CN103933086A - Creat/amikacin-containing compound medicine for livestock and fowl - Google Patents

Abstract

The invention relates to a compound medicine for livestock and poultry containing andrographis paniculata and amikacin, which consists of the following raw materials in parts by weight: 7-30 parts of amikacin and 10-160 parts of andrographis paniculata. Mix the raw materials and prepare them into powders, tablets, oral liquids or granules, and add them to livestock and poultry feeds according to the amount of 0.1-7g/kg feed, which can reverse the resistance of bacteria to antibacterial drugs, thereby improving The therapeutic effect of antibacterial drugs can greatly reduce drug costs and drug residues, create higher economic benefits for farmers, and ensure human food safety.

Description

A compound drug for livestock and poultry containing andrographis paniculata and amikacin

technical field

The invention belongs to the technical field of treating Escherichia coli infection in livestock and poultry, and in particular relates to a compound medicine for livestock and poultry containing andrographis paniculata and amikacin.

Background technique

Escherichia coli is a common conditional pathogen and a common disease. It can cause acute sepsis, peritonitis, hepatitis, pneumonia, enteritis and other severe infections in chickens, and can also be secondary or mixed with viral diseases. , causing huge economic losses to the farming industry. Amoxicillin, ampicillin, ceftiofur, ceftriaxone, amoxicillin/clavulanic acid, ampicillin/sulbactam and other β-lactam ring antibiotics are commonly used important drugs for the prevention and treatment of this disease. The degree of scale intensification is increasing, and the use of drugs is becoming more and more widespread. There are more and more drug-resistant strains, and there are more reports on the drug resistance of E. coli. Studies have confirmed that one of the main mechanisms of drug resistance is the production of β-lactamase, especially extended-spectrum β-lactamase (Extended-Spectrum β-lactamase, ESBLs), which can strongly and rapidly hydrolyze β-lactamase. The amide ring makes these antibiotics lose their antibacterial activity. ESBLs are the most important enzyme type of β-lactamases. It is not only resistant to third-generation cephalosporins and aztreonam, but also cross-resistant to aminoglycosides, quinolones, and sulfonamides. It is only resistant to carbapenems, cephalosporins, and Sensitivity to mycophenes. Many literatures have reported that the multidrug resistance of Escherichia coli is closely related to the production of ESBLs, which has attracted more attention at home and abroad. The inventor has recently carried out studies on the detection and extraction of food animal-derived pathogenic bacteria ESBLs, the hydrolysis rate of enzymes on antibiotics, and the enzyme-inhibiting protective effects of sulbactam, tazobactam and traditional Chinese medicines. The drug sensitivity of some ESBLs Escherichia coli Tests showed that its multi-drug resistance rate was significantly higher than that of non-ESBLs strains. In addition, the results also showed that ESBLs-producing strains were not only severely resistant to third-generation cephalosporins such as ceftiofur, but also resistant to fluoroquinolones, aminoglycosides, sulfonamides, and fosfomycin. Severe multidrug resistance. The inventor isolated fosfomycin-resistant Escherichia coli producing the fosA3 drug-resistant gene from ESBLs-producing strains, which further enhanced the drug resistance of the bacteria. The drug resistance of Escherichia coli increases the cost of drugs for farmers, prolongs the course of treatment, increases the mortality of livestock and poultry, brings greater economic losses to production, and increases the risk of drug residues in livestock and poultry. Therefore, in actual production, there is an urgent need for a drug that can have a better therapeutic effect on Escherichia coli no matter whether it is drug-resistant or not, and can shorten the course of treatment, reduce mortality, reduce economic losses and reduce drug residues, and create more benefits for farmers. High economic benefits, but also to protect human health and safety.

Contents of the invention

The technical problem to be solved in the present invention is to provide a compound drug for livestock and poultry containing Andrographis paniculata and Amikacin, which can kill bacteria quickly and overcome the poor curative effect and large dosage of antibacterial drugs due to drug resistance. , high residual and high cost defects, avoiding the problem of narrow bactericidal spectrum and slow bactericidal of simple traditional Chinese medicine.

In order to solve the above technical problems, the present invention adopts the following technical scheme: a compound drug for livestock and poultry containing Andrographis paniculata and Amikacin, which consists of the following raw materials in parts by weight: 7-30 parts of Amikacin, 10-160 parts of Andrographis paniculata share.

The compound medicine is prepared into powder, tablet, oral liquid or granule.

The preparation method of the compound medicine is as follows: pulverize andrographis paniculata through a 60-mesh sieve, mix with powdered antibacterial medicine, and prepare powder, tablet, oral liquid or granule according to conventional methods.

Aiming at the problem of drug resistance in Escherichia coli infection in livestock and poultry at present, the inventor used Guangxi characteristic traditional Chinese medicine Andrographis paniculata and antibacterial drugs to form a compound drug. Studies have shown that adding Andrographis paniculata to antibacterial drugs can reverse the resistance of bacteria to antibacterial drugs, thereby improving the therapeutic effect of antibacterial drugs. The compound drug is made into powder, tablet, oral liquid or granule according to conventional methods, and added to livestock and poultry feed according to the addition amount of 0.1-7g main drug/kg feed, which can greatly reduce the cost of drug use and drug residues , to create higher economic benefits for farmers, but also to ensure food safety.

Detailed ways

1. Research on the reversal effect of Andrographis paniculata on antibacterial drug resistance

Antibacterial drugs themselves have the effect of treating Escherichia coli, but due to the strong drug resistance of Escherichia coli producing ESBLs drug resistance genes, antibacterial drugs do not show a good therapeutic effect under normal dosage conditions.

In order to verify the reversal effect of Andrographis paniculata on antibacterial drug resistance, the minimum inhibitory concentration of antibacterial drugs against E. The sub-inhibitory concentration of Escherichia coli strains producing ESBLs and fosA3 drug-resistant genes, and then adding Andrographis paniculata paniculata with sub-inhibitory concentration in the culture medium and then using the micro test tube double dilution method to culture and determine the minimum inhibitory concentration of antibacterial drugs; using the continuous passage method Subculture ESBLs- and fosA3-resistant Escherichia coli strains with the same subinhibitory concentration of Andrographis paniculata and the same concentration of antibacterial drugs until the observed minimum inhibitory concentration of antibacterial drugs becomes smaller than that before subculture More than 4 times, it can be judged that Andrographis paniculata has drug resistance reversal effect on antibacterial drugs. The statistics of the test results are shown in Table 1:

Table 1 Subinhibitory concentration (0.25g/mL) Andrographis paniculata subculture caused changes in MIC of ESBLs and fosA3 Escherichia coli western medicine (μg/mL).

It can be seen from the above table that the minimum inhibitory concentrations of antibacterial drugs against drug-resistant Escherichia coli are all reduced by more than 4 times, which can be judged that Andrographis paniculata has drug resistance reversal effect on ESBLs-producing and fosA3 drug-resistant Escherichia coli.

Two, the application example of compound medicine of the present invention

Prepare embodiment 1-embodiment 8 according to the following method: After Andrographis paniculata is crushed through a 60 mesh sieve, as the basic raw material, put it into a mixer with powdered antibacterial drug in proportion by weight and mix evenly, and mix the compound recipe according to a conventional method The drug is prepared as a formulation product.

The formula of table 2 embodiment 1-8 and preparation dosage form

serial number Antibacterials Andrographis dosage form Example 1 Amikacin 20g 80g Powder Example 2 Amikacin 13g 10g tablet Example 3 Amikastar 7g 160g oral liquid Example 4 Amikastar 30g 110g Granules Example 5 Amikacin 15g 120g Powder Example 6 Amikacin 25g 50g tablet Example 7 Amikacin 10g 80g oral liquid Example 8 Amikastar 30g 160g Granules

The inventor obtained the compound drug product by the above-mentioned embodiment and carried out the following experiments:

1. The curative effect experiment of the compound drug product of embodiment 1-4 gained to the piglet diarrhea of 42 days of age

Clinical symptoms: 42-day-old piglets in a pig farm in Hengxian County, Guangxi. After weaning and turning around, the pigs began to have diarrhea and pull watery feces. The feces contained undigested feed. The pig died of dehydration due to diarrhea, and there was no vomiting symptom. The farmer used a variety of drugs, but the treatment did not have the desired effect.

Necropsy lesions: After necropsy, the intestinal wall of the pig is thin, especially in the rear end of the small intestine and the colon, the intestinal mucosa is shed, and the intestinal wall is congested and bleeding.

Laboratory Diagnosis: Stained slices of the lesioned liver were taken, Gram stained, observed under a microscope, and red Gram-negative bacilli were seen; it was preliminarily determined to be Escherichia coli disease. Through Escherichia coli culture and biochemical test identification, it was judged that the piglets were infected with Escherichia coli disease, and PCR amplification proved that there were CTX-M type ESBLs drug resistance gene and fosA3 drug resistance gene.

Experimental medication scheme: the diseased pigs are divided into 6 groups for administration, the first group is administered according to the addition amount of 1g/kg feed with embodiment 1, and the second group is administered according to the addition amount of 0.5g/kg feed with embodiment 2, The third group uses embodiment 3 to administer according to the addition amount of 7g/kg feed, and the fourth group uses embodiment 4 to administer according to the addition amount of 1.3g/kg feed; The fifth group uses amikacin powder according to the dosage of 0.3g/kg The addition amount of kg feed was administered, and the sixth group was administered with Andrographis paniculata coarse powder according to the addition amount of 7g/kg feed; the above six groups of medication schemes were used continuously for 5 days.

Feedback on the use effect: 2 days after the first group to the fourth group of medication, the pigs no longer pull watery feces, the feces are formed, and the feces no longer contain feed. Continue to use for 3 days, and the pigs are cured; 2 days after the fifth group of medication, The pigs are still unhealthy, continue to use for 3 days, and basically recover to health, but some still have mushy feces, but after 3 days of stopping the drug, the pigs relapse; 2 days after the sixth group of drugs, there is no obvious improvement in the pigs, continue to use for 3 days , the pigs continued to have diarrhea, and the rest were more serious. It can be seen that the curative effect of the compound drug containing Andrographis paniculata is better than that of Amikacin and Andrographis paniculata alone.

2. The curative effect experiment of the compound drug product of embodiment 5-8 gained to the meat duck diarrhea of 35 days old

Clinical symptoms: A duck farm in Guiping, Guangxi, 35-day-old meat ducks, the ducks pulled watery feces, and there were obvious undigested feed in the feces. Individual ducks with severe diarrhea gradually appeared soft feet and died slowly.

Necropsy lesions: the dead ducks were seriously dehydrated, some ducks were still quite large, their livers were swollen and congested, some ducks had white membranes on their livers, and the air sacs were cloudy. The initial diagnosis was E. coli or duck serositis.

Experimental medication scheme: the diseased duck group is divided into six groups for administration, the first group is administered according to the addition amount of 2.5g/kg feed with embodiment 5, and the second group is administered according to the addition amount of 1g/kg feed with embodiment 6, The third group is administered according to the addition amount of 2.5g/kg feed with embodiment 7, and the fourth group is administered according to the addition amount of 1.7g/kg feed with embodiment 8; The fifth group uses amikacin powder according to 0.3g The addition amount of /kg feed was administered, and the sixth group was administered with Andrographis paniculata coarse powder according to the addition amount of 4g/kg feed; the above six groups of medication schemes were all continuously used for 5 days.

Feedback on the use effect: 3 days after the first group to the fourth group of medication, the sick ducks no longer pull watery feces, the feces are formed, and no dead ducks appear. Continue to use for 2 days, and the ducks are basically cured; 3 days after the fifth group of medication, The effect of the duck flock is not obvious, and many of them still pull watery feces, containing undigested feed. They continue to use for 2 days, and they are slightly better, but not completely, and dilute watery feces still appear. The farmers use the compound obtained in Example 5 instead. After using the medicine for 3 days, all the feces became normal; after 3 days of taking the medicine in the sixth group, the ducks did not change significantly, and continued to use it for 2 days, and the death of the ducks was still not effectively controlled. It can be seen that the compound drug containing Andrographis paniculata has better curative effect on duck diarrhea than the single drug.

Claims (2)

1. A compound medicine for livestock and poultry containing Andrographis paniculata and Amikacin, characterized in that it consists of the following raw materials in parts by weight: 7-30 parts of Amikacin, 10-160 parts of Andrographis paniculata. 2. The compound medicine for livestock and poultry containing Andrographis paniculata and Amikacin according to claim 1, characterized in that, said compound medicine is prepared into powder, tablet, oral liquid or granule.