CN101822688B - Compound tylosin injection for animals and preparation method thereof - Google Patents
Compound tylosin injection for animals and preparation method thereof Download PDFInfo
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- CN101822688B CN101822688B CN2010101764071A CN201010176407A CN101822688B CN 101822688 B CN101822688 B CN 101822688B CN 2010101764071 A CN2010101764071 A CN 2010101764071A CN 201010176407 A CN201010176407 A CN 201010176407A CN 101822688 B CN101822688 B CN 101822688B
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- injection
- tylosin
- animals
- compound
- trimethoprim
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- 239000004182 Tylosin Substances 0.000 title claims abstract description 66
- 229930194936 Tylosin Natural products 0.000 title claims abstract description 66
- WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 title claims abstract description 66
- 235000019375 tylosin Nutrition 0.000 title claims abstract description 66
- 229960004059 tylosin Drugs 0.000 title claims abstract description 66
- 238000002347 injection Methods 0.000 title claims abstract description 55
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- 241001465754 Metazoa Species 0.000 title claims abstract description 41
- 150000001875 compounds Chemical class 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title abstract description 13
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229960001082 trimethoprim Drugs 0.000 claims abstract description 29
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- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 claims abstract description 26
- PTNZGHXUZDHMIQ-UHFFFAOYSA-N 4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2C(C)C(C(O)C3C(C(O)=C(C(N)=O)C(=O)C3N(C)C)(O)C3=O)C3=C(O)C2=C1O PTNZGHXUZDHMIQ-UHFFFAOYSA-N 0.000 claims abstract description 24
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- PLCQGRYPOISRTQ-FCJDYXGNSA-L dexamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-FCJDYXGNSA-L 0.000 claims abstract description 21
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- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 13
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to compound tylosin injection for animals and a preparation method thereof. The injection consists of tylosin, doxycycline hydrochloride, trimethoprim, aminophylline, dexamethasone sodium phosphate, organic solvent and injection water. As a dedicated compound preparation for animals, the injection has special effect for treating respiratory tract infection caused by livestock and poultry sensitive bacteria and mycoplasmosis of pigs and poultry. The method has the advantages of convenient use, short course of treatment, low drug resistance and the like.
Description
Technical field
The present invention relates to a kind of compound tylosin injection for animals, particularly a kind of injection of processing by tylosin, doxycycline hydrochloride, trimethoprim, aminophylline, dexamethasone sodium phosphate and preparation method thereof.
Background technology
Tylosin (Enrofloxacin); It is the representative of QNS of new generation; Be designated as the animal specific medicine; The various infection that various bacteria is caused have significant curative effect, particularly the lethality of various Mycoplasmas are significantly higher than the quinolones other medicines and medicines such as mycin are herded by various for many years tylosin, the Thailand of having used, wide spectrum, efficient, low toxicity, good, the convenient drug administration of absorption.MIC to most of bacterial strains all is lower than 1 μ g/ml, and sensitive organism is had tangible antibiotic after effect (PAE).Be applicable to the sensitive bacterial of cattle, pig, fowl, dog, cat and aquatic animal and the various infectious disease of the digestive system due to the mycoplasma, respiratory system, urinary system and skin soft tissue, be mainly used in mycoplasma, Bacillus pasteurii disease, haemophilus, colibacillosis, Salmonella, streptococcicosis etc.Particularly have aspect the pig that causes of treatment haemophilus, the avian disease rapid-action, the characteristics that curative effect is high.
Doxycycline hydrochloride (Doxycycline Hyclate) belongs to Tetracyclines broad ectrum antibiotic class; Stronger to gram positive bacteria effects such as staphylococcus, Hemolytic streptococcus, anthrax bacillus, clostridium tetani and clostridium, responsive to gram negative bacterias such as escherichia coli, Salmonella, brucella and pasteurellosis bacilluss.External and the equal oxytetracycline of antibacterial activity in vivo, tetracycline are strong, clinical mycoplasma, colibacillosis, salmonellosis, Bacillus pasteurii disease and the psittacosis etc. that are mainly used in the treatment poultry.Its metabolic way: part is in the form deactivation of enteral with chelating, and dog has 75% dosage to eliminate with this kind mode.Renal excretion is only about 25%, and bile excretion is less than 5%, and its toxicity is minimum in poisoning by tetracycline group antibiotic property, but arrhythmia, collapse and dead report occur after the equus intravenous injection is arranged.
Aminophylline (Aminophylline) has direct relexation to bronchial smooth muscle.Its mechanism of action is to suppress phosphodiesterase, makes the hydrolysis rate of cAMP slack-off, and cAMP/cGMP ratio in the tissue that raises suppresses the release that histamine and slow reacting substance waited sensitive media, promotes catecholamine to discharge, and makes bronchial smooth muscle lax; The directly effect of a lax bronchial smooth muscle in addition simultaneously, thus bronchial muscular spasm removed, alleviate the congestion and edema of bronchial mucosa, bring into play the effect of relievining asthma.In addition, these article also have more weak heart tonifying and diuresis.Be mainly used in and alleviate the bronchial asthma symptom, also be used for the trouble poultry of cardiac insufficiency or pulmonary edema.
Synergistic factor is selected trimethoprim (Trimethoprim) for use (TMP); Has a broad antifungal spectrum; Multiple gram positive bacteria and negative bacterium are all had antibacterial action, and its mechanism of action is to suppress dihydrofolate reductase, makes dihydrofoilic acid can not be reduced into tetrahydrofolic acid; Thereby block responsive folic acid metabolism and utilization, thereby overslaugh thalline nucleic acid is synthetic.Single with being prone to cause bacterial drug resistance; So many and sulphonamides, Tri-Biocin, Du-6859a coupling can strengthen drug effect and reach several times to tens times, even bactericidal action occur; And can reduce the generation of Resistant strain, there is chemical sproof bacterial strain also can suppress to sulphonamides.Trimethoprim injection post-absorption is rapid; Can reach effective Mlc in the medication 2-3 hour blood, be distributed widely in each tissue and the body fluid, the concentration in liver, kidney, lung, skin can surpass blood level; It is more in the acid medium tissue, to distribute; Trimethoprim is mainly discharged from kidney, in aciduria, discharges and increases, and rushes down from milk, bile row on a small quantity.Be used for respiratory tract, digestive tract, urogenital infections.
Dexamethasone sodium phosphate (Dexamethasone Sodium Phosphate) belongs to the glucocorticoids medicine; Have tangible pharmacological action, comprise antiinflammatory, antiallergic, antitoxin, shock, influence metabolism etc., be usually used in serious infectious disease, anaphylactic disease, shock, local inflammation, milch cow ketonemia and sheep pregnancy induced hypertension syndrome; Induced labor and prevention operation sequela; The application of its effect is similar with hydrocortisone, but effect is stronger, and effective time is long; Side effect is less; Antiinflammatory action and glyconeogenesis are 25 times of hydrocortisone, and water receives retention and excretory effect and be merely 3/4 of hydrocortisone, and be stronger to the inhibitory action of hypophysis-adrenal cortex axle.
Injection means that the confession that medicine is processed injects intravital sterile solution, emulsion or suspension, and supplies to face sterilized powder or the concentrated solution with preceding wiring solution-forming or suspension.The characteristics of injection mainly show route of administration crossing digestive system with defence tissue (liver) and directly inject tissue or blood vessel, so drug effect are rapid, is applicable to first aid.But also the curative effect of some injection is long, to adapt to the needs in the medical treatment.The dosage of injection is accurate, and reliable effect possibly suffer the influence of Digestive system, food etc. unlike the endo-medicine that kind, and curative effect can not take place the dosage that uses fully.In addition, can make some drugs bring into play localized effect again.
Summary of the invention
The present invention is directed to the deficiency of prior art, a kind of compound tylosin injection for animals and preparation method thereof is provided.
The present invention becomes compound preparation with tylosin, doxycycline hydrochloride, trimethoprim, aminophylline, dexamethasone sodium phosphate compatibility; Be used to treat pig, fowl mycoplasma; Like mycoplasma pneumonia and the mycoplasmal arthritis of chronic respiratory disease of fowl (CRD) and infectiousness hole chamber inflammation and pig, the mycoplasma infection concurrent to sensitive organism has specially good effect.Also be used to treat the microbial pulmonis Bovis seu Bubali inflammation of cattle pasteurellaceae, hyopneumoniae etc.Be prone to after the animal intramuscular injection absorb, long action time, local irriate effect is little, treating both the principal and secondary aspects of a disease, and also easy to use, short treating period, drug resistance is low.
Technical scheme of the present invention is following:
A kind of compound tylosin injection for animals, component is following, is weight portion:
Tylosin 5～20, doxycycline hydrochloride 3～10, magnesium chloride 1.41～3.3, sodium formaldehyde sulphoxylate 0.1～0.5; Sodium thiosulfate 0.1～0.2, trimethoprim 2～4, aminophylline 3～6; Dexamethasone sodium phosphate 0.02～0.15, organic solvent 50～70, water for injection 10～30;
Described organic solvent is alpha-pyrrolidone, N, dinethylformamide and propylene glycol, and alpha-pyrrolidone, N, the weight ratio of dinethylformamide and propylene glycol is (2～5): (1～2): (1～2).
Preferably, component is following, is weight portion:
Tylosin 10, doxycycline hydrochloride 5, trimethoprim 3.75, aminophylline 4, dexamethasone sodium phosphate 0.05; Magnesium chloride 2.35, sodium formaldehyde sulphoxylate 0.25, sodium thiosulfate 0.15, alpha-pyrrolidone 30; N, dinethylformamide 15, propylene glycol 15, water for injection 20.
The method for preparing of above-mentioned compound tylosin injection for animals, step is following:
1) magnesium chloride is dissolved in water for injection after, add alpha-pyrrolidone, add doxycycline hydrochloride again, stirring and dissolving, doxycycline hydrochloride solution;
2) sodium formaldehyde sulphoxylate is dissolved in water for injection after, join in the doxycycline hydrochloride solution that step 1) makes, add again after ethanolamine stirs, add tylosin again, stir and make dissolving, the tylosin mixed solution;
3) trimethoprim is dissolved in N, behind the dinethylformamide, joins step 2) in the tylosin mixed solution that makes, the trimethoprim mixed solution;
4) dexamethasone sodium phosphate is dissolved in the water for injection, gets dexamethasone sodium phosphate solution;
5) aminophylline is dissolved in the water for injection, gets aminophylline solution;
6) sodium thiosulfate is dissolved in the water for injection, gets hypo solution;
7) the dexamethasone sodium phosphate solution that step 4) is made, the aminophylline solution that step 5) makes, the hypo solution that step 6) makes stir respectively and join in the trimethoprim mixed solution that step 3) makes; Add propylene glycol again; Stir; After the water for injection titration,, must filtrate with organic membrane filtration of 0.22～0.45um;
8) filtrating that step 7) is made promptly gets compound tylosin injection for animals 121 ℃, 0.15mpa sterilization 15～20 minutes.
Preferably, N in alpha-pyrrolidone, the step 3) in the said step 1), the weight ratio of propylene glycol is (2～5) in dinethylformamide and the step 7): (1～2): (1～2).
Preferably, in the said step 7), after the water for injection titration, also comprise and transfer pH to 8.5～9.0.
Further preferred, transferring the pH regulator agent in pH to 8.5～9.0 is ethanolamine solutions.PH value is regulated and can be operated by state of the art.
More than each raw material components be medical commercially available prod.
Technique effect of the present invention is following:
1, tylosin is the animal specific medicine, and it not only has, and wide spectrum, efficient, low toxicity, absorption are good, the characteristics of convenient drug administration, and the infection that various bacteria causes is had significant curative effect.Be applicable to the sensitive bacterial of cattle, pig, fowl, dog, cat and aquatic animal and the various infectious disease of the digestive system due to the mycoplasma, respiratory system, urinary system and skin soft tissue, be mainly used in treatment mycoplasma, Bacillus pasteurii disease, haemophilus, colibacillosis, Salmonella, streptococcicosis etc.The haemophilus disease of particularly treating pig that haemophilus causes, fowl is rapid-action, and curative effect is high.Sulfamethoxazole is a kind of broad-spectrum antibacterial agent; All effective to most gram positive bacterias and part gram negative bacteria; Concentration in blood is held time longer, is used to treat the systemic infection due to the various animal sensitive organisms, is pneumonia, the bronchitic choice drug that the treatment haemophilus causes.Tylosin be the macrolide apoplexy due to endogenous wind to one of the strongest medicine of mycoplasma effect, be mainly used in control pig, fowl mycoplasma, like the mycoplasma pneumonia of chronic respiratory disease of fowl (CRD) and infectiousness hole chamber inflammation and pig and mycoplasmal arthritis etc.Antimicrobial spectrum has promptly been widened in three's combination, has strengthened the targeting to haemophilus again, treating both the principal and secondary aspects of a disease, and a pin takes effect.
2, add trimethoprim (TMP), make tylosin, doxycycline hydrochloride antibacterial action strengthen several times to tens times.
3, add glucocorticosteroid hormone drug dexamethasone sodium phosphate and anti-asthmatic aminophylline, can remove surface symptoms rapidly.
4, injection pH value 8.5-9.0 according to the invention can satisfy the adaptability requirement of body, quickens the absorption of body tissue to medicine, reduces local excitation, can keep the stability and the maximum antibacterial activity of medicinal liquid again, ensures the quality of products, and guarantees curative effect.
The specific embodiment
Below in conjunction with embodiment technical scheme of the present invention is explained in detail, but protection domain is not limited thereto.
Each raw material explanation is as follows among the embodiment: tylosin (Tylosin), and Ningxia Duoweitairui Pharmaceutical Co., Ltd sells; Doxycycline hydrochloride, Handan roc of a specified duration pharmaceutcal corporation, Ltd sells; Aminophylline, Shouguang Fukang Pharmaceutical Co., Ltd. sells; Trimethoprim (Trimethoprim, TMP), sell by the holy nation in Shouguang City bio tech ltd.Magnesium chloride, sodium formaldehyde sulphoxylate, sodium thiosulfate, dexamethasone sodium phosphate, alpha-pyrrolidone, N, dinethylformamide and propylene glycol are medical commercially available prod.
The test method of compound tylosin injection for animals:
The test data of this compound tylosin injection for animals is following: controlled animal by the body weight administration, and compound tylosin injection for animals of injection in first day, injection volume is 0.1ml/kg; Used the administration of medicine drinking-water in second day instead; Continue treatment three days, the preparation of medicine drinking-water is to get compound tylosin injection for animals 100ml, converts water 100kg; The dosage of every kilogram of (the weight of animals) 0.1ml compound tylosin injection supplies animal pharmaceuticals drinking-water by every day, detects by conventional method then.
Embodiment 1
A kind of compound tylosin injection for animals, component is following:
Tylosin 10g, doxycycline hydrochloride 5g, trimethoprim 3.75g, aminophylline 4g, dexamethasone sodium phosphate 0.05g; Magnesium chloride 2.35g, sodium formaldehyde sulphoxylate 0.25g, sodium thiosulfate 0.15g, alpha-pyrrolidone 30g; N, dinethylformamide 15g, propylene glycol 15g, water for injection 20g.
Above-mentioned compound tylosin injection for animals adopts the following steps preparation:
1) magnesium chloride 2.35g is dissolved in water for injection 3g after, add alpha-pyrrolidone 30g, add doxycycline hydrochloride 5g again, stirring and dissolving, doxycycline hydrochloride solution;
2) sodium formaldehyde sulphoxylate 0.25g is dissolved in water for injection 3g after, join in the solution that step 1) makes, add again after the 2g ethanolamine stirs, add tylosin 10g again, stir and make dissolving, the tylosin mixed solution;
3) use N, behind the dinethylformamide 15g dissolving trimethoprim 3.75g, join step 2) in the tylosin solution that makes, the trimethoprim mixed solution;
4) dexamethasone sodium phosphate 0.05g is dissolved in the 3g water for injection, gets dexamethasone sodium phosphate solution;
5) aminophylline 4g is dissolved in the 10g water for injection, gets aminophylline solution
6) sodium thiosulfate is dissolved in the 1g water for injection, gets hypo solution;
7) the dexamethasone sodium phosphate solution that step 4) is made, the aminophylline solution that step 5) makes, the hypo solution that step 6) makes stir and join in the trimethoprim mixed solution that step 3) makes; Add the 15g propylene glycol again; Stir, after the water for injection titration, ethanolamine solutions adjust pH to 8.7; With organic membrane filtration of 0.25um, must filtrate;
8) filtrating that step 7) is made promptly gets compound tylosin injection for animals 121 ℃, 0.15mpa sterilization 20 minutes.
The present embodiment clinical therapeutic efficacy is following:
Table 1 compound tylosin injection clinical therapeutic efficacy
| Animal | Name of disease | The case sum | Total number of curing | Average cure rate % |
| Pig | Asthma | 323 | 309 | 95.67％ |
| Cattle | Pneumonia | 92 | 90 | 97.82％ |
Table 2 the present invention and tylosin injection clinical treatment comparative test result
Concrete case:
Han Dian town, Zouping County Zhang raises 400 of pigs, and sudden onset shows as tangible dyspnea, opens one's mouth to breathe; Sagging, a corner or crouch down on ground of standing is the dog sitting posture sometimes; Cut open inspection through pathology, find that the lung of dead pig has in various degree edema and edema due to disorder of QI, confluent bronchopneumonia occurs at lobus cardiacus, sharp leaf, middle leaf; Be meat appearance or liver appearance pathological changes, the most remarkable with lobus cardiacus, comprehensive diagnos is a swine enzootic pneumonia.Use injection for treating of the present invention, after the injection once, asthma symptom obviously alleviates, and continues treatment, after three days, and basic rehabilitation, cure rate reaches 95.64%.
Safety testing result: the no abnormal death of the injection sick pig in back.Observed 30 days, the trouble poultry after the administration grows fine, and does not have any disease dead 2 of matched group takes place.
Show through above experiment; Injection of the present invention is treated in clinical and is mainly used in control pig, fowl mycoplasma; Like mycoplasma pneumonia and the mycoplasmal arthritis of chronic respiratory disease of fowl (CRD) and infectiousness hole chamber inflammation and pig, the mycoplasma infection concurrent to sensitive organism has specially good effect.Also be used to treat the microbial pulmonis Bovis seu Bubali inflammation of cattle pasteurellaceae, hyopneumoniae etc.Be prone to after the animal intramuscular injection absorb, long action time, local irriate effect is little, treating both the principal and secondary aspects of a disease, and also easy to use, short treating period, drug resistance is low.
Contrast therapy result shows that injection for treating of the present invention is 95.62% to the cure rate of swine enzootic pneumonia, is higher than matched group, is superior to the tylosin injection group.
Safety test proves that the present invention does not show toxic and side effects.
The stability test of product:
Stability testing method: compound tylosin injection for animals (10ml normal injection ampoule bottle splendid attire) places calorstat (38 ℃～42 ℃ of temperature; Humidity 70%～80%) accelerated test three months under the condition; When producing, deposit one month, deposited two months and deposited each sampling in three months once, its character, pH value, content are detected.
The stability test result: all kinds of indexs of product, see following table for details.
| Holding time | Character | PH value | Tylosin content (labelled amount %) | Doxycycline hydrochloride (labelled amount %) | Trimethoprim content (labelled amount %) | Aminophylline content (labelled amount %) | Content determination of Dexamethasone Sodium (labelled amount %) |
| 0 month | Faint yellow to yellow clear liquid | 8.3 | 101.2 | 100.1 | 99.7 | 99.8 | 100.1 |
| 1 month | Faint yellow to yellow clear liquid | 8.3 | 100.2 | 98.9 | 98.7 | 99.8 | 98.2 |
| 2 months | Faint yellow to yellow clear liquid | 8.3 | 97.2 | 99.8 | 97.2 | 97.2 | 97.5 |
| 3 months | Faint yellow to yellow clear liquid | 8.3 | 94.2 | 95.4 | 95.7 | 95.0 | 95.8 |
Can find out from above data; After through 3 months product accelerated test; Product colour does not have significant change, and all within prescribed limit, pH does not have significant change; Within prescribed limit, meeting national veterinary drug standard active ingredient after the product active constituent content changes is the regulation in labelled amount 90%～110% scope.The result shows, 38 ℃～42 ℃ of temperature, under the condition of humidity 70%～80%, pH value is between 8.5～9.0 the time, and character, pH value, content are all up to specification, explain that these article are very stable under this experimental condition.Under conventional condition of storage, can preserve 2 years.
Embodiment 2
A kind of compound tylosin injection for animals, component is following:
Tylosin 5g, doxycycline hydrochloride 3g, Shen oxygen benzyl pyridine 2g, aminophylline 3g; Dexamethasone sodium phosphate 0.02g, magnesium chloride 1.41g, sodium formaldehyde sulphoxylate 0.1g, sodium thiosulfate 0.1g; Alpha-pyrrolidone 20g, N, dinethylformamide 20g, propylene glycol 20g; Water for injection 30g;
Preparation process gets compound tylosin injection for animals with embodiment 1, and pH is 8.5.
The present embodiment clinical therapeutic efficacy is following:
Table 1 compound tylosin injection clinical therapeutic efficacy
| Animal | Name of disease | The case sum | Total number of curing | Average cure rate % |
| Pig | Asthma | 351 | 333 | 94.87％ |
| Cattle | Pneumonia | 89 | 86 | 96.63％ |
Table 2 the present invention and tylosin injection clinical treatment comparative test result
The stability test of product is with embodiment 1.
| Holding time | Character | The pH value | Tylosin content (labelled amount %) | Doxycycline hydrochloride (labelled amount %) | Trimethoprim content (labelled amount %) | Aminophylline content (labelled amount %) | Content determination of Dexamethasone Sodium (labelled amount %) |
| 0 month | Faint yellow to yellow clear liquid | 8.5 | 101.2 | 100.1 | 99.7 | 99.8 | 100.1 |
| 1 month | Faint yellow to yellow clear liquid | 8.5 | 101.2 | 100.1 | 99.7 | 99.8 | 100.1 |
| 2 months | Faint yellow to yellow clear liquid | 8.5 | 101.1 | 100.0 | 99.5 | 99.7 | 100.0 |
| 3 months | Faint yellow to yellow clear liquid | 8.5 | 101.1 | 100.0 | 99.5 | 99.7 | 100.0 |
Can find out from above data; After through 3 months product accelerated test; Product colour does not have significant change, and all within prescribed limit, pH does not have significant change; Within prescribed limit, meeting national veterinary drug standard active ingredient after the product active constituent content changes is the regulation in labelled amount 90%～110% scope.The result shows, 38 ℃～42 ℃ of temperature, under the condition of humidity 70%～80%, pH value is between 8.5～9.0 the time, and character, pH value, content are all up to specification, explain that these article are very stable under this experimental condition.Under conventional condition of storage, can preserve 2 years.
Embodiment 3
A kind of compound tylosin injection for animals, component is following:
Tylosin 15g, doxycycline hydrochloride 7g, trimethoprim 3g, aminophylline 3g; Dexamethasone sodium phosphate 0.1g, magnesium chloride 3.3g, sodium formaldehyde sulphoxylate 0.25g, sodium thiosulfate 0.15g; Alpha-pyrrolidone 40g, N, dinethylformamide 15g, propylene glycol 15g; Water for injection 20g;
Preparation process gets compound tylosin injection for animals with embodiment 1, and pH is 8.7.
The present embodiment clinical therapeutic efficacy is following:
Table 1 compound tylosin injection clinical therapeutic efficacy
| Animal | Name of disease | The case sum | Total number of curing | Average cure rate % |
| Pig | Asthma | 337 | 317 | 94.07％ |
| Cattle | Pneumonia | 89 | 85 | 95.51％ |
Table 2 the present invention and tylosin injection clinical treatment comparative test result
The stability test of product is with embodiment 1.
| Character | The pH value | Tylosin content (labelled amount %) | Doxycycline hydrochloride (labelled amount %) | Trimethoprim content (labelled amount %) | Aminophylline content (labelled amount %) | Content determination of Dexamethasone Sodium (labelled amount %) | |
| 0 month | Faint yellow to yellow clear liquid | 8.7 | 101.1 | 100.2 | 99.8 | 99.9 | 100.2 |
| 1 month | Faint yellow to yellow clear liquid | 8.7 | 101.1 | 100.2 | 99.8 | 99.9 | 100.2 |
| 2 months | Faint yellow to yellow clear liquid | 8.7 | 101.1 | 100.1 | 99.8 | 99.9 | 100.2 |
| 3 months | Faint yellow to yellow clear liquid | 8.7 | 101.0 | 100.1 | 99.7 | 99.8 | 100.1 |
Can find out from above data; After through 3 months product accelerated test; Product colour does not have significant change, and all within prescribed limit, pH does not have significant change; Within prescribed limit, meeting national veterinary drug standard active ingredient after the product active constituent content changes is the regulation in labelled amount 90%～110% scope.The result shows, 38 ℃～42 ℃ of temperature, under the condition of humidity 70%～80%, pH value is between 8.5～9.0 the time, and character, pH value, content are all up to specification, explain that these article are very stable under this experimental condition.Under conventional condition of storage, can preserve 2 years.
Embodiment 4
A kind of compound tylosin injection for animals, component is following:
Tylosin 20g, doxycycline hydrochloride 10g, trimethoprim 3.5g, aminophylline 4g; Dexamethasone sodium phosphate 0.15g, magnesium chloride 5.7g, sodium formaldehyde sulphoxylate 0.4g, sodium thiosulfate 0.15g; Alpha-pyrrolidone 50g, N, dinethylformamide 10g, propylene glycol 10g; Water for injection 15g;
Preparation process gets compound tylosin injection for animals with embodiment 1, and pH is 8.9.
The present embodiment clinical therapeutic efficacy is following:
Table 1 compound tylosin injection clinical therapeutic efficacy
| Animal | Name of disease | The case sum | Total number of curing | Average cure rate % |
| Pig | Asthma | 354 | 331 | 93.50％ |
| Cattle | Pneumonia | 98 | 92 | 93.88％ |
Table 2 the present invention and tylosin injection clinical treatment comparative test result
The stability test of product is with embodiment 1.
| Holding time | Character | PH value | Tylosin content (labelled amount %) | Doxycycline hydrochloride (labelled amount %) | Trimethoprim content (labelled amount %) | Aminophylline content (labelled amount %) | Content determination of Dexamethasone Sodium (labelled amount %) |
| 0 month | Faint yellow to yellow clear liquid | 8.9 | 101.2 | 100.2 | 99.7 | 99.8 | 100.1 |
| 1 month | Faint yellow to yellow clear liquid | 8.9 | 101.2 | 100.2 | 99.7 | 99.8 | 100.1 |
| 2 months | Faint yellow to yellow clear liquid | 8.9 | 101.0 | 100.2 | 99.6 | 99.7 | 100.0 |
| 3 months | Faint yellow to yellow clear liquid | 8.9 | 101.0 | 100.1 | 99.6 | 99.7 | 100.0 |
Can find out from above data; After through 3 months product accelerated test; Product colour does not have significant change, and all within prescribed limit, pH does not have significant change; Within prescribed limit, meeting national veterinary drug standard active ingredient after the product active constituent content changes is the regulation in labelled amount 90%～110% scope.The result shows, 38 ℃～42 ℃ of temperature, under the condition of humidity 70%～80%, pH value is between 8.5～9.0 the time, and character, pH value, content are all up to specification, explain that these article are very stable under this experimental condition.Under conventional condition of storage, can preserve 2 years.
Embodiment 5
A kind of compound tylosin injection for animals, component is following, is weight portion:
Tylosin 10g, doxycycline hydrochloride 10g, trimethoprim 4g, aminophylline 2.5g; Dexamethasone sodium phosphate 0.1g, magnesium chloride 5.7g, sodium formaldehyde sulphoxylate 0.5g, sodium thiosulfate 0.2g; Alpha-pyrrolidone 30g, N, dinethylformamide 25g, propylene glycol 25g; Water for injection 10g;
Preparation process gets compound tylosin injection for animals with embodiment 1, and pH is 9.0.
The present embodiment clinical therapeutic efficacy is following:
Table 1 compound tylosin injection clinical therapeutic efficacy
| Animal | Name of disease | The case sum | Total number of curing | Average cure rate % |
| Pig | Asthma | 316 | 291 | 92.09％ |
| Cattle | Pneumonia | 85 | 79 | 92.94％ |
Table 2 the present invention and tylosin injection clinical treatment comparative test result
The stability test of product is with embodiment 1.
| Holding time | Character | PH value | Tylosin content (labelled amount %) | Doxycycline hydrochloride (labelled amount %) | Trimethoprim content (labelled amount %) | Aminophylline content (labelled amount %) | Content determination of Dexamethasone Sodium (labelled amount %) |
| 0 month | Faint yellow to yellow clear liquid | 9.1 | 101.1 | 100.0 | 99.8 | 99.8 | 100.1 |
| 1 month | Faint yellow to yellow clear liquid | 9.1 | 99.8 | 98.6 | 99.3 | 99.5 | 99.7 |
| 2 months | Faint yellow to yellow clear liquid | 9.1 | 99.6 | 99.5 | 99.1 | 99.3 | 99.2 |
| 3 months | Faint yellow to yellow clear liquid | 9.1 | 99.4 | 98.2 | 99.0 | 99.2 | 99.1 |
Can find out from above data; After through 3 months product accelerated test; Product colour does not have significant change, and all within prescribed limit, pH does not have significant change; Within prescribed limit, meeting national veterinary drug standard active ingredient after the product active constituent content changes is the regulation in labelled amount 90%～110% scope.The result shows, 38 ℃～42 ℃ of temperature, under the condition of humidity 70%～80%, pH value is between 8.5～9.0 the time, and character, pH value, content are all up to specification, explain that these article are very stable under this experimental condition.Under conventional condition of storage, can preserve 2 years.
Claims (1)
1. a compound tylosin injection for animals is characterized in that component is following, is weight portion:
Tylosin 10, doxycycline hydrochloride 5, trimethoprim 3.75, aminophylline 4, dexamethasone sodium phosphate 0.05; Magnesium chloride 2.35, sodium formaldehyde sulphoxylate 0.25, sodium thiosulfate 0.15, alpha-pyrrolidone 30; N, dinethylformamide 15, propylene glycol 15, water for injection 20.
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| CN103405466B (en) * | 2012-08-06 | 2015-01-21 | 重庆金邦动物药业有限公司 | Compound synergistic tylosin tartrate |
| CN103405464B (en) * | 2012-08-06 | 2015-04-22 | 四川德润通生物科技有限公司 | Medicine for treating respiratory system infection of livestock and poultry |
| CN103432150B (en) * | 2012-08-06 | 2015-12-09 | 四川联美生物药业有限公司 | The compound medicine of potentiation tylosin tartrate soluble powder |
| CN102784158B (en) * | 2012-08-06 | 2013-08-21 | 四川德润通生物科技有限公司 | Preparation method of compound synergy tylosin tartrate for veterinary injection |
| CN103432151A (en) * | 2012-08-06 | 2013-12-11 | 重庆金邦动物药业有限公司 | Preparation method for compound synergistic tylosin tartrate |
| CN103405463A (en) * | 2012-08-06 | 2013-11-27 | 四川联美生物药业有限公司 | Preparation method of synergistic tylosin tartrate soluble powder compound medicine |
| CN108403700A (en) * | 2018-06-12 | 2018-08-17 | 新疆生产建设兵团第师畜牧兽医工作站 | A kind of cattle respiratory disease treatment composite injection |
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| CN101822688A (en) | 2010-09-08 |
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Assignee: Shandong Enkang Pharmaceutical Co., Ltd. Assignor: Chen Jianbo Contract record no.: 2011370000380 Denomination of invention: Compound tylosin injection for animals and preparation method thereof License type: Exclusive License Open date: 20100908 Record date: 20110822 |
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Granted publication date: 20120111 Termination date: 20210519 |