CN103977006B - A kind of pharmaceutical composition treating mammitis of cow and its production and use - Google Patents
A kind of pharmaceutical composition treating mammitis of cow and its production and use Download PDFInfo
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- CN103977006B CN103977006B CN201410239009.8A CN201410239009A CN103977006B CN 103977006 B CN103977006 B CN 103977006B CN 201410239009 A CN201410239009 A CN 201410239009A CN 103977006 B CN103977006 B CN 103977006B
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- enrofloxacin
- mannitol
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- 208000004396 mastitis Diseases 0.000 title claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 title abstract description 5
- 229960000740 enrofloxacin Drugs 0.000 claims abstract description 62
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 claims abstract description 61
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 35
- 229930195725 Mannitol Natural products 0.000 claims abstract description 34
- 239000000594 mannitol Substances 0.000 claims abstract description 34
- 235000010355 mannitol Nutrition 0.000 claims abstract description 34
- 239000003814 drug Substances 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 17
- 239000000890 drug combination Substances 0.000 claims abstract description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 239000007924 injection Substances 0.000 claims description 10
- 238000002347 injection Methods 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 7
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 6
- 229930003268 Vitamin C Natural products 0.000 claims description 6
- 235000019154 vitamin C Nutrition 0.000 claims description 6
- 239000011718 vitamin C Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000008215 water for injection Substances 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 238000005374 membrane filtration Methods 0.000 claims 2
- 235000013336 milk Nutrition 0.000 abstract description 16
- 210000004080 milk Anatomy 0.000 abstract description 16
- 239000008267 milk Substances 0.000 abstract description 15
- 208000024891 symptom Diseases 0.000 abstract description 2
- 241000283690 Bos taurus Species 0.000 description 33
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 14
- 210000000481 breast Anatomy 0.000 description 10
- 229940090044 injection Drugs 0.000 description 8
- 229960003405 ciprofloxacin Drugs 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 229940080526 mannitol injection Drugs 0.000 description 5
- 206010030113 Oedema Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- 235000013365 dairy product Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 206010060710 Galactostasis Diseases 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 210000005075 mammary gland Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 208000031462 Bovine Mastitis Diseases 0.000 description 1
- 206010006298 Breast pain Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000006662 Mastodynia Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000012173 estrus Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229940093181 glucose injection Drugs 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides mannitol and treat the purposes in the medicine of mammitis of cow with enrofloxacin drug combination in preparation. Present invention also offers a kind of pharmaceutical composition treating mammitis of cow and its production and use. The mastitis of milch cow can effectively be treated by medicine of the present invention, quickly eliminates symptom, increases milk products yield and quality and steady quality, is suitable to clinical expansion.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition treating mammitis of cow.
Background technology
Mammitis of cow refers to that the breast of milch cow receives the factors such as physics, chemistry, microorganism and stimulates caused a kind of inflammatory diseases. The morbidity milk generation physicochemical property of milch cow, the change of cytology's character and mammary gland tissue generation Pathologic changes, cause milk yield to decline and milk quality reduces, and is one of four big diseases of harm dairy development. Extending milch cow post-partum estrus and pregnant time time serious, even make disease cattle lose production performance, cattle is dead and eliminates, and causes huge economic loss. Data at home and abroad shows, the morbidity number of various types of mammitis of cow especially latent mammitis accounts for the 1/3 of milk cow in lactation period sum, and mammitis of cow becomes one of current topmost disease affecting world's dairy development. In China, the annual expense nearly hundred million yuans for treating mammitis of cow, it can be seen that, the harm of dairy is huge by mastitis.
Quite ripe about the diagnostic techniques of the mastitis of milch cow and latent mammitis at present, but Therapeutic Method but compares shortcoming. The mastitis of milch cow is treated still to use antibacterials to coordinate anti-inflammation drugs in China, but owing to the existence of blood breast barrier and the inflammation of inflammatory breast tissue thicken, the medicine causing the mammary gland tissue of the medicine arrival inflammation by intramuscular injection and intravenous drip does not reach effective dosage, and effect is poor. In the selection for the treatment of bovine mastitis medicine, there is presently no the infusion solution being specifically designed to mammitis of cow, generally clinical veterinary personnel need to mix antibiotic with normal saline or glucose injection, due to antibiotic specification, to compare specification with milch cow dosage less, thus veterinary in the process of dilution not only trouble and also easily pollute.
Application number: 200580038478.2, denomination of invention: use the treatment of the mastitis of enrofloxacin, this patent relates to a kind of mastitis using enrofloxacin or ciprofloxacin and simplifies treatment, in particular for cow.
Summary of the invention
The technical scheme is that and provide a kind of pharmaceutical composition treating mammitis of cow, another technical scheme of the present invention there is provided preparation method and the purposes of this pharmaceutical composition.
The invention provides mannitol and treat the purposes in the medicine of mammitis of cow with enrofloxacin drug combination in preparation.
It is further preferred that the weight proportion of mannitol and enrofloxacin is:
Mannitol 20-25 part, enrofloxacin 0.2-0.4 part.
It is further preferred that the weight proportion of mannitol and enrofloxacin is:
20 parts of mannitol, enrofloxacin 0.2 part.
Medicine provided by the invention is with mannitol and enrofloxacin for active component, adds pharmaceutically acceptable adjuvant or preparation that complementary composition is prepared from.
Wherein, described complementary composition is vitamin C, sodium bicarbonate.
Wherein, described preparation is injection.
Being converted to percentage by weight, in drug injection of the present invention, the percentage composition of mannitol and enrofloxacin is respectively as follows: mannitol 20-25%, enrofloxacin 0.2-0.4%.
Present invention also offers a kind of pharmaceutical composition treating mammitis of cow, it is the preparation being prepared from by the crude drug of following weight proportioning:
Mannitol 20-25 part, enrofloxacin 0.2-0.4 part.
It is further preferred that it is the preparation being prepared from by the crude drug of following weight proportioning:
20 parts of mannitol, enrofloxacin 0.2 part.
Wherein, described preparation is injection.
Mannitol is 0.5-1.5% as the concentration of isoosmotic adjusting agent, in medicine of the present invention, the weight percentage of mannitol is 20-25%, is far longer than the concentration as osmotic pressure regulator, as functional competence material, increase the enrofloxacin drug level at mastitis cow breast, improve drug effect. Medicine of the present invention is the medicine aiming at milch cow design for mastitis treatment, not only easy to use, and reliable in quality curative effect is certain.
Detailed description of the invention
The preparation of embodiment 1 injection of the present invention
1, prescription
Mannitol 20g
Enrofloxacin 0.2g
Milch cow is administered according to enrofloxacin 2.5mg/kg body weight.
2, preparation technology
Taking mannitol appropriate, be dissolved in appropriate water for injection (50%), add the needle-use activated carbon of 0.3%, agitating heating is dissolved and is boiled 10min, filters with 0.45 micrometer Millipore filter membrane while hot, stand-by; Separately taking enrofloxacin appropriate, add appropriate water for injection stirring (20%), regulate pH with vitamin C and make enrofloxacin dissolve, 0.45 micrometer Millipore filter membrane filters, stand-by; Mannitol solution and enrofloxacin liquid being mixed, water for injection complements to full dose, regulates pH to 4.0-4.5 with vitamin C or sodium bicarbonate, with processing clean 500ml large transfusion bottle subpackage, and Zha Gai, 115 DEG C of autoclaving 30min and get final product.
The preparation of embodiment 2 injection of the present invention
Take mannitol 25g, enrofloxacin 0.4g, prepare into injection by the method for embodiment 1.
Embodiment 3 injection weight proportion screening test of the present invention
Being respectively configured mannitol enrofloxacin percentage ratio according to the preparation technology of embodiment 1 is: 20:0.2; 20:0.3; 20:0.4; 25:0.2; 25:0.3; 25:0.4 prescription drug, investigate its stability from character (appearance luster), content (determining enrofloxacin content), pH value, clarity respectively. Manufacture experimently above-mentioned test sample, commercially available back respectively, temperature 25 DEG C �� 2 DEG C, place 12 months when relative humidity 60% �� 10%. Sampling in every 3 months once, sampled respectively at 0 month, 3 months, 6 months, 9 months, 12 months, detects by stability high spot reviews project.
Experimental result: testing from long-time stability, the optimal proportion of this prescription enrofloxacin mannitol is 20:0.2, and under this proportioning, character, content, pH value, clarity all meet regulation.The ratio of enrofloxacin mannitol 25:0.2 is also more stable, but stable content does not have enrofloxacin, and mannitol 20:0.2 ratio is good. When mannitol reaches 25, it is possible to crystallization, but temperature bath can be dissolved, simply inconvenient when Clinical practice, but does not affect quality.
Beneficial effects of the present invention is proved below by way of pharmacological evaluation.
Test example 1 Drug therapy mammitis of cow of the present invention
1 experimental technique
Randomly selecting the clinical milch cow 6 that mastitis occurs, the criterion of mastitis milch cow is, Contents in Cows temperature rise, and breast redness is hardening, but lactiferous ducts is blocking, can extrude thin milk. Clean milk is first squeezed before experiment, then being classified as enrofloxacin group (commercially available enrofloxacin injection) and enrofloxacin mannitol medicine group (20:0.2, prepared by embodiment 1 method), wherein the content of enrofloxacin is 0.2%, it is administered according to 2.5mg/kg, intravenous drip respectively, instils after terminating in 1h, 3h, 5h respectively milks once, stay milk sample 10ml, 4 DEG C of preservations, take back the content of enrofloxacin and ciprofloxacin in experimental determination milk.
2 experimental results
| Packet | 1h (enrofloxacin/ciprofloxacin) | 3h (enrofloxacin/ciprofloxacin) | 5h (enrofloxacin/ciprofloxacin) |
| Enrofloxacin group | 0.32/0.07��g/ml | 1.65/0.45��g/ml | 1.17/0.23��g/ml |
| Enrofloxacin mannitol medicine group | 0.55/0.12��g/ml | 2.01/0.82��g/ml | 1.89/0.52��g/ml |
3 analyze discussion
Enrofloxacin can metabolism be ciprofloxacin after entering blood in liver, so should being detected together with ciprofloxacin by enrofloxacin when detection. From result, compound enrofloxacin mannitol medicine group milk drug concentration is apparently higher than enrofloxacin group, illustrate that mannitol is conducive to enrofloxacin to pass through blood breast barrier, owing to enrofloxacin is the antibacterials that concentration complies with resistance to type, therefore mannitol is conducive to the blood drug level that the maintenance of enrofloxacin blood drug level is higher.
Test example 2 clinical drug application test of the present invention
1 experimental technique
Choosing the milch cow 65 of cattle farm, Yaan clinic generation mastitis in 2013.5-2013.10, be divided into and be not administered group 18, enrofloxacin group 21 and compound enrofloxacin mannitol treatment group (20:0.2) 21, equal intravenous drip, treatment is once. Mastitis milch cow shows themselves in that the ziega that Contents in Cows temperature rise, udder edema, galactostasis or extrusion yellow are cotton-shaped, mastalgia. Two groups of milch cows, feeding and management keeps consistent.
Curative effect judging standard is: a cures, and temperature recovery is normal, and udder edema eliminates, and milk is normal milky; B is effective, and body temperature is close to normal, and edema alleviates, and can extrude milk, and color is close to normal; C is invalid, still shows as the ziega that fever, udder edema, galactostasis or extrusion yellow are cotton-shaped.
2 experimental results
| Packet | Cure | Effectively | Invalid |
| It is not administered group | 0% | 0% | 100% |
| Enrofloxacin group | 38.1% | 66.7% | 33.3% |
| Enrofloxacin mannitol group | 95.2% | 100% | 0 |
3 analyze discussion
From result, isodose enrofloxacin, the effect of compound enrofloxacin formula mannitol injection liquid is substantially owing to enrofloxacin is alone. Compound enrofloxacin formula mannitol injection liquid can improve cure rate 157.7%, and effective percentage improves 49.9%. Although compound enrofloxacin formula mannitol injection liquid improves breast concentration causes residual, but compound enrofloxacin formula mannitol injection liquid effectively shortens the course of disease of mastitis, reduce and abandon milk amount, increase economic efficiency, with alone enrofloxacin cause the course of disease extend increase to abandon milk amount comparative advantages obvious.
4 conclusions
Compound enrofloxacin formula mannitol injection liquid of the present invention can effectively treat the mastitis of milch cow, quickly eliminates symptom, increases milk products yield and quality, steady quality, is suitable to clinical expansion.
Claims (7)
1. mannitol and the enrofloxacin drug combination purposes in the medicine of preparation treatment mammitis of cow, wherein, the weight proportion of mannitol and enrofloxacin is:
20 parts of mannitol, enrofloxacin 0.2 part.
2. purposes according to claim 1, it is characterised in that: it is with mannitol and enrofloxacin for active component, adds the preparation that complementary composition is prepared from.
3. purposes according to claim 2, it is characterised in that: described complementary composition is vitamin C, sodium bicarbonate.
4. purposes according to claim 2, it is characterised in that: described preparation is injection.
5. the pharmaceutical composition treating mammitis of cow, it is characterised in that: its active component is the preparation being prepared from by the crude drug of following weight proportioning:
20 parts of mannitol, enrofloxacin 0.2 part.
6. pharmaceutical composition according to claim 5, it is characterised in that: described preparation is injection.
7. the method preparing pharmaceutical composition described in claim 5 or 6, it comprises the steps:
A, taking mannitol and be dissolved in water for injection, add needle-use activated carbon, agitating heating is dissolved and is boiled, while hot with 0.45 micrometer Millipore filter membrane filtration, stand-by;
B, separately take enrofloxacin, inject and blunge, regulate pH with vitamin C and make full dose 0.2-0.4% enrofloxacin dissolve, 0.45 micrometer Millipore filter membrane filtration, stand-by;
C, mannitol solution and enrofloxacin liquid being mixed, water for injection complements to full dose, then regulates pH to 4.0-4.5, subpackage, 115 DEG C of autoclavings with vitamin C or sodium bicarbonate, to obtain final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410239009.8A CN103977006B (en) | 2014-05-30 | 2014-05-30 | A kind of pharmaceutical composition treating mammitis of cow and its production and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410239009.8A CN103977006B (en) | 2014-05-30 | 2014-05-30 | A kind of pharmaceutical composition treating mammitis of cow and its production and use |
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| Publication Number | Publication Date |
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| CN103977006A CN103977006A (en) | 2014-08-13 |
| CN103977006B true CN103977006B (en) | 2016-06-08 |
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| CN201410239009.8A Expired - Fee Related CN103977006B (en) | 2014-05-30 | 2014-05-30 | A kind of pharmaceutical composition treating mammitis of cow and its production and use |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106511445A (en) * | 2016-12-30 | 2017-03-22 | 成都乾坤动物药业股份有限公司 | Application of pithecellobium clypearia or extract to preparation of drugs for treating cow mastitis |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1115641A (en) * | 1995-07-06 | 1996-01-31 | 东北制药总厂 | Prepn of cyclopropyloxacini injecta |
| CN101912359A (en) * | 2010-06-02 | 2010-12-15 | 广州天王动物保健品有限公司 | Enrofloxacin injection |
| CN102204884A (en) * | 2011-04-06 | 2011-10-05 | 广东如来医药进出口有限公司 | Composition preparation of ofloxacin compound and mannitol, and preparation method thereof |
-
2014
- 2014-05-30 CN CN201410239009.8A patent/CN103977006B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1115641A (en) * | 1995-07-06 | 1996-01-31 | 东北制药总厂 | Prepn of cyclopropyloxacini injecta |
| CN101912359A (en) * | 2010-06-02 | 2010-12-15 | 广州天王动物保健品有限公司 | Enrofloxacin injection |
| CN102204884A (en) * | 2011-04-06 | 2011-10-05 | 广东如来医药进出口有限公司 | Composition preparation of ofloxacin compound and mannitol, and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 司帕沙星注射液的研制及质量控制;李航 等;《中国药业》;20020930;第11卷(第9期);第51页左栏 * |
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Address after: 611130 Wenjiang City, Chengdu Province, Chengdu cross strait science and Technology Industrial Park Road, No. 259 Jin Fu Road, No. Patentee after: Chengdu Qiankun animal pharmaceutical Limited by Share Ltd Address before: 611130 Wenjiang, Chengdu, Chengdu cross strait science and Technology Industrial Development Zone, Jin Fu Road, Sichuan Patentee before: Chengdu Qiankun Animal Pharmaceutical Co.,Ltd. |
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Granted publication date: 20160608 Termination date: 20190530 |