CN103919861B - Compound percutaneous Emulsion of Chinese medicine and western medicine of preventing and treating colibacillosis of piglet and preparation method thereof - Google Patents
Compound percutaneous Emulsion of Chinese medicine and western medicine of preventing and treating colibacillosis of piglet and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a kind of compound percutaneous Emulsion of Chinese medicine and western medicine preventing and treating colibacillosis of piglet and preparation method thereof. The composition of this transdermal Emulsion is: Herba Macleayae Cordatae extract, florfenicol, laurocapram, Arlacel-80, tween 80, aluminium stearate, sodium carboxymethyl cellulose, vitamin E, injection soybean oil and purified water. It is after soybean oil dry heat sterilization, will to be added wherein by aluminium stearate, add Arlacel-80, add vitamin E, make oil phase standby after sterilized; Sodium carboxymethyl cellulose is added in purified water, add Herba Macleayae Cordatae extract and florfenicol after adding tween 80 and laurocapram dissolving after dissolving, be down to room temperature after sterilizing standby as aqueous phase; Oil phase enters emulsion tank through pipeline, adds aqueous phase, adds continuation stirring and forms colostrum, and colostrum adds colloid mill emulsification pretreatment and get final product. The clinical prevention effect of colibacillosis of piglet is shown, said preparation cure rate reaches more than 90%, hence it is evident that be better than single use of western medicine or Chinese medicine.
Description
Technical field
The invention belongs to preventing and treating colibacillosis of piglet class technical field of pharmaceuticals, specifically a kind of compound percutaneous Emulsion of Chinese medicine and western medicine preventing and treating colibacillosis of piglet and preparation method thereof.
Background technology
Yellow scour of piglet, Hakuri are the intestine of young pigs infectious disease caused by Escherichia coli. Yellow scour of piglet is several hours acute height lethal infectious intestinal diseases of the one to 1 week old piglet after birth, with violent diarrhoea, discharges yellow or yellow-white watery stools and rapid dehydration death is feature, is one of the primary bowel disease of Compact Develop. Piglet pujos blancos is a kind of acute infectious intestinal disease that 10-30 age in days piglet is multiple, to discharge canescence thickness loose stool for feature, it is common to betide countries in the world, often cause large quantities of piglet dysplasia or death, cause heavy losses to animal husbandry.
At present this disease mainly being had to the immunity of vaccine, the mode such as antibiotic, chemicals, Chinese medicine carries out preventing and treating. Wherein vaccine immunization, because enteric microorganism antigen and antigenic determinant are complicated, immunologic mechanism is difference slightly, and immune effect is imprecise. Along with antibacterials abuse clinically, cause that the drug resistance of the antibacterials such as escherichia coli is very general, as the curative effect of medication such as gentamycin conventional clinically, oxytetracycline, norfloxacin, norfloxacin reduce. Comparing with other prevention, Therapeutic Method, Chinese herbal medicine has non-specific antimicrobial effect. and residual toxicity is relatively low, and it is generally not likely to produce drug resistance by animal. And Chinese medicine and Western medicine are carried out effective compatibility, it is possible to slow down the generation of Resistant strain.
Along with the development of intensive breeding scale, select optimum route of administration very crucial. Treatment intestinal infection, makes liniment by medicine, by transdermal administration, compares with general formulation (such as oral tablet, injection etc.) and have following characteristics: 1. can avoid the contingent first pass effect of hepar of oral administration and gastrointestinal inactivation;2. can maintain constant optimum blood medicine concentration, reduce the side effect of gastro-intestinal administration; 3. extend effective acting time, reduce administration number of times; 4. by changing administration area adjustment dosage, interindividual variation is reduced.
Summary of the invention
Present invention aims to antibiotic unreasonable use on current veterinary clinic, a kind of compound percutaneous Emulsion of Chinese medicine and western medicine preventing and treating colibacillosis of piglet and preparation method thereof is provided, this compound preparation selects effective components of Chinese medicinal extract, scientific compatibility is carried out with Western medicine, by drug combination to reduce bacterial drug resistance and drug dose, its clinical prevention colibacillosis of piglet effect is better than simple Chinese medicine or Western medicine, has good market prospect.
The technical scheme is that a kind of compound percutaneous Emulsion of Chinese medicine and western medicine preventing and treating colibacillosis of piglet, it is characterized in that, the compound percutaneous Emulsion of Chinese medicine and western medicine of described every 100ml comprises following components: Herba Macleayae Cordatae extract 1～5g, florfenicol 5～10g, laurocapram 2～5g, Arlacel-80 3～6g, tween 80 2～4g, aluminium stearate (oil phase stabiliser) 0.5～2g, sodium carboxymethyl cellulose (aqueous phase stability agent) 0.1～0.5g, vitamin E 0.1～1g, injection soybean oil 52g, purified water adds to 100ml.
Optimum ratio is: Herba Macleayae Cordatae extract 5g, florfenicol 5g, laurocapram 2g, Arlacel-80 4g, tween 80 4g, aluminium stearate 1g, sodium carboxymethyl cellulose 0.5g, vitamin E 0.5g, and injection soybean oil 52g, purified water adds to 100ml.
Described Herba Macleayae Cordatae extract, purification extracted by Herba Macleayae Cordatae, concentration, the dry Chinese medicine extract prepared, principle active component is Sanguinarine (C20H14NO4) and chelerythrine (C21H18NO4), the two total amount is no less than 60.0% (w/w).
The preparation method that it is a further object to provide a kind of compound percutaneous preparation preventing and treating colibacillosis of piglet. Specifically include following steps:
(1) preparation of oil phase
Aluminium stearate, Arlacel-80, vitamin E and soybean oil is weighed by said ratio, by after 150 DEG C～160 DEG C dry heat sterilizations of soybean oil 1～2 hour, when being down to 60～70 DEG C, aluminium stearate is slowly added in soybean oil, and is stirred continuously to being completely dissolved to transparence, add Arlacel-80 mix homogeneously, 100-120 DEG C of sterilizing 20-40 minute, is down to less than 65 DEG C, adds vitamin E, stir, make oil phase standby;
(2) preparation of aqueous phase
Sodium carboxymethyl cellulose, Herba Macleayae Cordatae extract, florfenicol, tween 80 and laurocapram is weighed by said ratio; Sodium carboxymethyl cellulose is added in purified water, heating makes it be dissolved to transparence, add tween 80, laurocapram adds Herba Macleayae Cordatae extract, florfenicol after dissolving, mixed at least 10 minutes to (1000rmp/min) at a high speed by low speed (500rmp/min), 100-120 DEG C of sterilizing 20-40 minute, is down to room temperature standby as aqueous phase;
(3) emulsifying
Oil phase enters emulsion tank through pipeline, is slowly added to aqueous phase, stirring while adding, adds continuation stirring 5-8min and becomes colostrum, and colostrum adds colloid mill emulsification pretreatment 15～30 minutes, obtains milky transdermal Emulsion. Sampling, 12000r/min is centrifuged 15min, and observation should not breakdown of emulsion.
Usage and consumption
Treatment: smear percutaneous drug delivery, embrocate in ill pig back near root of the tail place, 1 age in days is to every the 1～2ml that weans; To 20kg after wean, every 1kg body weight 0.2ml, once-a-day. It is used in conjunction 3～5.
The effect duration of medicine: room temperature lower seal shading preserves, 24 months effect duration.
Each crude drug source and pharmacological action
Herba Macleayae Cordatae: the fruit of bloodroot Herba Macleayae Cordatae (Macleayacordata (Willd.) R.Br.). In Herba Macleayae Cordatae, effective ingredient is mainly Sanguinarine (sanguinarine) and chelerythrine (chelerythrine), the highest with content in fruit. Herba Macleayae Cordatae has stronger sterilization, bacteriostatic activity, extracorporeal bacteria inhibitor test and veterinary clinic test show, escherichia coli minimum inhibitory concentration (MIC) is 7.81ug/mL by Herba Macleayae Cordatae extract, the total effective rate for the treatment of yellow scour of piglet and Hakuri reaches 80%, and have that consumption is little, low cost and other advantages, in the loaded Ministry of Agriculture 96 editions " veterinary medical quality standard ".
Florfenicol (Florfenicol): Chinese: fluprofen; Florfenicol; Florfenicol, chemical name: [R--(R1.T)]-2,2-bis-chloro-N-{ methyl fluoride)-2-hydroxyl-2-[4-(sulfonyloxy methyl) phenyl] ethyl } acetamide. Florfenicol is the broad spectrum antibiotic of a kind of new special chloromycetin of veterinary successfully developed in the late nineteen eighties. Florfenicol is the structure homologues of chloromycetin, can be combined with 50S subunit, it is suppressed that phthaloyl based transferase, thus suppressing the extension of phthalein chain, interferencing protein synthesizes.-the OH that florfenicol structurally instead of in chloromycetin, thiamphenicol on propane chain 3 carbon location with F atom, prevents antibacterial Acetylase acetylation on this position, therefore is not affected by this enzyme and be inactivated; And Acetylase is relevant through the plasmid-mediated drug resistance to chloromycetin, thiamphenicol with antibacterial, therefore florfenicol will not produce the drug resistance that similar chloromycetin, thiamphenicol are plasmid-mediated, and many chloramphenicol resistance bacterial strains are still sensitive. Chloromycetin is with the untoward reaction of serious induced aplastic anemia, and many countries have forbidden chloromycetin use on animal diseases control, and especially food animal, such as U.S. FDA. Research shows, in chloromycetin structure, on aromatic rings, para-position nitro is the essential groups causing aplastic anemia, and florfenicol is structurally with H3C-SO2-instead of O2N-, does not produce the untoward reaction of aplastic anemia after medication, therefore on animal diseases control, especially food animal, florfenicol will substitute chloromycetin, have broad prospect of application at veterinary clinic.
The horny layer of skin is the first barrier directly contacted with vitro. It is generally believed that for fat-soluble stronger medicine, the cuticular barrier action of skin is relatively small, and the bigger medicine of the medicine that molecular weight is bigger, polarity or water solublity is then more difficult passes through. The molecular weight material more than 600 is more difficult passes through horny layer. Drug diffusion coefficient is directly proportional to the square root of molecular weight, and molecular weight is bigger, and molecular volume is bigger, and diffusion coefficient is then less. Medicine that fusing point is higher and water solublity or hydrophilic medicament, relatively low in cuticular permeability. Florfenicol molecular weight is 358.2, florfenicol very easily dissolves in dimethylformamide, almost insoluble in water, is fat-soluble medicine, the fusing point of florfenicol is also relatively low (152-156 DEG C), so florfenicol possesses the primary condition making Percutaneously administrable preparation. Sanguinarine molecular weight is 332.3, chelerythrine molecular weight is 348.3 (< 600), also it is fat-soluble biological bases, is aided with excellent penetration enhancer laurocapram, accelerate florfenicol and penetrate through skin with little molecular biosciences alkali.
The invention has the beneficial effects as follows: according to Chinese veterinarian's rationale, pathogeny in conjunction with colibacillosis of piglet, the feature of drug resistance it is easily generated for e. coli serotype complexity, prescription screening is carried out in conjunction with clinical practice by drug sensitivity testing in vitro, by Chinese medicine extract and florfenicol use in conjunction, in-vitro antibacterial effect shows, has good synergism.
The medication object of this product is limited to the piglet of below 20kg, smearing position selects pig body mesocuticle than relatively thin position: be applied to pig back near root of the tail place, this is that permeability is higher than middle pig, gears to actual circumstances owing in the cuticular thickness ratio of piglet, pig or big pig are thin. Clinical practice proves, this product is harmless to skin or stimulates side effect, lasting medicine, determined curative effect, blood drug level is constant, and times for spraying reduces, the clinical prevention effect of colibacillosis of piglet is shown, the effective percentage of said preparation reaches 100%, and cure rate reaches more than 90%, hence it is evident that be better than single use of western medicine or Chinese medicine. In a word, this research, by Chinese and western drugs use in conjunction, not only can reduce florfenicol dosage, and can reduce the generation of bacterial drug resistance, thus reducing drug cost, reducing drug residue.
Detailed description of the invention
Embodiment 1
Proportioning: Herba Macleayae Cordatae extract 5g, florfenicol 5g, laurocapram 2g, Arlacel-80 4g, Tween 80 4g, aluminium stearate 1g, sodium carboxymethyl cellulose 0.5g, vitamin E 0.5g, injection soybean oil 52g, purified water adds to 100ml.
Described Herba Macleayae Cordatae extract, is produced by Hunan Micolta Bioresource Inc., lot number: 2013051201, be that Herba Macleayae Cordatae is extracted, purification, concentration, the dry Chinese medicine extract prepared, principle active component is Sanguinarine (C20H14NO4) and chelerythrine (C21H18NO4), its total amount is no less than 60.0% (w/w).
Preparation method:
(1) aluminium stearate, Arlacel-80, vitamin E and soybean oil are weighed by said ratio, by after 150 DEG C～160 DEG C dry heat sterilizations of soybean oil 1～2 hour, when being down to 60～70 DEG C, aluminium stearate is slowly added in soybean oil, and is stirred continuously to being completely dissolved to transparence, add Arlacel-80 mix homogeneously, 115 DEG C of sterilizings 30 minutes, are down to less than 65 DEG C, add vitamin E, stir, make oil phase standby;
(2) sodium carboxymethyl cellulose, Herba Macleayae Cordatae extract, florfenicol, tween 80 and laurocapram are weighed by said ratio again; Sodium carboxymethyl cellulose is added in purified water, heating makes it be dissolved to transparence, add tween 80, laurocapram adds Herba Macleayae Cordatae extract, florfenicol after dissolving, mixed at least 10 minutes to (1000rmp/min) at a high speed by low speed (500rmp/min), 115 DEG C of sterilizings 30 minutes, are down to room temperature standby as aqueous phase;
(3) oil phase enters emulsion tank through pipeline, is slowly added to aqueous phase, stirring while adding, adds continuation stirring 5-8min and becomes colostrum, and colostrum adds colloid mill emulsification pretreatment 15～30 minutes, obtains milky transdermal Emulsion. Sampling, 12000r/min is centrifuged 15min, and observation should not breakdown of emulsion.
Obtained transdermal Emulsion is milky oil emulsion body, and mean diameter, between 10-60 μm, meets the emulsion grain specification of States Pharmacopoeia specifications.
Obtained Emulsion is stored 10 days and, not breakdown of emulsion not stratified with the centrifugal 15min of 12000r/min at 37 DEG C, it was shown that it has good stability, and can close and keep in Dark Place more than 1 year.
Below in conjunction with clinical practice experimental data, its therapeutic effect is described.
1 test material
1.1 trial drugs: the compound percutaneous preparation of Chinese medicine and western medicine of embodiment 1 preparation.
1.2 control drug: florfenicol injection, specification: 10ml:0.2g, lot number: 030213, Shandong Zhong Mu veterinary drug company limited.
1.3 test pig: suffer from the natural occurrence piglet of HUANGBAI(sic) dysentery, farm, Jinan 61 provides.
1.4 strains: swine escherichia coli O8、O64、O101Strain, China Veterinery Drug Inspection Office.
1.5 culture medium: nutrient broth, maconkey agar flat board, make according to a conventional method.
2 test methods
2.1 Pathogen identification: gather pathological material of disease with disinfecting silk or cotton swab from the deep, straight chamber suffering from the natural occurrence piglet having loose bowels, carry out bacteria distribution, cultivation and qualification, whether to make a definite diagnosis for yellow and white dysentery of piglet.
2.2 extracorporeal bacteria inhibitor tests: conventional paper disk method carries out.
2.3 antibacterial result criterion: average antibacterial circle diameter < 10mm is hypoallergenic, and 10-15mm is quick in being, 15-20mm is Gao Min, > 20mm is extremely quick, and conventional method carries out.
2.4 clinical trials and observation of curative effect
2.4.1 packet is tested: be randomly divided into 5 groups by making a definite diagnosis the natural occurrence piglet suffering from HUANGBAI(sic) dysentery. I, II, III group is the high, medium and low treatment group of trial drug, presses 2ml/ head, 1ml/ head, the administration of 0.5ml/ head respectively, embrocates in ill pig back near root of the tail place, every day 1 time, be used in conjunction 3. IV group is florfenicol injection matched group, 0.1ml/Kg body weight, intramuscular injection, every day 2 times, is used in conjunction 3 days. V group is safety test group, embrocates administration by 5ml/ head pig back. Each test group isolated rearing, intensive care.
2.4.2 observation of curative effect: Continuous Observation 15 days after medication, each group feeds pig perfect compound feed (without any antibacterials), notes observing defecation number of times and feces state during test.
2.4.3 result of the test statistics: add up each group of mortality rate, effective percentage, cure rate during off-test, carry out X between each group2Inspection.
2.4.4 curative effect judging standard:
Recovery from illness: the spirit of affected pig after treatment, appetite recover normal, and feces be strip or graininess, anus dries, shrinks, without redness, without rebound phenomenon in seven days.
Effective: feces retrogradation after treatment, defecation frequency reduces, and anus redness does not disappear completely, and spirit appetite makes moderate progress.
Invalid: after treatment, affected pig spirit, feces, appetite are not improved, even dead.
3 result of the tests
3.1 extracorporeal bacteria inhibitor test results
Extracorporeal bacteria inhibitor test result shows, the in-vitro antibacterial of pig Enteropathogenic Escherichia coli is had synergism (average antibacterial circle diameter is 17.3mm) by florfenicol and Herba Macleayae Cordatae extract, to swine escherichia coli Gao Min, apparently higher than florfenicol injection (average antibacterial circle diameter is 11.7mm), result is in Table 1.
Table 1 extracorporeal bacteria inhibitor test result
The qualification of 3.2 clinical disease pigs
Choosing 55 piglets having symptom of having loose bowels from the swinery of 11 nest 15-20 ages in days, its Symptoms is: discharge white or milky is stuck with paste, pulpous state loose stool, loss of appetite, and the sick pig back of a bow by hair slightly disorderly, is slow in action. Inside 5 sick pig anuses, gather experimental material with disinfecting silk or cotton swab respectively, after cotton swab is inoculated nutrient broth Zengjing Granule, Mai Kangkai differential medium is rule, see and have a large amount of uniform red colonies to grow, picking colony, smear, dyeing, microscopy is Gram-negative brevibacterium. Gavage (1,000,000,000 CFU/ head) with broth culture to pig, similar symptoms occurred in after infection 12-24 hour, in conjunction with facing the feature of examining, be diagnosed as piglet Huang, Hakuri.
3.3 clinical treatment outcome
After testing 2 days, trial drug group diarrhea of pigs symptom alleviates. 4th day, except still suffering from diarrhoea except the low dosage indivedual pig of trial drug group, major part diarrhea of pigs stopped.5th day, whole pigs stopped diarrhoea, and spirit takes a turn for the better, and appetite is recovered. After florfenicol injection group medication 1 day, diarrhea of pigs symptom alleviates, illustrate that florfenicol injection effective blood drug concentration peak time is faster than transdermal agent, but transdermal agent times for spraying is few, medication is convenient, avoid the blood drug level peak valley undulatory property that repeatedly medication produces one, extend action time, have the advantage of uniqueness. Result of the test is in Table 2.
Table 2 trial drug treatment yellow and white dysentery of piglet statistical effect table
To the healing number of each group with do not cure number and carry out X2Inspection: I, II, III group of X to IV group2Value respectively 11.05,11.05 (> 6.63, difference is extremely notable), 6.04 (> 3.84, significant differences); I couple of II X2Value be 0 (< 3.84, difference is not notable; The X of II couple III2Value is 5.35 (> 3.84, significant differences).
Biometric, it is shown that obvious difference between each dosage group of trial drug and control drug group, illustrates that the prevention effect of yellow and white dysentery of piglet is better than florfenicol injection by trial drug. Between trial drug dose group high, middle, difference is not notable, and from the viewpoint of cure rate and medicine cost etc., clinical practice is suitable with middle dosage group.
3.4 drug safety analyses
Not affecting the spirit of test pig, appetite with 5 multiple dose medications of recommended dose, growth promoter is normal, and pig body surface coating position does not show visible clinical irritative response and pathological changes, and safety testing shows that pig is safe by investigational agent.
3.5 conclusion (of pressure testing)s
Medicaments compound preparation capable of permeating skin of the present invention by Herba Macleayae Cordatae extract, florfenicol science is composite forms, the treatment of yellow and white dysentery of piglet there is good effect, and it is few to have times for spraying, medication is convenient, avoid the blood drug level peak valley undulatory property that repeatedly medication produces one, extend the unique advantage of action time. Recommended dose, for smearing percutaneous drug delivery, is embrocated in ill pig back near root of the tail place, and 1 age in days is to every the 1～2ml that weans, once-a-day; To 20kg after wean, every 1kg body weight 0.2ml, once a day.
Embodiment 2
Proportioning: Herba Macleayae Cordatae extract 2g, florfenicol 8g, laurocapram 3g, Arlacel-80 5g, Tween 80 2g, aluminium stearate 1g, sodium carboxymethyl cellulose 0.2g, vitamin E 0.2g, injection soybean oil 52g, purified water adds to 100ml.
Preparation method is with embodiment 1.
Embodiment 3:
Proportioning: Herba Macleayae Cordatae extract 3g, florfenicol 7g, laurocapram 3g, Arlacel-80 4g, Tween 80 3g, aluminium stearate 1.5g, sodium carboxymethyl cellulose 0.3g, vitamin E 0.5g, injection soybean oil 52g, purified water adds to 100ml.
Preparation method is with embodiment 1.
Embodiment 4
Proportioning: Herba Macleayae Cordatae extract 4g, florfenicol 6g, laurocapram 4g, Arlacel-80 5g, Tween 80 4g, aluminium stearate 2g, sodium carboxymethyl cellulose 0.3g, vitamin E 0.2g, injection soybean oil 52g, purified water adds to 100ml.
Preparation method is with embodiment 1.
Claims (2)
1. preventing and treating the compound percutaneous Emulsion of Chinese medicine and western medicine of colibacillosis of piglet, it is characterized in that, the compound percutaneous Emulsion of Chinese medicine and western medicine of described every 100ml comprises following components: Herba Macleayae Cordatae extract 1～5g, florfenicol 5～10g, laurocapram 2～5g, Arlacel-80 3～6g, tween 80 2～4g; Aluminium stearate 0.5～2g, sodium carboxymethyl cellulose 0.1～0.5g, vitamin E 0.1～1g, injection soybean oil 52g, purified water adds to 100ml; The principle active component of described Herba Macleayae Cordatae extract is Sanguinarine and chelerythrine, and the two total amount is no less than 60.0% (w/w);
It is prepared from by following method:
(1) preparation of oil phase
Weigh aluminium stearate, Arlacel-80, vitamin E and soybean oil according to the above ratio, by after 150 DEG C～160 DEG C dry heat sterilizations of soybean oil 1～2 hour, when being down to 60～70 DEG C, aluminium stearate is slowly added in soybean oil, and is stirred continuously to being completely dissolved to transparence, add Arlacel-80 mix homogeneously, it is down to less than 65 DEG C after 20-40 minute through 100-120 DEG C of sterilizing, add vitamin E, stir, make oil phase standby;
(2) preparation of aqueous phase
Weigh sodium carboxymethyl cellulose, Herba Macleayae Cordatae extract, florfenicol, tween 80 and laurocapram according to the above ratio; Sodium carboxymethyl cellulose is added in purified water, heating makes it be dissolved to transparence, add and after tween 80 and laurocapram dissolve, add Herba Macleayae Cordatae extract and florfenicol, stirring mixing at least 10 minutes, it is down to room temperature through 100-120 DEG C of sterilizing after 20-40 minute standby as aqueous phase;
(3) emulsifying
Oil phase enters emulsion tank through pipeline, is slowly added to aqueous phase, stirring while adding, adds continuation stirring 5-8min and becomes colostrum, and colostrum adds colloid mill emulsification pretreatment 15～30 minutes, obtains transdermal Emulsion.
2. the compound percutaneous Emulsion of Chinese medicine and western medicine preventing and treating colibacillosis of piglet as claimed in claim 1, it is characterized in that, the compound percutaneous Emulsion of Chinese medicine and western medicine of described every 100ml comprises following components: Herba Macleayae Cordatae extract 5g, florfenicol 5g, laurocapram 2g, Arlacel-80 4g, tween 80 4g, aluminium stearate 1g, sodium carboxymethyl cellulose 0.5g, vitamin E 0.5g, injection soybean oil 52g, purified water adds to 100ml.
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| CN103054833A (en) * | 2012-12-28 | 2013-04-24 | 湖南农业大学 | A formula of an antimicrobial oil emulsion microcapsule for veterinary use |
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| 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 |
| CN103054833A (en) * | 2012-12-28 | 2013-04-24 | 湖南农业大学 | A formula of an antimicrobial oil emulsion microcapsule for veterinary use |
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Effective date of registration: 20160510 Address after: 250116, No. 18, Wei village, Dang Zhuang Town, Shizhong District, Shandong City, Ji'nan Province Applicant after: Jinan Baiming Bio-Pharmaceutical Co., Ltd. Address before: Huai Village Street Huaiyin District of Ji'nan city of Shandong Province, No. 68 250022 Applicant before: Zhang Chuanjin |
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Address after: No. 2988, Jichang West Road, high tech Zone, Jinan City, Shandong Province Patentee after: Jinan Baiming Bio-Pharmaceutical Co., Ltd. Address before: 250116, No. 18, Wei village, Dang Zhuang Town, Shizhong District, Shandong City, Ji'nan Province Patentee before: Jinan Baiming Bio-Pharmaceutical Co., Ltd. |