CN103054833A - A formula of an antimicrobial oil emulsion microcapsule for veterinary use - Google Patents
A formula of an antimicrobial oil emulsion microcapsule for veterinary use Download PDFInfo
- Publication number
- CN103054833A CN103054833A CN2012105815813A CN201210581581A CN103054833A CN 103054833 A CN103054833 A CN 103054833A CN 2012105815813 A CN2012105815813 A CN 2012105815813A CN 201210581581 A CN201210581581 A CN 201210581581A CN 103054833 A CN103054833 A CN 103054833A
- Authority
- CN
- China
- Prior art keywords
- oil emulsion
- injection
- oil
- microcapsule
- antibacterials
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a formula of an antimicrobial oil emulsion microcapsule for veterinary use, wherein per 1000g of the antimicrobial oil emulsion microcapsule contains 50-100g of an antimicrobial agent, 250-500ml of oil for injection, 250-500ml of water for injection, 1-5g of PEG, 5-10ml of sorbitan fatty acid ester, 5-10ml of polyoxyethylene sorbitan fatty acid ester, 250-500g of soluble starch, and 50-100g of methyl cellulose. According to the present invention, the oil emulsion is developed to be microcapsules which can be used for oral administration, thereby maintaining the long-acting and sustained-release effects of the oil emulsion, while in a large extent preventing disadvantages and side reactions in the production and application of the oil emulsion. The preparation process of the microcapsules is relatively simple, reducing the use of organic solvents and thereby reducing the cost of the product.
Description
Technical field
The present invention relates to a kind of initiative of veterinary antibacterial novel form, relate in particular to veterinary antibacterial oil emulsion microcapsule coating agent, but make the administration of oily antibacterials Emulsion oral administration, thereby form durative action preparation oral administration new way, the invention still further relates to preparation method and the clinical practice of this dosage form.
Background technology
Current, in the Zoopharmacy field, particularly the dosage form generally used of antimicrobial drug galenic pharmacy field is several regular dosage forms such as pulvis, pre-mixing agent, light water needle injection, tablet and granule, and this type of preparation is being brought into play important function aspect the control Animal diseases.Yet animal husbandry disease all over the world constantly spreads in recent years, and has presented the vicious cycle trend of mixed infection, and the conventional pharmaceutical dosage form particularly regular dosage form in the antibacterials field is difficult to reach the purpose of current treatment bacterial infection disease.In recent years, the veterinary drug worker has carried out a large amount of research for novel formulation such as long-acting slow-release, targeting, the most outstanding is durative action preparation and targeting preparation, although such preparation can be to a certain extent should with some feature of veterinary drug medicine, such as long-acting medication number of times minimizing, targeting accurate positioning etc., but because oil emulsion can only administrated by injection, and the oil emulsion coefficient of viscosity is large, thereby clinical application is inconvenient.In addition, because the oil emulsion long-acting slow-release, exist in the injection site long period, larger to Animal stress, and might affect and butcher meat quality.Another kind of targeted drug is divided into the passive target of organ targeting and the active targeted drug with " navigation system ", the main dosage form of organ targeted drug is liposome, microcapsule etc., although analyze the effect that such passive organ targeted drug can produce targeted delivery of drugs to a great extent from test data, but this type of novel form is faced with simultaneously cost height, poor stability and must can reaches the good shortcomings such as drug effect by intravenous administration, this type of shortcoming has caused such novel formulation can't be in clinical practice, particularly in the antimicrobial drug field.Active targeted drug with " navigation system " can reach by other activated material modified antimicrobial medicines the purpose of accurate location, meanwhile, high cost, internal metabolism is too fast and the realistic problem that only can not solve the current animal husbandry development of China for minority antibacterial targeting fully.
For the light water needle injection, after intramuscular injection antibacterials distribute rapidly be diffused into blood circulation and on every side organize internal organs, thereby reach quick-acting effects.Since the most antimicrobial drugs of the metabolic characteristic of animal body in vivo the valid density time be generally 6～12h, such half-life makes the clinical application number of times increase to 2～3 times/days, has brought larger difficulty to practical operation.In recent years concentrate the exploitation long-acting slow-release preparation in order to change this present situation veterinary drug worker, long-acting oil emulsion is imperative.And oil emulsion administration operation is inconvenient and become the bottleneck that long-acting oil emulsion is applied at body local organization extended residual.How to get its advantage, abandon its drawback, make it conscientiously to meet the application of veterinary clinic antibacterials, become gradually study hotspot.
Summary of the invention
This invention is intended to use solid dispersions technique, oil emulsion is developed as the microcapsule coating agent of a class Orally-administrable, thereby when keeping the oil emulsion long-acting slow-release, largely avoided defective and the side reaction of oil emulsion in production application, because of preparation technology simpler, reduced the use of organic solvent, so greatly reduce product cost, for animal husbandry is providing corresponding technical support aspect Drug therapy and the health care.
Technical problem solved by the invention realizes by the following technical solutions:
A kind of prescription of veterinary antibacterial oil emulsion microcapsule coating agent is: this microcapsule coating agent of every 1000g contains antibacterials 50～100g, oil for injection 250～500mL, water for injection 250～500mL, PEG1～5g, sorbitan fatty acid ester 5～10mL, polyoxyethylene sorbitan fatty acid ester 5～10mL, soluble starch 250～500g, methylcellulose 50～100g, described veterinary antibacterial oil emulsion microcapsule coating agent comprises the veterinary antibacterial oil emulsion, and this oil emulsion is pulvis microcapsule granule state, and animal absorbs Emulsion when giving detoxification, antibacterials in the Emulsion in animal body substep discharge, and form slow release effect.
Wherein, described PEG can select from PEG5000-PEG8000, and described antibacterials are enrofloxacin, sulfanilamide hexakis-methoxy pyrimidine, doxycycline hydrochloride or florfenicol, also can be compound medicine.
Simultaneously, can in described antibacterials, add the effective ingredients in plant extract or the monomer that improve immunity of organisms, comprise astragalus polysaccharide extract, Radix Isatidis extract, Radix Et Rhizoma Rhei extract and berberine, Sanguinarine, bend Herba Gynurae bicoloris alkali plant monomer in vain.
Preferably, described oil for injection is injection soybean oil, injection Oleum Arachidis hypogaeae semen, injection Oleum Gossypii semen, injection Oleum Ricini or injection Oleum Camelliae.
Prepare above-mentioned any veterinary antibacterial oil emulsion microcapsule coating agent, include following preparation technology:
1) get oil for injection 250～500mL, sorbitan fatty acid ester 5～10mL is suspended in sorbitan fatty acid ester in the oil for injection, and is for subsequent use behind 121 ℃ of sterilization 30min;
2) get antibacterials 50～100g, polyoxyethylene sorbitan fatty acid ester 5～10mL is suspended in antibacterials and polyoxyethylene sorbitan fatty acid ester in the water for injection, and is for subsequent use behind 121 ℃ of sterilization 30min;
3) get above-mentioned two kinds of suspensions that prepare and mix, then emulsifying 30～60min prepares the water-in-oil type oil emulsion, and is for subsequent use behind 121 ℃ of sterilization 30min;
4) will be through described technique 3) after the oil emulsion made and soluble starch and the abundant stirring and evenly mixing of methylcellulose to microcapsule granule pulvis microcapsule granule state.
Wherein, antibacterials are present in the water of the described oil emulsion that microcapsule coats or oil, the water two-phase, according to different target animals the characteristics of pharmacokinetics of different antibacterials are adjusted accordingly.
Beneficial effect
1. the present invention organically combines the preparation technology of Emulsion and microcapsule coating agent, has changed the present situation that oil emulsion can only administrated by injection, and can the oral administration administration, forms a kind of new oral long-acting sustained-release agent.
2. the present invention uses that material is easy to get, the technique relative simple, cost is lower, the Emulsion syringeability is fabulous, is convenient to veterinary clinic and uses, and has a extensive future, and economic and social benefit is all obvious.
The specific embodiment
The present invention will be described in detail for example for the below.
Embodiment 1
The preparation of 20% florfenicol Emulsion microcapsule formulation, In Vitro Bacteriostasis effect and clinical practice
Prescription:
Florfenicol 80g
Oil for injection 300ml
Span-80 10ml
Tween-80 5ml
Water for injection 250ml
PEG8000 1.0g
Soluble starch 250g
Methylcellulose 50g
This oil emulsion microcapsule coating agent comprises the veterinary antibacterial oil emulsion, and this oil emulsion is pulvis microcapsule granule state, and animal absorbs Emulsion when giving detoxification, and the antibacterials in the Emulsion in animal body substep discharge, and form slow release effect.And can in florfenicol, add effective ingredients in plant extract or the monomer that improves immunity of organisms, comprise astragalus polysaccharide extract, Radix Isatidis extract, Radix Et Rhizoma Rhei extract and berberine, Sanguinarine, bend Herba Gynurae bicoloris alkali plant monomer in vain, effect is better like this.Described oil for injection can be any in injection soybean oil, injection Oleum Arachidis hypogaeae semen, injection Oleum Gossypii semen, injection Oleum Ricini, the injection Oleum Camelliae.Preparation technology is:
1) get oil for injection 250～500mL, sorbitan fatty acid ester 5～10mL is suspended in sorbitan fatty acid ester in the oil for injection, and is for subsequent use behind 121 ℃ of sterilization 30min;
2) get antibacterials 50～100g, polyoxyethylene sorbitan fatty acid ester 5～10mL is suspended in antibacterials and polyoxyethylene sorbitan fatty acid ester in the water for injection, and is for subsequent use behind 121 ℃ of sterilization 30min;
3) get above-mentioned two kinds of suspensions that prepare and mix, then emulsifying 30～60min prepares the water-in-oil type oil emulsion, and is for subsequent use behind 121 ℃ of sterilization 30min;
4) will be through described technique 3) after the oil emulsion made and soluble starch and the abundant stirring and evenly mixing of methylcellulose to microcapsule granule pulvis microcapsule granule state.
Wherein, florfenicol is present in the water of the described oil emulsion that microcapsule coats or oil, the water two-phase, according to different target animals the characteristics of pharmacokinetics of different antibacterials is adjusted accordingly.
The In Vitro Bacteriostasis effect:
Take the reference culture of escherichia coli, Salmonella, pasteurellosis bacillus and staphylococcus aureus as tested bacterium, utilize doubling dilution, colony counting method to measure MIC and the MBC of florfenicol Emulsion microcapsule, utilize its MPC value of above-mentioned data determination, the results are shown in Figure 1.
Clinical practice:
20% fluorobenzene Buddhist nun Emulsion microcapsule is to the clinical effect trial of porcine contagious pleuropneumonia
1 material
1.1 tested medicine: 20% florfenicol Emulsion microcapsule formulation (specification 100g:20g); Control drug: Florfenicol raw material medicine (content 98%, the Pacific Ocean, Ningxia Biology Pharmacy Co., Ltd, lot number: 200907001).
1.2 test site and time: kind pig farm, Hunan, Henan, Hunan, October in 2011,8 days～December was 25.
1.3 experimental animal: the assorted binary ablactation piglet that grows up, totally 65, in the individual weight 8-10kg scope.
1.4 strain and serotype: Actinobacillus I type standard strain, Actinobacillus I type standard serum is all available from China Veterinery Drug Inspection Office.
2 methods
2.1 animal grouping
60 of the piglets that the selective body heavy phase is near, health status is good are divided into 6 groups at random, isolated rearing, and 10 every group, all test pig basal diet of all feeding every day, regularly drink water every day.The 1st group is the normal healthy controls group, and the 2nd group is the infection matched group, and the 3-5 group is 20% florfenicol Emulsion microcapsule test group, is respectively low dose group, middle dosage group, high dose group, presses 100g/T, and 200g/T, 400g/kg spice feed, and are used in conjunction 3 days.Continue after the drug withdrawal to observe 3 days.The 6th group is the medicine matched group, intramuscular injection 20% florfenicol injection 20mg/kg, and be administered once every day, is used in conjunction 3 times.Continue after the drug withdrawal to observe 3 days.
2.2 artificial challenge and administering mode
After observing 5～7d, the 2nd～6 group of pig is 7 * 10 with bacteria containing amount
8The actinobacillus pleuropneumoniae bacterium drop rhinovaccination 5ml/ head of individual bacterium/ml.The 1st group of collunarium inoculation normal saline 5ml/ head.Behind the artificial challenge 8h, it is slightly depressed to treat that spirit appears in the 2nd～6 group of part pig, and the 3rd～5 group of pig behind the artificial challenge 8h, pressed 100g/T, 200g/T, and the 400g/kg spice is fed, and is used in conjunction 3 days.Continue after the drug withdrawal to observe 3 days.The 6th group of (medicine contrast) intramuscular injection 20% florfenicol injection (20mg/kg) injected 1 time every day, is used in conjunction 3 drug withdrawals.Continuation is observed to artificial and was infected rear the 15th day.See table 2 for details.
The grouping of table 2 test pig and administration situation
2.3 the clinical manifestation of every pig of close observation every day behind the observed content artificial challenge is as breathing the situations of change such as appetite and the mental status.Morbidity number and the death toll of pig respectively organized in record.Dead pig is cutd open inspection, observe lung, liver spleen, the variation of heart, mesentery etc.All dead pigs and off-test rear section pig are slaughtered, get liver, spleen is coated with tryptose soya agar plate culture medium, cultivates 20～48h for 37 ℃, whether check has bacterial growth, to the antibacterial that detects, carry out the series of experiments chamber and detect to check whether be Actinobacillus pleuropneumoniae.
2.4 curative effect is judged and performance assessment criteria:
Cure: offer medicine after 3 days the test pig mental status, appetite, breathing, body temperature each side are all recovered normally, and nothing recurs after the drug withdrawal.The ratio that accounts for this group number according to a healing number is calculated cure rate.
Effectively: offeing medicine, the test pig mental status takes an evident turn for the better after 3 days, appetite increases, slight ventral breathing or cough are arranged.Effective number is total effective number with curing a number sum, and the ratio that accounts for this group test number according to total effective number is calculated total effective rate.
Invalid: the symptoms such as test pig spirit, appetite, breathing, body temperature of offeing medicine after 3 days still do not take a turn for the better even worsen died.The ratio that accounts for this group test number according to invalid number is calculated inefficiency.
3 result of the tests
3.1 clinical symptoms and cut open the inspection artificial challenge after about 8h, each is organized the disease pig and particularly infects the matched group pig, it is depressed to begin spirit to occur, appetite descends, rapid breathing, fever, astasia is reluctant to walk about, sleeping ground is not eaten, mouth breathing or be the dog sitting posture, (about 24h) occurred dehiscing to loll when disease was serious, the color foam liquid death that falls down to the ground of bleeding of last mouth and nose, to 48～72h, it is all dead to infect the matched group pig.Dead pig is cutd open inspection mainly observe pathological changes and be, pneumorrhagia, necrosis, liver are slightly swollen, and there are the downright bad points of many canescence on the surface.Spleen is enlargement slightly, and quality is soft.Intestinal mucosa, duodenal hemorrhage are serious, and intestinal contents contains blood.The opaque weak yellow liquid of volume is arranged in the pericardium, and what have contains cellulose sample exudate.Getting lung, Liver Channel laboratory detects separable to a large amount of actinobacillus pleuropneumoniaes.
3.2 3 dosage groups of therapeutic outcome florfenicol microcapsule agent and medicine matched group all can obviously be resisted the attack of actinobacillus pleuropneumoniae.Pathological change is substantially similar with infection matched group pig, but is the visible strong pneumonia district of chronic pig through death, and there is the adhesive attachment of connective tissue on the surface, and the pneumonia focus becomes gangrenosum acne or suppurative focus.Slightly enlargement of liver, there is downright bad point on the surface.Intestinal mucosa lymph node silght enlargement is hemorrhage.Getting lung, liver spleen is coated with plate and all detects corresponding with it bacterium.Slaughter normal healthy controls group pig, cut open inspection and be showed no any obvious pathological change of observing.See table 3 for details.
Table 3 florfenicol microcapsule curative effect
4 brief summaries
Result of the test shows, florfenicol microcapsule to the therapeutic effect of piglet contagious pleuropneumonia significantly better than florfenicol injection.
Embodiment 2
The preparation prescription of 10% compound enrofloxacin microcapsule is:
Enrofloxacin 100g
Oil for injection 250ml
Span-80 5ml
Tween-80 10ml
Water for injection 350ml
PEG8000 1.0g
Powder solubility 350g
Methylcellulose 80g
This oil emulsion microcapsule coating agent comprises the veterinary antibacterial oil emulsion, and this oil emulsion is pulvis microcapsule granule state, and animal absorbs Emulsion when giving detoxification, and the antibacterials in the Emulsion in animal body substep discharge, and form slow release effect.And can in enrofloxacin, add effective ingredients in plant extract or the monomer that improves immunity of organisms, comprise astragalus polysaccharide extract, Radix Isatidis extract, Radix Et Rhizoma Rhei extract and berberine, Sanguinarine, bend Herba Gynurae bicoloris alkali plant monomer in vain, effect is better like this.Described oil for injection can be any in injection soybean oil, injection Oleum Arachidis hypogaeae semen, injection Oleum Gossypii semen, injection Oleum Ricini, the injection Oleum Camelliae.Preparation technology is:
1) get oil for injection 250～500mL, sorbitan fatty acid ester 5～10mL is suspended in sorbitan fatty acid ester in the oil for injection, and is for subsequent use behind 121 ℃ of sterilization 30min;
2) get antibacterials 50～100g, polyoxyethylene sorbitan fatty acid ester 5～10mL is suspended in antibacterials and polyoxyethylene sorbitan fatty acid ester in the water for injection, and is for subsequent use behind 121 ℃ of sterilization 30min;
3) get above-mentioned two kinds of suspensions that prepare and mix, then emulsifying 30～60min prepares the water-in-oil type oil emulsion, and is for subsequent use behind 121 ℃ of sterilization 30min;
4) will be through described technique 3) after the oil emulsion made and soluble starch and the abundant stirring and evenly mixing of methylcellulose to microcapsule granule pulvis microcapsule granule state.
Wherein, enrofloxacin is present in the water of the described oil emulsion that microcapsule coats or oil, the water two-phase, according to different target animals the characteristics of pharmacokinetics of different antibacterials is adjusted accordingly.
The In Vitro Bacteriostasis effect:
Take the reference culture of escherichia coli, Salmonella, pasteurellosis bacillus and staphylococcus aureus as tested bacterium, utilize doubling dilution, colony counting method to measure MIC and the MBC of florfenicol Emulsion microcapsule, utilize its MPC value of above-mentioned data determination, the results are shown in Figure 1.
Clinical practice:
20% fluorobenzene Buddhist nun Emulsion microcapsule is to the clinical effect trial of porcine contagious pleuropneumonia
1 material
1.1 tested medicine: 20% compound enrofloxacin microcapsule (specification 100g:20g); Control drug: enrofloxacin crude drug (content 98%, the Pacific Ocean, Ningxia Biology Pharmacy Co., Ltd, lot number: 200907001).
1.2 test site and time: kind pig farm, Hunan, Henan, Hunan, October in 2011,8 days～December was 25.
1.3 experimental animal: the assorted binary ablactation piglet that grows up, totally 65, in the individual weight 8-10kg scope.
1.4 strain and serotype: Actinobacillus I type standard strain, Actinobacillus I type standard serum is all available from China Veterinery Drug Inspection Office.
2 methods
2.1 animal grouping
60 of the piglets that the selective body heavy phase is near, health status is good are divided into 6 groups at random, isolated rearing, and 10 every group, all test pig basal diet of all feeding every day, regularly drink water every day.The 1st group is the normal healthy controls group, and the 2nd group is the infection matched group, and the 3-5 group is 20% compound enrofloxacin microcapsule test group, is respectively low dose group, middle dosage group, high dose group, presses 100g/T, and 200g/T, 400g/kg spice feed, and are used in conjunction 3 days.Continue after the drug withdrawal to observe 3 days.The 6th group is the medicine matched group, intramuscular injection 20% enrofloxacin injection 20mg/kg, and be administered once every day, is used in conjunction 3 times.Continue after the drug withdrawal to observe 3 days.
2.2 artificial challenge and administering mode
After observing 5～7d, the 2nd～6 group of pig is 7 * 10 with bacteria containing amount
8The actinobacillus pleuropneumoniae bacterium drop rhinovaccination 5ml/ head of individual bacterium/ml.The 1st group of collunarium inoculation normal saline 5ml/ head.Behind the artificial challenge 8h, it is slightly depressed to treat that spirit appears in the 2nd～6 group of part pig, and the 3rd～5 group of pig behind the artificial challenge 8h, pressed 100g/T, 200g/T, and the 400g/kg spice is fed, and is used in conjunction 3 days.Continue after the drug withdrawal to observe 3 days.The 6th group of (medicine contrast) intramuscular injection 20% enrofloxacin injection (20mg/kg) injected 1 time every day, is used in conjunction 3 drug withdrawals.Continuation is observed to artificial and was infected rear the 15th day.See table 2 for details.
The grouping of table 2 test pig and administration situation
2.3 the clinical manifestation of every pig of close observation every day behind the observed content artificial challenge is as breathing the situations of change such as appetite and the mental status.Morbidity number and the death toll of pig respectively organized in record.Dead pig is cutd open inspection, observe lung, liver spleen, the variation of heart, mesentery etc.All dead pigs and off-test rear section pig are slaughtered, get liver, spleen is coated with tryptose soya agar plate culture medium, cultivates 20～48h for 37 ℃, whether check has bacterial growth, to the antibacterial that detects, carry out the series of experiments chamber and detect to check whether be Actinobacillus pleuropneumoniae.
2.4 curative effect is judged and performance assessment criteria:
Cure: offer medicine after 3 days the test pig mental status, appetite, breathing, body temperature each side are all recovered normally, and nothing recurs after the drug withdrawal.The ratio that accounts for this group number according to a healing number is calculated cure rate.
Effectively: offeing medicine, the test pig mental status takes an evident turn for the better after 3 days, appetite increases, slight ventral breathing or cough are arranged.Effective number is total effective number with curing a number sum, and the ratio that accounts for this group test number according to total effective number is calculated total effective rate.
Invalid: the symptoms such as test pig spirit, appetite, breathing, body temperature of offeing medicine after 3 days still do not take a turn for the better even worsen died.The ratio that accounts for this group test number according to invalid number is calculated inefficiency.
3 result of the tests
3.1 clinical symptoms and cut open the inspection artificial challenge after about 8h, each is organized the disease pig and particularly infects the matched group pig, it is depressed to begin spirit to occur, appetite descends, rapid breathing, fever, astasia is reluctant to walk about, sleeping ground is not eaten, mouth breathing or be the dog sitting posture, (about 24h) occurred dehiscing to loll when disease was serious, the color foam liquid death that falls down to the ground of bleeding of last mouth and nose, to 48～72h, it is all dead to infect the matched group pig.Dead pig is cutd open inspection mainly observe pathological changes and be, pneumorrhagia, necrosis, liver are slightly swollen, and there are the downright bad points of many canescence on the surface.Spleen is enlargement slightly, and quality is soft.Intestinal mucosa, duodenal hemorrhage are serious, and intestinal contents contains blood.The opaque weak yellow liquid of volume is arranged in the pericardium, and what have contains cellulose sample exudate.Getting lung, Liver Channel laboratory detects separable to a large amount of actinobacillus pleuropneumoniaes.
3.2 3 dosage groups of therapeutic outcome compound enrofloxacin microcapsule and medicine matched group all can obviously be resisted the attack of actinobacillus pleuropneumoniae.Pathological change is substantially similar with infection matched group pig, but is the visible strong pneumonia district of chronic pig through death, and there is the adhesive attachment of connective tissue on the surface, and the pneumonia focus becomes gangrenosum acne or suppurative focus.Slightly enlargement of liver, there is downright bad point on the surface.Intestinal mucosa lymph node silght enlargement is hemorrhage.Getting lung, liver spleen is coated with plate and all detects corresponding with it bacterium.Slaughter normal healthy controls group pig, cut open inspection and be showed no any obvious pathological change of observing.See table 3 for details.
Table 3 compound enrofloxacin microcapsule curative effect
4 brief summaries
Result of the test shows, the compound enrofloxacin microcapsule to the therapeutic effect of piglet contagious pleuropneumonia significantly better than enrofloxacin injection.As seen, 10% 'Ennoxacin ' micro-capsule agent character is milky white granules, is convenient to clinical practice.
Embodiment 3
10% sulfanilamide hexakis-methoxy pyrimidine microcapsule
Prescription is:
Sulfanilamide hexakis-methoxy pyrimidine 80g
Oil for injection 500ml
Span-80 8ml
Tween-80 8ml
Water for injection 250ml
PEG8000 1.0g
Soluble starch 500g
Methylcellulose 100g
This oil emulsion microcapsule coating agent comprises the veterinary antibacterial oil emulsion, and this oil emulsion is pulvis microcapsule granule state, and animal absorbs Emulsion when giving detoxification, and the antibacterials in the Emulsion in animal body substep discharge, and form slow release effect.And can in sulfanilamide hexakis-methoxy pyrimidine, add effective ingredients in plant extract or the monomer that improves immunity of organisms, comprise astragalus polysaccharide extract, Radix Isatidis extract, Radix Et Rhizoma Rhei extract and berberine, Sanguinarine, bend Herba Gynurae bicoloris alkali plant monomer in vain, effect is better like this.Described oil for injection can be any in injection soybean oil, injection Oleum Arachidis hypogaeae semen, injection Oleum Gossypii semen, injection Oleum Ricini, the injection Oleum Camelliae.Preparation technology is:
1) get oil for injection 250～500mL, sorbitan fatty acid ester 5～10mL is suspended in sorbitan fatty acid ester in the oil for injection, and is for subsequent use behind 121 ℃ of sterilization 30min;
2) get antibacterials 50～100g, polyoxyethylene sorbitan fatty acid ester 5～10mL is suspended in antibacterials and polyoxyethylene sorbitan fatty acid ester in the water for injection, and is for subsequent use behind 121 ℃ of sterilization 30min;
3) get above-mentioned two kinds of suspensions that prepare and mix, then emulsifying 30～60min prepares the water-in-oil type oil emulsion, and is for subsequent use behind 121 ℃ of sterilization 30min;
4) will be through described technique 3) after the oil emulsion made and soluble starch and the abundant stirring and evenly mixing of methylcellulose to microcapsule granule pulvis microcapsule granule state.
Wherein, sulfanilamide hexakis-methoxy pyrimidine is present in the water of the described oil emulsion that microcapsule coats or oil, the water two-phase, according to different target animals the characteristics of pharmacokinetics of different antibacterials is adjusted accordingly.
In Vitro Bacteriostasis effect and clinical application method are the same, and the curative effect of sulfanilamide hexakis-methoxy pyrimidine microcapsule is as shown in the table:
Result of the test shows, sulfanilamide hexakis-methoxy pyrimidine microcapsule to the therapeutic effect of piglet contagious pleuropneumonia significantly better than sulfanilamide hexakis-methoxy pyrimidine injection.After deliberation, 10% sulfanilamide hexakis-methoxy pyrimidine microcapsule character is milky white granules, is convenient to clinical practice.
Embodiment 4
The preparation of 20% doxycycline hydrochloride microcapsule
Prescription is:
Doxycycline hydrochloride 50g
Oil for injection 300ml
Span-80 10ml
Tween-80 5ml
Water for injection 350ml
PEG8000 1.0g
Soluble starch 450g
Methylcellulose 50g
After deliberation, 20% doxycycline hydrochloride microcapsule character is milky white granules, is convenient to clinical practice.Clinical application method is consistent with embodiment 2, and In Vitro Bacteriostasis effect and embodiment 1 are similar, and final medical effect shows, the doxycycline hydrochloride microcapsule to the therapeutic effect of piglet contagious pleuropneumonia significantly better than doxycycline hydrochloride injection.
In sum, the present invention can be with traditional oils Emulsion oral administration, so that medication is convenient, and medical effect is better than injection.
More than show and described ultimate principle of the present invention and principal character and advantage of the present invention; the technical staff of the industry should understand; the present invention is not restricted to the described embodiments; that describes in above-described embodiment and the description just illustrates principle of the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications; these changes and improvements all fall in the claimed scope of the invention, and the claimed scope of the present invention is defined by appending claims and equivalent thereof.
Claims (9)
1. veterinary antibacterial oil emulsion microcapsule coating agent, it is characterized in that, this microcapsule coating agent of every 1000g contains antibacterials 50～100g, oil for injection 250～500mL, water for injection 250～500mL, PEG1～5g, sorbitan fatty acid ester 5～10mL, polyoxyethylene sorbitan fatty acid ester 5～10mL, soluble starch 250～500g, methylcellulose 50～100g.
2. veterinary antibacterial oil emulsion microcapsule coating agent according to claim 1, it is characterized in that, described veterinary antibacterial oil emulsion microcapsule coating agent comprises the veterinary antibacterial oil emulsion, this oil emulsion is pulvis microcapsule granule state, animal absorbs Emulsion when giving detoxification, antibacterials in the Emulsion in animal body substep discharge, and form slow release effect.
3. veterinary antibacterial oil emulsion microcapsule coating agent according to claim 1 is characterized in that described PEG is PEG5000-PEG8000.
4. veterinary antibacterial oil emulsion microcapsule coating agent according to claim 1 is characterized in that, described antibacterials are enrofloxacin, sulfanilamide hexakis-methoxy pyrimidine, doxycycline hydrochloride or florfenicol.
5. veterinary antibacterial oil emulsion microcapsule coating agent according to claim 1 is characterized in that described antibacterials are compound medicine.
6. veterinary antibacterial oil emulsion microcapsule coating agent according to claim 5, it is characterized in that, in described antibacterials, add to improve effective ingredients in plant extract or the monomer of immunity of organisms, comprise astragalus polysaccharide extract, Radix Isatidis extract, Radix Et Rhizoma Rhei extract and berberine, Sanguinarine, bend Herba Gynurae bicoloris alkali plant monomer in vain.
7. veterinary antibacterial oil emulsion microcapsule coating agent according to claim 1 is characterized in that, described oil for injection is injection soybean oil, injection Oleum Arachidis hypogaeae semen, injection Oleum Gossypii semen, injection Oleum Ricini or injection Oleum Camelliae.
8. the preparation method of each described veterinary antibacterial oil emulsion microcapsule coating agent of claims 1 to 3 is characterized in that, comprises following preparation technology:
1) according to claim 1 proportioning prepares the suspendible oil phase: sorbitan fatty acid ester is suspended in the oil for injection, and for subsequent use behind 121 ℃ of sterilization 30min;
2) according to claim 1 proportioning prepares the suspendible oil phase: antibacterials and polyoxyethylene sorbitan fatty acid ester are suspended in the water for injection, and for subsequent use behind 121 ℃ of sterilization 30min;
3) get above-mentioned two kinds of suspensions and mix, then emulsifying 30～60min prepares the water-in-oil type oil emulsion, and is for subsequent use behind 121 ℃ of sterilization 30min;
4) will be through described technique 3) after the oil emulsion made and soluble starch and the abundant stirring and evenly mixing of methylcellulose to microcapsule granule pulvis microcapsule granule state.
9. preparation method according to claim 8 is characterized in that, antibacterials are present in the water of the described oil emulsion that microcapsule coats or oil, the water two-phase, according to different target animals the characteristics of pharmacokinetics of different antibacterials are adjusted accordingly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012105815813A CN103054833A (en) | 2012-12-28 | 2012-12-28 | A formula of an antimicrobial oil emulsion microcapsule for veterinary use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012105815813A CN103054833A (en) | 2012-12-28 | 2012-12-28 | A formula of an antimicrobial oil emulsion microcapsule for veterinary use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103054833A true CN103054833A (en) | 2013-04-24 |
Family
ID=48097933
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012105815813A Pending CN103054833A (en) | 2012-12-28 | 2012-12-28 | A formula of an antimicrobial oil emulsion microcapsule for veterinary use |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103054833A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103356690A (en) * | 2013-06-09 | 2013-10-23 | 四川英格瑞生物科技有限公司 | Injection for treating sow endometritis and preparation method thereof |
| CN103919861A (en) * | 2014-04-30 | 2014-07-16 | 张传津 | Chinese-Western medicine compound transdermal emulsion for preventing and treating colibacillosis of piglets and preparation method thereof |
| CN108524466A (en) * | 2018-07-02 | 2018-09-14 | 合肥中龙神力动物药业有限公司 | A kind of florfenicol microcapsule preparation and preparation method thereof |
| CN108524467A (en) * | 2018-07-02 | 2018-09-14 | 合肥中龙神力动物药业有限公司 | A kind of composite sulfamonomethoxine sodium microcapsule formulation and preparation method thereof |
| CN114129635A (en) * | 2021-10-28 | 2022-03-04 | 湖南农业大学 | Antibacterial composition containing Capsici fructus extract and its application |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102119923A (en) * | 2011-02-25 | 2011-07-13 | 湖南农业大学 | Antibiotic oil-water double suspension type injection emulsion for livestock and preparation method thereof |
-
2012
- 2012-12-28 CN CN2012105815813A patent/CN103054833A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102119923A (en) * | 2011-02-25 | 2011-07-13 | 湖南农业大学 | Antibiotic oil-water double suspension type injection emulsion for livestock and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 朱静等: "微囊化双层包被技术在兽药领域的研究应用", 《兽药市场指南》 * |
| 汤法银: "复方牛至油口服乳剂的研制", 《中国优秀硕士学位论文全文数据库 农业科技辑》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103356690A (en) * | 2013-06-09 | 2013-10-23 | 四川英格瑞生物科技有限公司 | Injection for treating sow endometritis and preparation method thereof |
| CN103356690B (en) * | 2013-06-09 | 2015-02-25 | 四川英格瑞生物科技有限公司 | Injection for treating sow endometritis and preparation method thereof |
| CN103919861A (en) * | 2014-04-30 | 2014-07-16 | 张传津 | Chinese-Western medicine compound transdermal emulsion for preventing and treating colibacillosis of piglets and preparation method thereof |
| CN103919861B (en) * | 2014-04-30 | 2016-06-15 | 济南百鸣生物制药有限公司 | Compound percutaneous Emulsion of Chinese medicine and western medicine of preventing and treating colibacillosis of piglet and preparation method thereof |
| CN108524466A (en) * | 2018-07-02 | 2018-09-14 | 合肥中龙神力动物药业有限公司 | A kind of florfenicol microcapsule preparation and preparation method thereof |
| CN108524467A (en) * | 2018-07-02 | 2018-09-14 | 合肥中龙神力动物药业有限公司 | A kind of composite sulfamonomethoxine sodium microcapsule formulation and preparation method thereof |
| CN114129635A (en) * | 2021-10-28 | 2022-03-04 | 湖南农业大学 | Antibacterial composition containing Capsici fructus extract and its application |
| CN114129635B (en) * | 2021-10-28 | 2022-11-04 | 湖南农业大学 | Antibacterial composition containing capsicum extract and its application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103006792B (en) | A kind of herbal medicine for preventing and treating livestock and poultry intestinal canal diseases and preparation method thereof and feed | |
| CN101836691B (en) | Chinese medicinal herb feed additive | |
| CN102670516A (en) | Tilmicosin soluble powder and preparation method thereof | |
| CN103054833A (en) | A formula of an antimicrobial oil emulsion microcapsule for veterinary use | |
| CN102119923B (en) | Antibiotic oil-water double suspension type injection emulsion for livestock and preparation method thereof | |
| CN102028795B (en) | Chinese pulsatilla root granules for preventing and treating livestock and poultry bacterial diseases and preparation method and premix thereof | |
| CN101496811B (en) | Soluble and stable tilmicosin composition | |
| CN102885201A (en) | Compound Chinese herbal medicine feed additive | |
| CN102283842A (en) | Compound mequindox florfenicol nanoemulsion antibacterial drug and preparation method thereof | |
| CN101780227A (en) | Traditional Chinese medicine composition for treating acute stroke and preparation method thereof | |
| CN102697725B (en) | Veterinary ciprofloxacin lactate injection and preparation method thereof | |
| CN102614294A (en) | Compound amoxicillin suspension injection and preparation method thereof | |
| CN105231054A (en) | Medicinal feedstuff preventing and treating mink cold disease | |
| CN102755342B (en) | Compound paracetamol injection and preparation method thereof | |
| CN103610768B (en) | Composition for treating colibacillosis | |
| CN103893300B (en) | A kind of Chinese medicine composition treating cow endometritis and preparation method and application | |
| CN109432287B (en) | Traditional Chinese medicine oral liquid for preventing and treating excessive heat syndrome of poultry qi system and preparation method thereof | |
| CN102488648A (en) | Preparation method of florfenicol self-microemulsion | |
| CN103417477B (en) | A kind of take water as doractin O/W type injection of substrate and preparation method thereof | |
| CN108403631A (en) | Ten thousand rhzomorph oil mixed suspension injections of tartaric acid Thailand and preparation method thereof | |
| CN103463202B (en) | Oral traditional Chinese medicine preparation for treating acne and production process of oral traditional Chinese medicine preparation for treating acne | |
| CN109106694A (en) | A kind of flunixin meglumine microcapsule formulation and preparation method thereof | |
| CN103007270B (en) | Injection injected into acupoint Houhai to treat piglet diarrhea | |
| CN102846781A (en) | Veterinary drug containing Chinese medicines for treating coccidiosis in poultry | |
| CN102309563A (en) | Medicinal preparation used for treating diarrhoea of livestock and poultry |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20130424 |