KR101047591B1 - Combination antibiotic composition for animals - Google Patents

Abstract

The present invention relates to a composite antibiotic composition for animals, and more specifically, cerapalexin (cephalexine) and enrofloxacin (enrofloxacin) 1: 0.25 ~ 0.25: 1 by weight ratio of the combination of the animal's mastitis compared to a single prescription The present invention relates to a composite antibiotic composition for animals having an excellent effect on prevention and treatment.

Cephalexine, enrofloxacin, mastitis

Description

Antibiotic complex formulation for animal use

The present invention is a combination compound of ceparexine (cephalexine) and enrofloxacin (enrofloxacin) 1: 0.25 ~ 0.25: 1 by weight of the composite antibiotic composition for animals having an excellent effect on the prevention and treatment of mastitis in animals compared to the single prescription It is about.

Separexin is a first-generation cephalosporin-based antibiotic whose line name is D-7- (2-amino-2-phenylacetamido) -3-methyl-8-oxo-5-thia-1-azabicyclo [ 4. 2. 0] -oct-2-ene-2-carboxylic acid. Separexin, like other beta-lactam antibiotics (penicillin and cephalosporin), is a bactericidal antibiotic that exhibits antimicrobial activity by inhibiting bacterial cell wall synthesis. Beta-lactam antibiotics inhibit the third stage of bacterial cell membrane formation by binding to one or more Penicillin Binding Proteins (PBPs) present in sensitive bacterial cell walls. Thus, the antimicrobial activity of beta lactam antibiotics depends on the binding affinity with these PBPs. For example, the affinity of staphylococci with PBPs is greater in first-generation cephalosporins than in third-generation cephalosporins. However, the affinity for enterobacteriaceae bacteria and PBPs is generally greater for third generation cephalosporins. In addition, the antimicrobial activity of individual antibiotics depends on the stability of beta lactam produced by Gram-positive bacteria and negative bacteria and the Gram-negative bacterial outer membrane permeability. Cephalexin, like other first-generation cephalosporins, exhibits very high antimicrobial activity against most Gram-positive bacteria, and high antimicrobial activity to some Gram-negative bacteria.

Examples of fluoroquinolone-based antibiotics include nofloxacin, ciprofloxacin, enrofloxacin, ofloxacin, and pefloxacin. Of these, four types of nofloxacin, Ciprofloxacin, Ofloxacin, and pefloxacin are prohibitively manufactured and imported from Korea. It was banned for animal use in accordance with the Food and Drug Administration, '07 .8.2, '07 .8.10 [Food Safety Policy Council]).

Enrofloxacin is a fluoroquinolone carboxylic acid antibiotic and the system name is 1-cyclopropyl-7- (4-ethyl-1-pyrerazinyl) -6-fluoro-1,4-dihydro- It is a bactericidal antimicrobial agent that specifically inhibits the formation of DNA supercoils by inhibiting DNA gyrase (topoisomerase II), which is used only for animals as 4-oxo-3-quinolone-carboxylic acid and is essential for DNA replication and transcription. Escherichia coli (E. coli), Pseudomonas Oh Rouge on labor (Pseudomonas aeruginosa), keulrep City in Ella (Klebsiella spp.), Enterococcus batteo (Enterobacter), Campanile days bakteo (Campylobacter), when Gela (Shigella), salmonella (Salmonella) ah as Pseudomonas (Aeromonas), by a brush Russ (Haemophilus), Proteus (Proteus), Yersinia (Yersinia), Serratia marcescens (Serratia), to exert a strong antibacterial activity to pathogenic bacteria such as Vibrio species (Vibrio species) in It can be said to have excellent therapeutic and prophylactic effects. Enlofloxacin is a unique mechanism of action as described above does not cause cross-resistance with other antimicrobial agents, and because it does not have a beta lactam ring in its chemical structure, it is stable to beta lactamase and is very effective for beta lactamase producing strains.

As described above, separexcin and enlofloscin are antibiotics that are widely used in veterinary clinical fields, but veterinary pharmacological studies on these complex formulations have not been made at home and abroad.

Therefore, the present inventors have established an optimal combination antibiotic composition, and as a result of the research efforts, developed an animal complex antibiotic composition of separexin and enlofloxacin excellent in inhibiting the pathogenic microorganisms of animals, and when used alone and existing The present invention was completed by confirming that an excellent synergistic effect was observed in the prevention and treatment of mastitis in animals compared to the combination preparations used in the present invention.

Therefore, the present invention provides an antimicrobial antibiotic composition for animals containing ceparexin and enlofloxacin, which is excellent in the inhibitory effect of pathogenic microorganisms causing mastitis in animals, in a weight ratio of 1: 0.25 to 0.25: 1. have.

The present invention is characterized by a composite antibiotic composition for animals containing ceparexcin and enlofloxacin mixed in a weight ratio of 1: 0.25 ~ 0.25: 1.

Hereinafter, the present invention will be described in detail.

The present invention relates to a composite antibiotic composition for animals having an excellent effect on the prevention and treatment of mastitis in animals compared to a single prescription and conventional combination formulations by combining ceparexcin and enlofloxacin in a weight ratio of 1: 0.25-0.2: 1. will be.

The present invention relates to a pharmaceutical composition for animals of a novel composition, which is economical and has excellent antibacterial activity against mastitis causative organisms by optimizing the mixing ratio of ceparexin and enlofloxacin, and in the present invention, between ceparexin and enlofloxacin To examine the interactions between the mixtures and to determine the correlation between the mixing ratios, ceparexin and antimicrobial antibiotics were tested for multi-resistant microorganism, that is, Gram-positive and negative bacteria isolated from chickens, pigs, and cattle infected with various bacterial diseases. The antimicrobial effect of the enrofloxacin combination formulation was measured by testing with minimum inhibition concentration (MIC).

In the present invention, the mixing ratio of separexcin and enlofloxacin is preferably in a weight ratio of 1: 0.25 to 0.25: 1, and more preferably in a weight ratio of 1: 0.5 to 0.5: 1. If the mixing ratio is less than 1: 0.25 not only is uneconomical due to the high price of separexin, but also lowers the antimicrobial effect against resistant pathogens of the mixed agent. There is a problem that is difficult to achieve.

Furthermore, in the present invention, the mixing of enlofloxacin with ceparexin is more effective than the combination of nofloxacin, ciprofloxacin and ofloxacin, which are the same fluoroquinolone antibiotics as enrofloxacin. It was confirmed that the effect was superior.

The complex antibiotic composition of the present invention comprises ceparexin and enlofloxacin mixed in a weight ratio of 1: 0.25 to 0.25: 1 as an active ingredient, and can be easily carried out by those of ordinary skill in the art. It may be formulated as an additive, powder, veterinary injection, oral solution and ointment according to the possible method.

On the other hand, animal additives and powders containing the complex antibiotic of the present invention is prepared by containing a commonly used sugars, such as vitamins, glucose, lactose, starch, powder, vermiculite or various powders and enzymes in the range of usage.

In addition, when formulating the complex antibiotic of the present invention as an ointment, it may further include an antioxidant, a pigment, a moisturizing agent, a solvent and the like. At least one selected from vitamins A, C, E and derivatives thereof as the antioxidant, and as the pigment, blue 1, blue 2, red 2, red 3, yellow 2, yellow 4 and yellow 5 At least one selected may be used at least one selected from glycerin, petrolatum, and wax as the moisturizing agent, and at least one selected from olive oil, soybean oil, and coconut oil as the solvent.

Administration of the complex antibiotics prepared in the present invention, the additives are administered in a mixed feed, formulated as a powder, animal injections, oral solutions and ointments.

In the case of the compound antibiotics mixed in the ratio set by the present invention, the additive is administered at 200 g to 10 kg (typically 500 g to 2 kg) per ton of feed, in particular, when administered as an ointment, 0.5 to 2 (usually one) per one cow's milk. It is preferable to use (one ointment contains 200 to 1000 mg of antibiotic).

The present invention can suppress the emergence of antibiotic resistance strains by mixing and mixing ceparexin and enloflosine in the above ratio as described above, by reducing the dose in combination administration can reduce the toxicity than when administered alone It can be used effectively in the prevention and treatment of mastitis by acting more effectively when a complex infectious disease occurs.

As described above, the present invention can suppress the emergence of antibiotic resistance strains by mixing and mixing ceparexin and enloflosine in the above ratio, and by reducing the dose in combination administration to reduce the toxicity than when administered alone It can be used effectively in the prevention and treatment of mastitis by acting more effectively when a complex infectious disease occurs.

Hereinafter, the present invention will be described in detail with reference to the following examples, but the scope of the present invention is not limited to these examples.

Example 1 Comparison of Antimicrobial Effects by Strains

1) MIC Measurement

The minimum growth inhibitory concentration (MIC) of mastitis causative bacteria collected from the field was measured using Separexin and Enloflosacin.

2) materials and devices

① Antibiotics:

   Separexin (93.6%): 341.88 mg / 50 ml (= 640 μg / 100 μl)

   Enlofloscin (100%): 320 mg / 50 ml (= 640 µg / 100 µl)

② Test tube, 250 ml flask, 30 ml syringe, filter for 0.2 μm syringe, spectrophotometer

③ Badge

a. Proliferation Medium: Tryptic Soy Agar (TSA), Tryptic Soy Broth (TSB)

               & Brain Heart Infunsion Agar

b. Susceptibility Testing Medium: TSB & BHI

④ Experimental strain

a. 7 strains from the field

   Staphylococcus epidermidis

   2 species of Staphylococcus aureus

   Streptococcus uberis

   Enterococcus

   Bacillus cereus

   Genus Klebsiella.

b. Two strains distributed by Korea Research Institute of Bioscience and Biotechnology:

   Pseudomonas aeruginosa (ATCC 27853)

   Staphylococcus aureus (ATCC 25923)

3) The experimental strain was inoculated into 100 ml of liquid medium (/ 250 ml flask) and shaken at 37 ° C. for 24 hours. Culture medium was Mcfarland scale No. Diluted in saline to turbidity corresponding to 0.5. The liquid medium was sterilized by putting 10 ml in the first test tube and 5 ml each in the remaining test tube. 100 μl of the antimicrobial agent was added to the sterilized first test tube, and diluted twice stepwise. 100 μl of the bacterial culture solution was added to the test tube containing the antimicrobial agent, and shaken at 37 ° C. for 18 to 20 hours, and then the absorbance (600 nm) was measured using a spectrophotometer.

4) MIC & FIC (FRACTIONAL INHIBITION CONCENTRATION) results

FIC (Ce) + FIC (En) = 1: Simple additive effects

FIC (Ce) + FIC (En) <1: Synergism

FIC (Ce) + FIC (En)> 1: Antagonism, if either FIC (Ce) or FIC (En)> 1

FIC (Ce) + FIC (En)> 1: No interaction, if neither FIC (Ce) or FIC (En)> 1

TABLE 1

Staphylococcus aureus (ATCC 25923)

Antibiotic
Ce: En Ce (µg / ml) En (μg / ml) Ce / En (µg / ml) FIC Index Interpretation 1: 1 2 One 0.5 / 0.5 0.75 Synergism 1: 0.75 2 One 0.5 / 0.375 0.625 Synergism 1: 0.5 2 One 0.125 / 0.0625 0.125 Synergism 1: 0.25 2 One 0.5 / 0.125 0.375 Synergism 0.75: 1 2 One 0.1875 / 0.25 0.344 Synergism 0.5: 1 2 One 0.25 / 0.5 0.625 Synergism 0.25: 1 2 One 0.125 / 0.5 0.563 Synergism

As shown in Table 1, the combination preparation of the present invention is 1.33 to 8 times (1 / 0.75 to 1 / 0.125) superior to the antibacterial activity against Staphylococcus aureus (ATCC 25923) bacteria compared to the administration alone group In particular, the mixing ratio of 1: 0.25 ~ 0.25: 1 showed an excellent effect.

TABLE 2

Staphylococcus epineremis

Antibiotic
Ce: En Ce (µg / ml) En (μg / ml) Ce / En (µg / ml) FIC Index Interpretation 1: 1 2 0.25 0.125 / 0.125 0.563 Synergism 1: 0.75 2 0.25 0.25 / 0.1875 0.875 Synergism 1: 0.5 2 0.25 0.25 / 0.125 0.625 Synergism 1: 0.25 2 0.25 0.5 / 0.125 0.75 Synergism 0.75: 1 2 0.25 0.09375 / 0.125 0.547 Synergism 0.5: 1 2 0.25 0.25 / 0.5 2.125 No interaction 0.25: 1 2 0.25 0.0625 / 0.25 1.031 No interaction

As shown in Table 2, the combination preparation of the present invention is 1.14 ~ 1.82 times (1 / 0.875 ~ 1 / 0.547) more excellent antimicrobial activity against Staphylococcus epineridis bacteria compared to the single administration group, in particular 1 The mixing ratio of: 0.25 to 0.75: 1 showed an excellent effect.

[Table 3]

Staphylococcus aureus

Antibiotic
Ce: En Ce (µg / ml) En (μg / ml) Ce / En (µg / ml) FIC Index Interpretation 1: 1 4 0.5 0.25 / 0.25 0.563 Synergism 1: 0.75 4 0.5 0.25 / 0.1875 0.438 Synergism 1: 0.5 4 0.5 0.5 / 0.25 0.625 Synergism 1: 0.25 4 0.5 1 / 0.25 0.75 Synergism 0.75: 1 4 0.5 0.09375 / 0.125 0.273 Synergism 0.5: 1 4 0.5 0.125 / 0.25 0.531 Synergism 0.25: 1 4 0.5 0.125 / 0.5 1.031 No interaction

As shown in Table 3, the combination preparation of the present invention has 1.33 to 3.66 times (1 / 0.75 to 1 / 0.273) more excellent antibacterial activity against Staphylococcus aureus compared to the single-administered group. The mixing ratio of 0.25 to 0.5: 1 showed excellent effects.

[Table 4]

Staphylococcus aureus

Antibiotic
Ce: En Ce (µg / ml) En (μg / ml) Ce / En (µg / ml) FIC Index Interpretation 1: 1 4 4 1/1 0.5 Synergism 1: 0.75 4 4 1 / 0.75 0.438 Synergism 1: 0.5 4 4 2/1 0.75 Synergism 1: 0.25 4 4 2 / 0.5 0.625 Synergism 0.75: 1 4 4 0.75 / 1 0.438 Synergism 0.5: 1 4 4 1/2 0.75 Synergism 0.25: 1 4 4 0.25 / 1 0.313 Synergism

As shown in Table 4, the combination preparation of the present invention is 1.33 to 3.19 times (1 / 0.75 to 1 / 0.313) superior to the antibacterial activity against Staphylococcus aureus compared to the single administration group, in particular 1: In the mixing ratio of 0.25 ~ 0.25: 1 showed excellent effect.

TABLE 5

Streptococcus uberis

Antibiotic
Ce: En Ce (µg / ml) En (μg / ml) Ce / En (µg / ml) FIC Index Interpretation 1: 1 One 2 0.5 / 0.5 0.75 Synergism 1: 0.75 One 2 0.5 / 0.375 0.688 Synergism 1: 0.5 One 2 0.5 / 0.25 0.625 Synergism 1: 0.25 One 2 1 / 0.25 1.125 No interaction 0.75: 1 One 2 0.375 / 0.5 0.625 Synergism 0.5: 1 One 2 0.5 / 1 One Additive 0.25: 1 One 2 0.25 / 1 0.75 Synergism

As shown in Table 5, the combination preparation of the present invention is 1.33 ~ 1.6 times (1 / 0.75 ~ 1 / 0.625) more excellent antimicrobial activity against Streptococcus uberis than the group alone, especially 1: 0.5 ~ The mixing ratio of 0.25: 1 showed excellent effects.

TABLE 6

Enterococcus

Antibiotic
Ce: En Ce (µg / ml) En (μg / ml) Ce / En (µg / ml) FIC Index Interpretation 1: 1 2 32 1/1 0.531 Synergism 1: 0.75 2 32 1 / 0.75 0.523 Synergism 1: 0.5 2 32 1 / 0.5 0.516 Synergism 1: 0.25 2 32 2 / 0.5 1.016 No interaction 0.75: 1 2 32 0.75 / 1 0.406 Synergism 0.5: 1 2 32 1/2 0.563 Synergism 0.25: 1 2 32 0.5 / 2 0.313 Synergism

As shown in Table 6, the combination preparation of the present invention is 1.77 ~ 3.19 times (1 / 0.563 ~ 1 / 0.313) more excellent antibacterial activity against Enterococcus bacteria than the single administration group, in particular 1: 0.5 to 0.25 The mixing ratio of 1 showed excellent effect.

TABLE 7

Bacillus cereus

Antibiotic
Ce: En Ce (µg / ml) En (μg / ml) Ce / En (µg / ml) FIC Index Interpretation 1: 1 64 16 2/2 0.156 Synergism 1: 0.75 64 16 2 / 1.5 0.125 Synergism 1: 0.5 64 16 4/2 0.188 Synergism 1: 0.25 64 16 8/2 0.25 Synergism 0.75: 1 64 16 1.5 / 2 0.148 Synergism 0.5: 1 64 16 1/2 0.141 Synergism 0.25: 1 64 16 1/4 0.266 Synergism

As shown in Table 7, the combination preparation of the present invention has an excellent antimicrobial activity against Bacillus cereus bacteria 3.75 ~ 8 times (1 / 0.266 ~ 1 / 0.125) compared to the single administration group, in particular 1: 0.25 ~ 0.25 The mixing ratio of 1 shows an excellent effect.

[Table 8]

Genus Klebsiela

Antibiotic
Ce: En Ce (µg / ml) En (μg / ml) Ce / En (µg / ml) FIC Index Interpretation 1: 1 > 64 0.25 0.25 / 0.25 1.004 No interaction 1: 0.75 > 64 0.25 0.25 / 0.1875 0.754 Synergism 1: 0.5 > 64 0.25 0.5 / 0.25 1.008 No interaction 1: 0.25 > 64 0.25 0.5 / 0.125 0.013 Synergism 0.75: 1 > 64 0.25 0.0938 / 0.125 0.501 Synergism 0.5: 1 > 64 0.25 0.125 / 0.25 1.002 No interaction 0.25: 1 > 64 0.25 0.0313 / 0.125 0.500 Synergism * The MIC of Ce was interpreted under the assumption that 64 (µg / ml).

As shown in Table 8, the combination preparation of the present invention is 1.32 ~ 76.92 times (1 / 0.754 ~ 1 / 0.013) more excellent antimicrobial activity against the genus Klebsiella compared to the single administration group, in particular 1: 0.75 ~ The mixing ratio of 0.25: 1 showed an excellent effect.

TABLE 9

Pseudomonas aeruginosa (ATCC 27853)

Antibiotic
Ce: En Ce (µg / ml) En (μg / ml) Ce / En (µg / ml) FIC Index Interpretation 1: 1 > 64 4 2/2 0.531 Synergism 1: 0.75 > 64 4 4/3 0.813 Synergism 1: 0.5 > 64 4 4/2 0.563 Synergism 1: 0.25 > 64 4 8/2 0.625 Synergism 0.75: 1 > 64 4 1.5 / 2 0.523 Synergism 0.5: 1 > 64 4 1/2 0.516 Synergism 0.25: 1 > 64 4 0.5 / 2 0.508 Synergism * The MIC of Ce was interpreted under the assumption that 64 (µg / ml).

As shown in Table 9, the combination preparation of the present invention is 1.23 ~ 1.96 times (1 / 0.813 ~ 1 / 0.508) excellent antimicrobial activity against Pseudomonas aeruginosa (ATCC 27853) bacteria compared to the single administration group, in particular The mixing ratio of 1: 0.25-0.2: 1 showed excellent effects.

Example 2: MIC Comparison with Existing Co-Formulations

In order to find the compounding level that maintains the best antimicrobial activity, 1 (w / v)%, that is, 10 μg / ml solution was prepared by varying the mixing ratio (weight basis) of Separexin / Enrofloxacin, Five species (Staphylococcus aureus, Streptococcus uberis, Enterococcus, Bacillus cereus and Klebsiella spp.) Collected from the field were measured and compared with the MIC of Separexin / Nofloxacin. Shown in

TABLE 10

division Ce / En (μg / ml) Ce / Nor (μg / ml) Staphylococcus aureus 1 / 0.75 4/3 Streptococcus uberis 0.5 / 0.375 1 / 0.75 Enterococcus 1 / 0.75 1 / 0.75 Bacillus cereus 2 / 1.5 4/3 Genus Klebsiela 0.25 / 0.1875 0.5 / 0.375 Nor: Norfloxacin
* The composition ratio of the combination formulation is (Ce + En), (Ce + Nor) = 1: 0.75 under the same conditions.

As shown in Table 10, the composite formulation of the present invention can show an effective antimicrobial effect even in a small amount MIC value is significantly smaller than the conventional composite formulation (Ce / Nor).

Formulation Example 1 Preparation of Organic Ointment

Ointments were prepared from the compositions described in Table 11 below.

1. After weighing the moisturizer and the solvent, dry heat sterilization was performed at 160 ° C. for 1 hour, mixed, and then added to the preparation tank and cooled to 50 ° C.

2. Separately, separexin monohydrate, enlofloxacin, and colorant were put in a vinyl container and mixed sufficiently.

3. The raw material separexin monohydrate, enlofloxacin, pigment, and antioxidant mixed in a small amount of sterile solvent were added and stirred to disperse homogeneously.

4. The solution of 3 was added to the solution of 1 and mixed for 30 minutes or more, and the operation was finished.

TABLE 11

division Weight / 8 g Antibiotic Separexin Monohydrate 160.0 mg (titer) Enrofloxacin 200.0 mg Antioxidant Vitamin E Acetate Oil 20.0 mg Pigment Blue 1 20.0 mg Moisturizer vaseline 1.40 g solvent Soybean oil Quantity

Formulation example  2: Preparation of Organic Ointment

The ointment was carried out in the same manner as in Formulation Example 1 to the composition shown in Table 12 below.

TABLE 12

division Weight / 8 g Antibiotic Separexin Monohydrate 160.0 mg (titer) Enrofloxacin 200.0 mg Antioxidant Vitamin E Succinate Oil 20.0 mg Pigment Blue 1 20.0 mg Moisturizer glycerin 1.40 g solvent olive oil Quantity

Formulation Example 3: Preparation of inorganic ointment

The ointment was carried out in the same manner as in Formulation Example 1 to the composition shown in Table 13.

TABLE 13

division Weight / 8 g Antibiotic Separexin Monohydrate 160.0 mg (titer) Enrofloxacin 200.0 mg Antioxidant Vitamin A oil 20.0 mg Pigment Red No. 2 20.0 mg Moisturizer vaseline 1.40 g solvent olive oil Quantity

Formulation Example 4: Preparation of inorganic ointment

The ointment was carried out in the same manner as in Formulation Example 1 to the composition shown in Table 14.

[Table 14]

division Weight / 8 g Antibiotic Separexin Monohydrate 160.0 mg (titer) Enrofloxacin 200.0 mg Antioxidant Vitamin E Acetate Oil 20.0 mg Pigment Red No. 1 20.0 mg Moisturizer glycerin 1.40 g solvent olive oil Quantity

Formulation Example 5: Preparation of Dry Organic Ointment

Ointments were prepared from the compositions described in Table 15 below.

1. After weighing the moisturizer and the solvent, dry heat sterilization was performed at 160 ° C. for 1 hour, mixed, and then added to the preparation tank and cooled to 50 ° C.

2. Separately, separexin monohydrate, enlofloxacin, and colorant were put in a vinyl container and mixed sufficiently.

3. The raw material separexin monohydrate, enlofloxacin, pigment, and antioxidant mixed in a small amount of sterile solvent were added and stirred to disperse homogeneously.

4. The solution of 3 was added to the solution of 1 and mixed for 30 minutes or more, and the operation was finished.

TABLE 15

division Weight / 8 g Antibiotic Separexin Monohydrate 200.0 mg (titer) Enrofloxacin 250.0 mg Antioxidant Vitamin E Acetate Oil 20.0 mg Pigment Blue 1 20.0 mg Moisturizer vaseline 1.40 g solvent Soybean oil Quantity

Formulation Example 6 Preparation of Dry Organic Ointment

The ointment was carried out in the same manner as in Formulation Example 1 to the composition shown in Table 16 below.

TABLE 16

division Weight / 8 g Antibiotic Separexin Monohydrate 200.0 mg (titer) Enrofloxacin 250.0 mg Antioxidant Vitamin E Succinate Oil 20.0 mg Pigment Blue 1 20.0 mg Moisturizer glycerin 1.40 g solvent olive oil Quantity

Formulation example  7: Dry season  Preparation of Ointment

The ointment was carried out in the same manner as in Formulation Example 1 below with the composition shown in Table 17.

TABLE 17

division Weight / 8 g Antibiotic Separexin Monohydrate 200.0 mg (titer) Enrofloxacin 250.0 mg Antioxidant Vitamin A oil 20.0 mg Pigment Red No. 2 20.0 mg Moisturizer glycerin 1.40 g solvent Soybean oil Quantity

Experimental Example: Toxicity Test

Toxicity test of oral administration to the following combination antibiotic composition for animals was carried out as follows.

Combination Antibiotic Composition / 1 g in

Separexin monohydrate 12 mg

Enlofloxacin 15 mg

The experimental animals were prepared from SD (Spraque Dawley) series 4-5 week old rats, and purified and quarantined for 3 days using 44 animals (20 females and 24 males). The age of 44 animals (20 females, 24 males), free feeding of food and drinking water in the cage during the acclimatization and quarantine periods, and only healthy animals were provided for the test.

The experimental group was divided into 0.1 g (recommended amount), 0.3 g, 0.5 g group per kg body weight, and the dose was determined by measuring the weight before administration of the evaluation drug.

Each experimental group was administered orally with a syringe for intragastric administration for rats for 5 consecutive days once a day for each treatment. The dose for each subject was based on body weight at each administration, and administration time was administered at 9-10 am each time, and the control group was fed only drinking water and feed. In order to investigate the histopathologic results after oral administration of experimental animals, body weight was measured by ether anesthesia according to autopsy schedule (before administration, 1, 5, 10, 14 days after administration), blood was collected and an autopsy was performed immediately. The presence of tissue lesions in major organs showed no significant lesions.

Claims (4)

Separexin and enrofloxacin is mixed antibiotic composition for animals, characterized in that it is contained in a weight ratio of 1: 0.5 to 0.5: 1. delete The combination antibiotic composition of claim 1, wherein the complex antibiotic is formulated as a powder, a water soluble agent, an ointment. The complex antibiotic composition for animals according to claim 1, wherein the complex antibiotic is excellent for the prevention and treatment of mastitis.