according to claim 1 containing antibacterial peptide, it is characterised in that: the oil for injection
For one of injection soybean oil, atoleine, rilanit special.
5. a kind of cow breast injectant preparation method containing antibacterial peptide, it is characterised in that: its preparation step is as follows:
Step 1), take oil for injection 48.9-55.0g total amount 20%-25% oil for injection, be added injection grade hydrochloric acid woods can be mould
Plain 4.0-4.5g, ten thousand unit of nisin 200-350 and wetting agent 0.7-1.0g, stir evenly, grind in colloid grinding tool
Mill, makes drug granule partial size at 15 microns hereinafter, as I solution for standby；
The glycerol stearate of recipe quantity is added in the oil for injection of step 2), the another 40%-50% for taking oil for injection total amount, heating
Ester 4.5-5.5g, stirs to dissolve, and lets cool as II solution for standby；
Step 3) mixes I solution and II solution, after mixing evenly, remaining oil for injection is added, emulsifies, dispenses, sterilizing；
Wherein, the grinding condition in step 1) are as follows: adjusting abrasive disk space makes abrasive disk space between 10-12 microns, milling time
Be 15-20 minutes, heating condition in step 2) are as follows: 100-110 DEG C heating 15-20 minutes, the described temperature that lets cool is 50-60
DEG C, emulsifying temperature in step 3) are as follows: 40-50 DEG C, emulsification times 20-30 minutes, mulser output speed was 10000rpm, sterilizing
Mode is -60 irradiation sterilization of cobalt.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102068684A (en) * | 2011-01-21 | 2011-05-25 | 河南亚卫动物药业有限公司 | Perfusate and preparation method thereof for treating cow recessive mastitis |
| CN102114175A (en) * | 2009-12-31 | 2011-07-06 | 天津瑞普生物技术股份有限公司 | Compound preparation for treating acute mastitis of milk cow |
| CN103520702A (en) * | 2013-10-15 | 2014-01-22 | 安泰生物工程股份有限公司 | Cow udder cleaning agent used for preventing bovine mastitis |
| 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 |
| CN104606218A (en) * | 2015-01-08 | 2015-05-13 | 邳州正康生物技术有限公司 | Breast injection for treating cow lactation mastitis and preparation method thereof |
-
2016
- 2016-01-29 CN CN201610062708.9A patent/CN105597082B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102114175A (en) * | 2009-12-31 | 2011-07-06 | 天津瑞普生物技术股份有限公司 | Compound preparation for treating acute mastitis of milk cow |
| CN102068684A (en) * | 2011-01-21 | 2011-05-25 | 河南亚卫动物药业有限公司 | Perfusate and preparation method thereof for treating cow recessive mastitis |
| CN103520702A (en) * | 2013-10-15 | 2014-01-22 | 安泰生物工程股份有限公司 | Cow udder cleaning agent used for preventing bovine mastitis |
| 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 |
| CN104606218A (en) * | 2015-01-08 | 2015-05-13 | 邳州正康生物技术有限公司 | Breast injection for treating cow lactation mastitis and preparation method thereof |
Non-Patent Citations (1)
| Title |
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| 奶牛乳房炎综合防控关键技术研究进展;刘龙海等;《中国草食动物科学》;20151231;第35卷(第5期);第56-61页 |
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