CN85101456A - Preparation method with new drug regimen of cooperative effect - Google Patents
Preparation method with new drug regimen of cooperative effect Download PDFInfo
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- CN85101456A CN85101456A CN85101456.9A CN85101456A CN85101456A CN 85101456 A CN85101456 A CN 85101456A CN 85101456 A CN85101456 A CN 85101456A CN 85101456 A CN85101456 A CN 85101456A
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Abstract
The invention relates to the antibiotics combination drug with cooperative effect of respiratory tract, gastrointestinal system or urinary system infectious disease and the septicemia of treatment domestic animal.This combination drug is by hydrogen Fumaric acid tiamulin and aminoglycoside antibiotic or its salt that allows in pharmacy, mixes with 5: 1 to 1: 5 weight ratios.Active component goes up available carrier with the veterinary and mixes with 1: 1 to 1: 50 weight ratio, perhaps goes up the preparation that is mixed with after the available carrier dilution for oral or parenteral applications with the veterinary.
Description
The present invention is about having the preparation method of the new drug regimen of cooperative effect, the disease that is caused by protozoon and antibacterial (swine dysentery treponema bacterium, bacillus coli, pasteurella, Salmonella, mycoplasma) of cattle, calf, sheep, goat, pig, rabbit and poultry can be treated and prevent to the combination of this kind new medicine thing.
People know that the maximum economic loss of swinery and group of birds is caused by gastrointestinal system and respiratory tract disease.The appearance of loss is not only because mortality rate is high and ever-increasing medical expense, and because reactive Therapeutic Method.
Mycoplasma has play a part important for the dysfunction that causes respiratory system, but the inflammation that is caused by inferior pathogen (streptococcus, staphylococcus, pasteurella, bordetella) is also very important.
Alimentary disease is normally caused by the undue growth of the gram-negative pathogens in the digestive system, and in these pathogen, the most important thing is the intrusion of bacillus coli strain, this not only can cause diarrhoea and the edema disease of swinery, also can make group of birds suffer from septicemia.
Female beastly gynaecopathia quantity is also in sustainable growth on a large scale, and the asymptomatic dysfunction of breast often takes place especially.The hole adenitis mainly is by streptococcus, staphylococcus, and bacillus coli and rod-like stem are microbial.
By infection bacterial and the protozoon cause of disease, a large amount of is treats and prevents with antibiotics and their composition of medicine.
Because the expansion of the antibiotics range of choice just might reduce significantly by bacterial and protozoon cause of disease communicate illness.
And the widely-used generation that has caused drug-fast strain of antibiotics for this class bacterial strain, uses a kind of antibiotics just not play effect.In order to prevent drug-fast generation, antibiotics only uses usually at short notice, the reason that continuous increase expense that Here it is is produced more and more newer antibiotics.
Hydrogen Fumaric acid tiamulin (14-deoxidation-14-((2-diethyl-amino-ethyl)-sulfhydryl-acetoxy group)-Mo clear the fields of weeds Siberian cocklebur) (Tiamulin(14-desoxy-14-((2-diethyl-amino-ethyl)-mercapto-acetoxy)-mutilin hydrogen fumarate) aspect veterinary treatment a kind of quite new antibiotics.Have been found that this antibiotics is to resisting some gram-positive bacterium, mycoplasma and effective to most important treponema bacterium.
The swine dysentery treponema bacterium that oral tiamulin makes pig suffer from dysentery to meeting, (british patent specification 2,072, No. 012) and meeting caused that the mycoplasma hyopneumoniae of animal endemicity pneumonia (Taylor, DJ, IPVS meeting, Mexico, 1982) is extremely effective.
The existing people of applied in any combination of tiamulin and vermifuge (tetramisole, left-handed rice azoles, fenbendazole, parbendazole, piperazine, dichlorvos) did research.Investigation had also been done in the toxicity of this combination drug and the compatibility.Also there is not the combination drug of known tiamulin and antibiotics to occur up to now.
Purpose of the present invention is exactly the combination drug of the known antibiotics of preparation, and this combination drug except expense significantly reduces, has also embodied the independent effect of two kinds or more of components with cooperative mode.
Aminoglycoside antibiotic (streptomycin, neomycin, kanamycin, gentamycin, tobramycin, situation mycin, apramycin or the like) is used for the treatment of acute and chronic respiratory organ, gastrointestinal tract and the urodeum infection that gram negative bacteria, staphylococcus and corynebacterium pyogenes cause.And according to written material, aminoglycoside antibiotic is also effective to Gram-positive pathogenic bacteria (staphylococcus aureus, Staphylococcus albus, corynebacterium, gas bacillus, Salmonella, Bacillus proteus, Neisseria, pasteurella).
Streptomycin and neomycin are used alone or in combination and extensively are used for the treatment of various infectious disease aspect veterinary treatments.
Streptomycin separately or be mainly used in parenteral with the combination (Si Teliedipeng injection) of penicillin and treat respiratory tract disease.
The combination of neomycin and oxytetracycline is used for the treatment of mastitis, and the bottled intrauterine of preparing against in capsule uses.
Parenteral uses neomycin because therefore its nephrotoxicity will be restricted, but also may cause azotemia and oliguria (German medical science weekly, 104,1783-1787/1979/) (Deutsche Med.Wschr.104,1783-1787/1979/)
Kanamycin separately or with the combination of procaine-penicillin, dihydrostreptomycin, neomycin mainly be do parenteral use (intramuscular, vein, subcutaneous, intrauterine or
In).
The main effective range of tobramycin and Togoplus is to act on Gram-negative pathogen (bacillus coli, Bacillus proteus, klebsiella, pseudomonas).These two kinds of antibiotics not only can be oral but also can have been made parenteral and use.
Apramycin is to the opposing coliform diarrhea, edema disease, dysentery (the antimicrobial chemical therapy that pig is taken place, 3,609-613/1977/) (Antimicrob.Chemother.3,609-613/1977/), the e. coli septicemia of cholera, respiratory tract disease and poultry that fetal membrane delay, metritis, pneumonia, chicken are taken place is effective.Apramycin is quite effective to the mastitis of treatment Gram-negative pathogen and the microbial cow of Gram-positive cause of disease.MMA(metritis-mastitis-agalactia the disease that can also be used for the treatment of sow) syndrome.Apramycin has strong especially effect to the pseudomonas of mastitis cause of disease.
Because the drug-fast generation of cell, apramycin and other chemotherapeutic being used in combination have appearred, this being used in combination in belgian patent description 886, on No. 765 explanation is arranged, in this part patent specification, proposed to treat the infection of colibacillosis and mycoplasma with the aminoglycoside antibiotic (apramycin, tobramycin, nebramycin) and the combination of macrocyclic lactone (safe Lip river rhzomorph, spiramycin, amimycin).
We made the effect situation that the pathogen that aminoglycoside and tiamulin cultivate ill animal is studied in experiment on one's body.The present invention is based on the recognition exactly, promptly when hydrogen Fumaric acid tiamulin (tiamulin hydrogen fumarate) and aminoglycoside antibiotic (streptomycin, neomycin, kanamycin, tobramycin, Togoplus, apramycin, gentamycin) when being used in combination, except the antimicrobial spectrum scope of each component increase and, its effect is not only to add up, combination drug also has cooperative effect, component is had an effect each other, thereby makes the antibiotic concentration of each component drop to low concentration beyond expectation.
Therefore, the relevant novel anti rhzomorph combination drug of the present invention with cooperative effect, can be used for treating the infectious disease of respiratory tract or urinary system and the septicemia of poultry, this combination drug is made up of antibiotics hydrogen Fumaric acid tiamulin (tiamulin hydrogcn fumarate) and aminoglycoside antibiotic or its salt of allowing in pharmacy, its weight combinations ratio is 5: 1 to 1: 5, and is mixed and made into medicine with last used inert of veterinary and nontoxic carrier.
The cooperative effect of new medicine of the present invention can show by microbiological analysis method.In order to understand the present invention better, use with the homologous culture of pathogen as test organisms.The present invention has determined the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of tiamulin and aminoglycoside.
Following form has been listed the data that microbiological analysis method determines, thereby has confirmed cooperative effect.
Shown in the following tabulation lattice, when with any tiamulin aminoglycoside combination drug, all test organismss all are controlled at low-down concentration.The reinforcing degree of antibacterial ability is 4 to 8 times, as in vitro, can reach 200 to 400 times.This means, just can stop the growth of bacterial strain with quite low pharmaceutical quantities.
The unit of MIC and MBC value is a mcg/ml in the following tabulation.
Because medicine of the present invention has cooperative effect, so can be applied with lower and more economical dosage.Because its antibacterial range enlarges, this quasi drugs can also successfully be used for treating respiratory tract and the gynaecopathia that is caused by mycoplasma and secondary bacterial complication again.
The additional advantage of medicine of the present invention has been to reduce the probability of toxigenicity side effect, has shortened the necessary reagent removal time preventing the occurring drug residue thing in the edible article, these advantages all be since in the medicine dosage of aminoglycoside reduced.
Combination drug of the present invention can that is to say by known process production, active component and veterinary gone up available carrier mix or be dissolved in the carrier.
The dosage form of medicine can be carried out sampling as the case may be, as is used for orally, then is blended in the feedstuff in large quantities or is blended in the drinking-water, perhaps domestic animal single or in groups is done the parenteral treatment.
The mode of parenteral applications can be a muscle, in intrauterine or the capsule.The preparation that the present invention makes parenteral applications is dispersed on the carrier, and for well, the weight mixing ratio of preparation is 1: 1 to 1: 50 to carrier with lactose, then, with 1: 1 to 1: 25 weight ratio this mix preparation is dissolved in the appropriate solvent, solvent is with water, dimethyl formamide, vegetable oil is for well.The oral dose of the combination drug of hydrogen Fumaric acid tiamulin and aminoglycoside antibiotic just can prevent and treat the gastroenteritis that gram negative bacteria causes fully with 10 milligrams/kg body weight.
For bacillus coli, klebsiella and Salmonella infectious disease, oral combination drug of the present invention also can reach good effect.
Combination drug of the present invention carries out intramuscular injection with the dosage of 10 milligrams/kg body weight, can also be used for the treatment of the bronchopneumonia of all animals, pasteurellosis, Listeriosis and staphylococcal infectious disease.
Dosage with every animal 5.0 gram is placed on intrauterine, can also prevent the metritis after the calving or be used for the treatment of fetal membrane to be detained.
Dosage with 0.5 gram active ingredient/1/4th breast carries out intracapsular injection, mastitis that can prevent gram-positive bacterium and gram negative bacteria to cause not only, and can also prevent mycoplasma.
The present invention is further described with reference to following example, but is not limited to these examples, and just dosage range requires with reference to these examples.
Example 1
2.5 gram hydrogen Fumaric acid tiamulins and 2.5 gram streptomycin sulfates are injected in the capsule that intrauterine use.
Put into the intrauterine of cow with a capsule every day.
25 cows are treated after calving immediately, and in 24 hours, just can return to the past rapidly and stop to discharge Excreta in the uterus.
Example 2
0.1 gram hydrogen Fumaric acid tiamulin and 0.5 gram polygynax are dissolved in the distilled water for injection.
Again this solution is injected the position that milk has been extracted fully in the capsule by the nipple tubule once a day.
Continuous three days five cow heads with 10 milliliters of such preparation for treating trouble mastitis, antibiotics injects breast by the nipple tubule, and clinical state and secretory action have just returned to normal condition.The result of Micro biological Tests is negative.
Example 3
0.1 gram hydrogen Fumaric acid tiamulin and 0.2 gram kanamycin sulfate are dissolved in 10 milliliters of waters for injection.
Again this solution is carried out intramuscular injection with the dosage of 1 milliliter of per 10 kg body weight once a day.
Carry out intramuscular injection for three days on end and treat the pig (average weight is the 12-15 kilogram) of 15 milk that broken suffering from dense dermatitis.After carrying out a week of above-mentioned treatment, the skin Jiu Quan More of these pigs, crust has also disappeared.
Example 4
With 200.0 gram hydrogen Fumaric acid tiamulins and 100.0 gram sulphuric acid apramycins and 700.0 gram lactose homogenization, then this preparation of 0.2 gram is dissolved in 1 liter of animal drinking-water.Treatment continues 5 days.
Suffer from 350 pigs of dysentery with in advance medicine being dissolved in this preparation for treating in the animal drinking-water.These pigs are easy to accept these medicinal waters.By second day, " hemorrhagic diarrhea " just stopped, and at the 4th day that treats, it is normal that the clinical state of these pigs has recovered again.
Example 5
With 1600.0 milligrams of hydrogen Fumaric acid tiamulins, 400.0 milligrams of gentamycin sulfate and 3000.0 milligrams of lactose homogenization, the water soluble preparation that 5 grams are obtained like this is dissolved in 100 milliliters of drinking waters again.
45 pigletss that infected by the diarrhoea bacillus coli are divided into 5 groups, these pigletss in the needleless injector with the above-mentioned solution of the oral dose of 0.5 milliliter/kg body weight.Behind the seance, 45 all pigs have all returned to health status.
Example 6
300 milligrams of hydrogen Fumaric acid tiamulins and the homogenize of 100 milligrams of sulphuric acid tobramycins are in 10 milliliters of oils for injection.
Allow 10 milch cows that suffered from the mastitis that transmitted composite cause of disease (Streptococcus, Rhodopseudomonas) causes accept treatment with this preparation, preparation is the breast of having extracted fully by nipple tubule injection milk once a day.After the treatment, breast and milk have all returned to normal condition.In the milk sample of collecting after 1 week for the treatment of, body does not find the cause of disease.
Example 7
20.0 gram hydrogen Fumaric acid tiamulin and 10.0 gram Togopluses are dissolved in 70 milliliters of oils for injection equably.
Allow 24 to suffer from diarrheal calf that the diarrhoea bacillus coli causes and continuous three days accept to treat with the intramuscular injection that the dosage of 1 milliliter/10 kg body weight carries out with this preparation.After the injection, diarrhoea has just stopped for the first time, and milk digestion amount has also increased.
Claims (2)
1, preparation is used for the treatment of the method for the novel anti rhzomorph combination drug with cooperative effect of the respiratory tract of domestic animal and urinary system infectious disease and septicemia, it is characterized in that, with antibiotics hydrogen Fumaric acid tiamulin and aminoglycoside antibiotic or its salt that in pharmacy, allows, mix with 5: 1 to 1: 5 part by weight, go up available carrier with inert and nontoxic veterinary then and mix.
According to the method for claim 1, it is characterized in that 2, its amino glucosides antibiotics is to choose from one group of antibiotics that comprises streptomycin, neomycin, kanamycin, tobramycin, Togoplus, apramycin and gentamycin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 85101456 CN1015418B (en) | 1984-03-28 | 1985-04-01 | Preparation method with new drug regimen of cooperative effect |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU122584A HU191399B (en) | 1984-03-28 | 1984-03-28 | Process for the production of new compound medicine of synergic effect |
| CN 85101456 CN1015418B (en) | 1984-03-28 | 1985-04-01 | Preparation method with new drug regimen of cooperative effect |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN85101456A true CN85101456A (en) | 1987-01-17 |
| CN1015418B CN1015418B (en) | 1992-02-12 |
Family
ID=25741421
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 85101456 Expired CN1015418B (en) | 1984-03-28 | 1985-04-01 | Preparation method with new drug regimen of cooperative effect |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1015418B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101417965B (en) * | 2008-12-01 | 2012-01-04 | 浙江升华拜克生物股份有限公司 | Method for recovering diethylamino ethanethiol from taimulin production waste water |
-
1985
- 1985-04-01 CN CN 85101456 patent/CN1015418B/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101417965B (en) * | 2008-12-01 | 2012-01-04 | 浙江升华拜克生物股份有限公司 | Method for recovering diethylamino ethanethiol from taimulin production waste water |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1015418B (en) | 1992-02-12 |
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