CN113768872B - Talarmycin injection and application thereof - Google Patents

Talarmycin injection and application thereof Download PDF

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CN113768872B
CN113768872B CN202111228810.9A CN202111228810A CN113768872B CN 113768872 B CN113768872 B CN 113768872B CN 202111228810 A CN202111228810 A CN 202111228810A CN 113768872 B CN113768872 B CN 113768872B
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injection
tulathromycin
stirring
vitamin
solvent
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CN113768872A (en
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田瑞叶
刘漫
赵新祥
王玲
李建国
汪娜
杨申永
韩丙星
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Amicogen China Biopharm Co Ltd
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Abstract

The invention discloses a tulathromycin injection and application thereof, belonging to the technical field of veterinary injection. The invention provides a telapramycin compound injection which is characterized by comprising telapramycin, vitamin C, a solubilizer, a cosolvent and a solvent. The compound injection prepared by the invention is a water-soluble injection, and adopts substituted beta-cyclodextrin as a solubilizer, so that the water solubility and stability of the tulathromycin are improved. Meanwhile, the injection does not need to add a pH regulator and an antioxidant, so that the injection has the advantages of no irritation, high safety, quick response, good solubility and the like.

Description

Talarmycin injection and application thereof
Technical Field
The invention belongs to the technical field of veterinary injection, and particularly relates to a tulathromycin injection preparation and application thereof.
Background
Tulathromycin (Tulathromycin) is an animal-specific semisynthetic macrolide antibiotic developed in the united states that inhibits the biosynthesis of essential proteins by selectively binding to bacterial ribosomal RNAs. They function by promoting dissociation of the polypeptide-tRNA from the ribosome during translocation. Unlike many other macrolide antibiotics, its pharmaceutical effect remains long, in part because of the 3 amino groups in its structure. Talaromyces is a broad-spectrum antibacterial agent and is very sensitive to various pathogenic bacteria of respiratory diseases of pigs and cattle, such as haemolytic Pasteurella, hemorrhagic septicemia Pasteurella, actinobacillus pleuropneumoniae, mycoplasma, haemophilus parasuis, bordetella bronchiseptica and the like, and infectious keratoconjunctivitis of cattle caused by Moraxella bovis.
At present, the macrolide drugs which are widely used in animal production in China and have good effects are tilmicosin and tylosin, but with the prolongation of the use time and the irregular administration, different degrees of drug resistance occur in a plurality of areas, the drug effect of the tylosin is stronger than that of the macrolide drugs widely used in markets such as tilmicosin, tylosin and the like, the macrolide drugs generally have an inhibitory effect on bacteria, and the tylosin has antibacterial and bactericidal effects. The tulathromycin has the advantages of excellent pharmacokinetic properties, quick absorption, short peak time, high bioavailability, high tissue concentration in the lung, long elimination half-life and durable drug effect, has a slow release effect, can provide whole course treatment by single intramuscular injection or subcutaneous administration, and has wide application prospect in veterinary clinic. The medicine is marketed in the European Union and the United states in 2004, and the department of agriculture in 2008 publication No. 957 is allowed to be used in animal production for the first time.
Because the tulathromycin is insoluble in water and soluble in acidic solution, most of tulathromycin injection which is currently marketed is a solution type injection preparation prepared under the conditions of organic solvent/water cosolvent and acidity, the injection is slightly acidic and has large irritation, and injection pain, swelling at injection positions and the like are often caused during injection; the oily injection prepared from the tulathromycin has the defects of slow onset of action and adverse treatment of animals suffering from acute severe infection compared with solution injection; meanwhile, the antioxidant is added into the tulathromycin injection prescription, so that the stability of the medicine is improved, but the medication safety is reduced.
Therefore, the water-soluble tulathromycin compound injection which has no irritation, good safety, quick response and good solubility is provided, and the problem to be solved in the field is urgent.
Disclosure of Invention
The invention discloses a tulathromycin injection and application thereof.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
a tulathromycin compound injection mainly comprises the following components: telamycin, vitamin C, solubilizer and cosolvent, the rest is solvent;
preferably, the component contents are as follows:
Figure GDA0004083129340000021
the rest is solvent;
preferably, the solubilizing agent is a substituted β -cyclodextrin; preferably, the substituted beta-cyclodextrin is any one of hydroxypropyl-beta-cyclodextrin or hydroxyethyl-beta-cyclodextrin or sulfobutyl ether-beta-cyclodextrin or glucosyl-beta-cyclodextrin; more preferably, the substituted β -cyclodextrin is a glucosyl- β -cyclodextrin;
preferably, the weight ratio of the substituted beta-cyclodextrin to the tulathromycin is 1:1;
preferably, the content of the cosolvent component is 3-5g/L;
preferably, the cosolvent is one or two of meglumine, tromethamine or nicotinamide;
preferably, the cosolvent is tromethamine and meglumine,
preferably, the weight ratio of tromethamine to meglumine is: 2:1;
preferably, the solvent is water for injection;
preferably, the preparation method of the tulathromycin composite injection comprises the following steps:
step one: taking a solvent accounting for 90% of the total amount, introducing nitrogen into the solvent, adding a solubilizer and a cosolvent, and stirring for dissolution; adding vitamin C, stirring and dissolving completely, wherein the pH value of the solution is 1.3-1.8;
step two: slowly adding tulathromycin into the solution obtained in the step one, heating until the tulathromycin is dissolved, and stirring and clathrating for a certain time; adding the rest solvent, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection. The pH value of the injection is 5.0-5.5.
Preferably, the solvent is water for injection;
preferably, the pore size of the sterile filtration is 0.22 μm;
preferably, in the second step, the inclusion time is 30 min-120 min, preferably, the inclusion time is 30 min-40 min.
Preferably, in the second step, the temperature during heating is 50-60 ℃;
preferably, the heating time is 30min;
preferably, the temperature at the time of heating is 60 ℃;
preferably, in the third step, the pH value ranges from 5.0 to 5.5, and preferably, the pH value is 5.2.
In summary, the invention discloses a tulathromycin injection and application thereof. The invention provides a telapramycin compound injection, which consists of telapramycin, vitamin C, a solubilizer, a cosolvent and a solvent. The compound injection prepared by the invention is a water-soluble injection, and adopts substituted beta-cyclodextrin as a solubilizer, so that the water solubility and stability of the tulathromycin are improved. Meanwhile, the injection does not need to add a pH regulator and an antioxidant, so that the injection has the advantages of no irritation, high safety, quick response, good solubility and the like.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Figure GDA0004083129340000041
The balance being solvent.
EXAMPLE 1 Talarmycin Compound injection
Figure GDA0004083129340000042
Figure GDA0004083129340000051
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; then cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Comparative example 1
Figure GDA0004083129340000052
The preparation method comprises the following steps: as in example 1.
Comparative example 2
Figure GDA0004083129340000061
The preparation method comprises the following steps: as in example 1.
Comparative example 3
Figure GDA0004083129340000062
The preparation method comprises the following steps: as in example 1.
The samples prepared in example 1 and comparative examples 1 to 3 were compared for stability investigation under conditions of (1) 60℃high temperature for 10 days (2) intense light irradiation 5000Lx 10 days, and the detection indexes are properties, content and pH value. The results were as follows:
results for 0 days:
Figure GDA0004083129340000063
Figure GDA0004083129340000071
results at high temperature for 10 days:
Figure GDA0004083129340000072
results were obtained by illuminating for 10 days:
Figure GDA0004083129340000073
as can be seen from the analysis of the stability test results in tables 1 to 3, the stability of the samples prepared in example 1 is higher than that of the samples prepared in comparative examples 1 to 3, thus demonstrating that the inclusion of tulathromycin by the glucosyl-beta-cyclodextrin employed in example 1 of the present invention improves the stability of tulathromycin.
Example 2: compound telamycin injection
Figure GDA0004083129340000081
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 50 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 1h; then cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 3: compound telamycin injection
Figure GDA0004083129340000082
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 1h; then cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 4: compound telamycin injection
Figure GDA0004083129340000091
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; then cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 5: compound telamycin injection
Figure GDA0004083129340000101
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; then cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 6: compound telamycin injection
Figure GDA0004083129340000102
Figure GDA0004083129340000111
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and nicotinamide with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 7: compound telamycin injection
Figure GDA0004083129340000112
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin and tromethamine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 8: compound telamycin injection
Figure GDA0004083129340000121
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin and the meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 9: compound telamycin injection
Figure GDA0004083129340000122
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin and nicotinamide with the prescription amount, stirring for dissolving, adding the vitamin C with the prescription amount, and stirring for dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 10: compound telamycin injection
Figure GDA0004083129340000131
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 11: compound telamycin injection
Figure GDA0004083129340000141
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 12: compound telamycin injection
Figure GDA0004083129340000142
Figure GDA0004083129340000151
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; cooling to room temperature, adding the rest water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
Example 13: compound telamycin injection
Figure GDA0004083129340000152
The preparation method comprises the following steps:
step one: taking injection water accounting for 90% of the total amount, introducing nitrogen into the injection water, adding the glucose-beta-cyclodextrin, tromethamine and meglumine with the prescription amount, stirring and dissolving, adding the vitamin C with the prescription amount, and stirring and dissolving completely;
step two: slowly adding the prescription amount of tulathromycin, heating to 60 ℃ until the tulathromycin is completely dissolved, and stirring and clathrating for 30min; then cooling to room temperature, adding the formula amount of thioglycerol, adding the rest of water for injection, and stirring and mixing uniformly;
step three: filtering and sterilizing the solution obtained in the step two by a microporous filter membrane with the thickness of 0.22 mu m, thus obtaining the telamycin and vitamin C compound injection.
The content, the tylosin A, B isomer and the pH value of the tylosin compound injection prepared in examples 1-13 are detected, and the results are shown in the following table:
TABLE 1
Figure GDA0004083129340000161
Analysis of the sample detection results of examples 1, 4 and 5 shows that the solubilizing effect of the glucosyl-beta-cyclodextrin on the tulathromycin is better when the weight ratio of the glucosyl-beta-cyclodextrin to the tulathromycin is 1:1; as can be seen from the detection results of the samples in comparative examples 1 and 6-11, the cosolvent is preferably tromethamine and meglumine, and the addition amount of the cosolvent and the meglumine is 3g/L, and the ratio is preferably 2:1; the test results of the samples of comparative examples 1 and 13 show that the stability of tulathromycin and vitamin C is not significantly different from that of the samples without the antioxidant (thioglycerol). To sum up the analysis, the heating temperature and heating time are preferably 60 ℃ for 30min, and the weight ratio of the selected glucosyl-beta-cyclodextrin to the tulathromycin is preferably 1:1.
Example 14: compound telamycin injection
Figure GDA0004083129340000171
The preparation method comprises the following steps: as in example 1.
The test for acceleration and long-term test were carried out using the telapramycin complex injection prepared in example 14 as a sample, and the stability of the telapramycin complex injection was examined. The experimental results are shown in the following tables (tables 2 and 3):
TABLE 2 data for acceleration test (40.+ -. 2 ℃ C.)
Figure GDA0004083129340000172
Figure GDA0004083129340000181
TABLE 3 data for long-term test (25.+ -. 2 ℃ C.)
Figure GDA0004083129340000182
The data (table 2 and table 3) of the accelerated test (40+/-2 ℃) and the long-term test (25+/-2 ℃) show that the characteristics, the pH value and the like of the sample are not obviously changed after the test is placed for 6 months in the accelerated test and the test is placed for 12 months in the long-term test, various quality indexes such as the content of the sample, namely the tulathromycin and the vitamin C are qualified, and the compound injection prepared from the tulathromycin and the glucosyl-beta-cyclodextrin is effectively proved to have good quality stability.
EXAMPLE 15 irritation test
The compound injection of tulathromycin prepared in example 14 was used as a medicine, and compared with the 10% tulathromycin injection preparation (using organic solvent/water as solvent) which has been marketed, neck intramuscular injection was performed on 12 cattle and 6 pigs, respectively, with the administration doses of 2.5mg/kg and 7.5mg/kg, respectively, and the specific cases are shown in tables 4 and 5 below:
TABLE 4 Table 4
Figure GDA0004083129340000183
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Figure GDA0004083129340000191
TABLE 5
Figure GDA0004083129340000192
As can be seen from the results of the irritation experiments of the tulathromycin compound injection prepared by the invention and the 10% tulathromycin injection on the cattle injection site, only one of the 6 cattle and the 3 pigs injected with the preparation 14 has slight pain reaction when the injection dosage is slightly larger, and the rest 5 cattle and the 3 pigs have no injection irritation reaction; for 6 cattle and 3 pigs injected with 10% tulathromycin injection on the market, 5 cattle showed pain reaction, local swelling at the injection site, swelling at the injection site when the dosage was increased, and 2 pigs showed pain reaction, wherein 1 pig showed local swelling at the injection site, and swelling disappeared only after 8 to 33 days. The irritation test result shows that the tulathromycin composite injection prepared by the invention has good tissue compatibility and no obvious irritation.
EXAMPLE 16 blood concentration determination of Talarmycin composite injection
The telapramycin compound injection prepared in example 14 was used as a medicine, and compared with the preparation 1-10% telapramycin injection preparation (organic solvent/water was used as injection solvent) which was marketed, and the preparation 2-10% telapramycin injection preparation (oily solvent was used as injection solvent). 30 healthy pigs are selected, the weight of the pigs is 40-50kg, the pigs are divided into 3 groups, 10 pigs in each group are respectively subjected to neck intramuscular injection, the administration doses are respectively 2.5mg/kg, blood is taken on time, and the tulathromycin content (ng/ml) in blood plasma is detected, wherein the specific conditions are shown in the following table 6:
TABLE 6
Figure GDA0004083129340000201
From comparison of the results of the blood concentration detection after injection of the three preparations in Table 6, the preparation in example 14 reached the peak of the blood concentration faster than the preparation 1 tulathromycin injection preparation (with organic solvent/water as the injection solvent); in the preparation 2, the peak time of the blood concentration is not obviously different when the injection is just injected in the early stage of the tulathromycin injection preparation (taking an oily solvent as an injection solvent), but the preparation of the example 14 still has higher blood concentration in the later 48 hours, and the drug release speed in the body is stable and the concentration is close in 48 hours. In conclusion, the analysis of the results shows that, compared with the injection of the tulathromycin injection preparation 1 (taking the organic solvent/water as the injection solvent) and the tulathromycin injection preparation 2 (taking the oily solvent as the injection solvent), the injection preparation of the tulathromycin preparation 14 has obvious advantages of quick release and slow and controlled release, and simultaneously has the characteristics of complete administration absorption, long half-life and high bioavailability.
Example 17 the treatment effect of the preparation of example 14 was compared with that of the preparations 1 and 2 of example 16, 36 pigs (weight about 50 kg) with clinical symptoms of respiratory diseases in a large pig farm were selected for test, and according to the clinical symptoms (see table 7), the 36 pigs were classified into 3-serious (6 heads), 2-moderate (21 heads) and 1-mild (9 heads) 3 grades, and the 3 grades were divided into 3 groups respectively, the preparation of example 14 was injected into the 1 st group, the preparation of 2 nd injection, the preparation of 3 rd injection 2, and the intramuscular injection in the neck, and the dosage was 2.5mg/kg. Clinical symptoms and recurrence and weight gain after 2 months were observed 1, 2, 5 and 7 days after treatment, and the results are shown in Table 8.
TABLE 7 clinical symptom scoring criteria
Figure GDA0004083129340000211
Table 8 results of grading clinical symptoms
Figure GDA0004083129340000212
Figure GDA0004083129340000221
As can be seen from the data analysis in Table 8, the severe pigs after administration of the preparation of example 14 had all been changed to moderate and mild symptoms on day 3, and the clinical symptoms of all sick pigs had substantially disappeared on day 7; and 1 pig with severe clinical symptoms and 6 pigs with mild symptoms on day 7 after administration of formulation 1; after administration of formulation 2, 5 mild pigs remained on day 7. The data show that the preparation of example 14 has quick response, quick disappearance of symptoms and high bioavailability for pigs suffering from respiratory diseases, and is particularly beneficial to the treatment of severe pigs.
Exterior 9 recurrence of disease and weight increase
Figure GDA0004083129340000222
According to the data analysis of Table 9, after the treatment and cure, the pigs in the preparation group of example 14 have no recurrent respiratory diseases, the pigs in the preparation group of example 14 have 1 recurrent respiratory diseases, and the pigs in the preparation group of example 14 have 3 recurrent respiratory diseases, and the weight gain of the pigs in the preparation group of example 14 is larger than that of the pigs in the preparation group of example 1 and the preparation group of example 2, so that the tulathromycin composite injection is shown to be compared with the tulathromycin injection preparation of which the ratio is 1-10% (taking organic solvent/water as injection solvent) and the tulathromycin injection preparation of which the ratio is 2-10% (taking oily solvent as injection solvent), so that the body recovery of the pigs can be fast, the effect is good, and the immunity of the pigs can be enhanced.
In the present specification, each embodiment is described in a progressive manner, and each embodiment is mainly described in a different point from other embodiments, and identical and similar parts between the embodiments are all enough to refer to each other.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to the embodiments described above will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (7)

1. The tulathromycin composite injection is characterized by comprising the following components: the tulathromycin, the vitamin C, the solubilizer and the cosolvent, the rest is solvent, the solubilizer is glucosyl-beta-cyclodextrin, the cosolvent is one or two of meglumine, tromethamine or nicotinamide,
the specific component content is as follows:
100g/L of tulathromycin;
vitamin C100 g/L;
80-130g/L of solubilizer;
2-8g/L of cosolvent;
the balance being solvent.
2. The tulathromycin composite injection of claim 1, wherein the weight ratio of the glucosyl-beta-cyclodextrin to tulathromycin is 1:1.
3. The tulathromycin composite injection according to claim 1, wherein the content of the cosolvent component is 3-5g/L.
4. A method for preparing a telapramycin compound injection according to any one of claims 1-3, characterized by comprising the following steps:
step one: taking a solvent accounting for 90% of the total amount, introducing nitrogen into the solvent, adding a solubilizer and a cosolvent, and stirring for dissolution; adding vitamin C, stirring and dissolving completely, wherein the pH value of the solution is 1.3-1.8;
step two: slowly adding tulathromycin into the solution obtained in the step one, heating until the tulathromycin is dissolved, and stirring and clathrating the tulathromycin for 30-120 min; adding the rest solvent, and stirring and mixing uniformly;
step three: and (3) sterilizing and filtering the solution obtained in the step two to obtain the tulathromycin and vitamin C compound injection, wherein the pH value of the injection is 5.0-5.5.
5. The method for preparing a telamycin compound injection according to claim 4, wherein in the second step, the inclusion time is 30-40 min.
6. The method for preparing a telamycin compound injection according to claim 4, wherein in the second step, the temperature is 50-60 ℃.
7. The method for preparing a telapramycin compound injection according to claim 4, wherein in the third step, the pH value is 5.2.
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