Movatterモバイル変換


[0]ホーム

URL:


CN116459268B - Solution composition containing tilmicosin and preparation method thereof - Google Patents

Solution composition containing tilmicosin and preparation method thereof
Download PDF

Info

Publication number
CN116459268B
CN116459268BCN202310344523.7ACN202310344523ACN116459268BCN 116459268 BCN116459268 BCN 116459268BCN 202310344523 ACN202310344523 ACN 202310344523ACN 116459268 BCN116459268 BCN 116459268B
Authority
CN
China
Prior art keywords
tilmicosin
parts
citric acid
polysorbate
ethanol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202310344523.7A
Other languages
Chinese (zh)
Other versions
CN116459268A (en
Inventor
许天罡
李斌
江善祥
邓锐涵
王东明
李万勇
张洁
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zibo Wellcell Biotechnology Co ltd
Original Assignee
Zibo Wellcell Biotechnology Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zibo Wellcell Biotechnology Co ltdfiledCriticalZibo Wellcell Biotechnology Co ltd
Priority to CN202310344523.7ApriorityCriticalpatent/CN116459268B/en
Publication of CN116459268ApublicationCriticalpatent/CN116459268A/en
Application grantedgrantedCritical
Publication of CN116459268BpublicationCriticalpatent/CN116459268B/en
Activelegal-statusCriticalCurrent
Anticipated expirationlegal-statusCritical

Links

Classifications

Landscapes

Abstract

The invention provides a solution composition containing tilmicosin and a preparation method thereof, and belongs to the technical field of veterinary medicines, wherein the solution composition comprises the following raw materials: tilmicosin, eucalyptus oil, polysorbate, citric acid, ethanol and distilled water; the preparation method of the solution composition comprises the following steps: sieving tilmicosin and citric acid for standby; taking corresponding parts by weight of distilled water, polysorbate, citric acid, ethanol and tilmicosin, uniformly mixing, then adding eucalyptus oil, and uniformly mixing to obtain a composition; the solution composition provided by the invention has the advantages of good stability, good palatability, convenient drinking water administration, obvious effect of treating mycoplasma infection of livestock and poultry, good oral absorption and high safety.

Description

Solution composition containing tilmicosin and preparation method thereof
Technical Field
The invention belongs to the technical field of veterinary medicines, and particularly relates to a solution composition containing tilmicosin and a preparation method thereof.
Background
Respiratory diseases are always limiting the development of livestock breeding industry in China. Especially, along with the economic development, the consumption level of people is improved, the requirements on the health and safety of foods are continuously improved, the traditional cultivation is changed into large-scale cultivation and intensive cultivation, and the cultivation quantity is greatly increased. Although the national industry system is continuously perfect and sound, the problems of history carry-over and antibiotics abuse and the like lead the incidence rate of respiratory diseases in livestock and poultry cultivation to be high, the cultivation cost to be continuously increased, and the method is an pain spot which is not solved by the cultivation industry in China.
Mycoplasma, a class of minimal prokaryotic type microorganisms that have no cell wall, are highly polymorphic, and are 0.1-0.3 microns in size. After mycoplasma infection, the mycoplasma is mainly attached to cilium cells of the airway epithelium, so that cilium activities are reduced, antibacterial mucus is reduced, and the organism generates airway symptoms; moreover, the probability of invasion of other pathogenic microorganisms into organisms is increased, and mixed infection of other bacteria such as colibacillosis and viruses is extremely easy to occur in mycoplasma-pathogenic chicken mycoplasmosis, mycoplasma synoviae disease, mycoplasma hyopneumoniae and the like, so that prevention and treatment of mycoplasma infection is a serious issue in cultivation.
Tilmicosin belongs to a semisynthetic macrolide antibacterial agent special for animals, has an antibacterial effect similar to tylosin, and sensitive gram-positive bacteria such as staphylococcus aureus (including penicillin-resistant staphylococcus aureus), pneumococcus, streptococcus and the like. Sensitive gram-negative bacteria include haemophilus and pasteurella, and are also effective against mycoplasma. Has stronger activity on mycoplasma avium than tylosin. However, the application range is affected by the defects of poor palatability, poor water solubility, cardiotoxicity caused by injection administration and the like, and generally, the phosphate is used for improving the water solubility and is more used on poultry.
The eucalyptus oil can inhibit the synthesis of epoxidase (inflammatory substance denoprostone synthesis rate-limiting enzyme), thereby preventing the release of inflammatory reaction medium, inhibiting the generation and secretion of mucus, exhibiting anti-inflammatory properties, promoting the regeneration of airway epithelial cells, especially the regeneration of cilia in the trachea, and preventing the entry of particulate matter and pathogens into the lower airway; relieving inflammation and cough, relieving respiratory tract symptoms, diluting sputum in respiratory tract, accelerating cilia swing, and promoting sputum discharge.
In the prior art, the problems of poor water solubility, poor palatability, easy degradation and low bioavailability of tilmicosin exist, and stable tilmicosin solution products are difficult to prepare.
The Chinese patent document CN107998265A (application number: 201810037522.7) discloses a Chinese and western medicine compound oral liquid for treating porcine respiratory diseases, a preparation method and application thereof, and the preparation method of the Chinese and western medicine compound oral liquid comprises the following steps: dissolving folium Eriobotryae extract, bulbus Fritillariae Cirrhosae extract, tilmicosin phosphate, mentholum, essence, sucrose and adjuvants, and sterilizing. Chinese patent document CN114796108a (application number: 202210753943.6) discloses a tilmicosin solution and a preparation method thereof, the tilmicosin solution is prepared from the following raw materials in parts by weight: 1 to 2 parts of hydroxypropyl methylcellulose, 0.1 to 0.2 part of raw material A, 8 to 12 parts of tilmicosin and a proper amount of purified water; wherein the viscosity of the hypromellose is 3 mPa.s-2000 mPa.s; the raw material A is one of sodium alginate, alginic acid sulfate and fucoidan sodium diester. Chinese patent document CN112516085A (application number: 202011334422.4) discloses a tilmicosin solution, a preparation method and a use method thereof, wherein the tilmicosin solution comprises the following raw materials in percentage by weight: 10 to 50 percent of tilmicosin, 4 to 10 percent of mixture, 1 to 3 percent of solubilizer, 8 to 15 percent of emulsifier, 2 to 5 percent of auxiliary emulsifier, 1 to 3 percent of flavoring agent, 0.5 to 2 percent of taste blocking agent, 8 to 20 percent of oil phase substance and the balance of water; the emulsifier consists of a natural emulsifier and a nonionic surfactant. The tilmicosin solution product disclosed in the prior art is obviously different from the technical scheme of the invention.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a solution composition containing tilmicosin and a preparation method thereof.
The invention develops a novel tilmicosin composition product with obvious effect on mycoplasma infection, long-acting stability and good palatability, and is suitable for popularization and application in livestock breeding industry.
The technical scheme of the invention is as follows:
A solution composition containing tilmicosin comprises the following raw materials: tilmicosin, eucalyptus oil, polysorbate, citric acid, ethanol and distilled water.
According to the invention, the solution composition comprises the following raw materials in 100 parts by weight: 10-25 parts of tilmicosin, 5-30 parts of eucalyptus oil, 10-20 parts of polysorbate, 1-3 parts of citric acid, 15-30 parts of ethanol and the balance of distilled water.
According to a preferred embodiment of the invention, the polysorbate is polysorbate 80.
The preparation method of the tilmicosin-containing solution composition comprises the following steps:
(1) Sieving tilmicosin and citric acid for standby;
(2) Taking corresponding parts by weight of distilled water, polysorbate, citric acid, ethanol and tilmicosin, uniformly mixing, then adding eucalyptus oil, and uniformly mixing to obtain the composition.
According to a preferred embodiment of the present invention, in step (1), tilmicosin is sieved through a 80 mesh sieve and citric acid is sieved through a 200 mesh sieve.
According to the invention, in the step (2), the tilmicosin, polysorbate and citric acid which are corresponding weight parts are taken, placed into a mixed solution of ethanol and distilled water, uniformly mixed, and then eucalyptus oil is added to uniformly mix, so that the composition is prepared.
According to a preferred embodiment of the present invention, in the step (2), the polysorbate is polysorbate 80.
Advantageous effects
1. The tilmicosin-containing solution composition provided by the invention has good stability in the product stability investigation period; in the water solution simulating the water blending amount for clinical use, the stability is good within 48 hours, the degradation rate is low, and the clinical application is convenient.
2. The tilmicosin-containing solution composition provided by the invention has obvious effect of treating mycoplasma infection of livestock and poultry, good oral absorption, high safety and stable effect.
3. The tilmicosin-containing solution composition provided by the invention is simple in preparation method and beneficial to popularization and application.
Drawings
FIG. 1 is a graph showing the variation of tilmicosin content in aqueous solutions for preparing compositions of examples 1-3.
FIG. 2 is a graph showing the variation of tilmicosin content in aqueous solutions of compositions prepared in comparative examples 1-7.
FIG. 3 is a liquid chromatogram of tilmicosin content of the composition prepared in example 1 stored for 2 months.
FIG. 4 is a liquid chromatogram of tilmicosin content when the composition prepared in comparative example 1 was stored for 1 month.
FIG. 5 is a liquid chromatogram of tilmicosin content in an aqueous solution at 0h of the composition prepared in example 1.
Fig. 6 is a liquid chromatogram of tilmicosin standard.
Detailed Description
The invention is further described below with reference to the drawings and the specific embodiments, but the scope of the invention is not limited thereto.
The drugs and reagents used in the examples are common products on the market unless otherwise specified, and the details not specifically described in the examples are all in accordance with the prior art.
Example 1
A solution composition containing tilmicosin, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 5 parts of eucalyptus oil, 80 parts of polysorbate, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The preparation method of the tilmicosin-containing solution composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with 80 mesh sieve for standby, and sieving citric acid with 200 mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin with the formula amount, the polysorbate 80 with the formula amount and the citric acid with the formula amount into a mixed solution of ethanol with the formula amount and distilled water with the formula amount, stirring, adding eucalyptus oil with the formula amount after the tilmicosin is dissolved until the tilmicosin is clarified, and stirring until the tilmicosin is clarified, thus obtaining the composition.
Example 2
A solution composition containing tilmicosin, which comprises the following raw materials in 100 parts by weight: 25 parts of tilmicosin, 15 parts of eucalyptus oil, 15 parts of polysorbate, 3 parts of citric acid, 30 parts of ethanol and the balance of distilled water.
The preparation method of the tilmicosin-containing solution composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with an 80-mesh sieve for standby, and sieving citric acid with a 200-mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin with the formula amount, the polysorbate 80 with the formula amount and the citric acid with the formula amount into a mixed solution of ethanol with the formula amount and distilled water with the formula amount, stirring, adding eucalyptus oil with the formula amount after the tilmicosin is dissolved until the tilmicosin is clarified, and stirring until the tilmicosin is clarified, thus obtaining the composition.
Example 3
A solution composition containing tilmicosin, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 30 parts of eucalyptus oil, 20 parts of polysorbate, 1 part of citric acid, 20 parts of ethanol and the balance of distilled water.
The preparation method of the tilmicosin-containing solution composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with an 80-mesh sieve for standby, and sieving citric acid with a 200-mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin with the formula amount, the polysorbate 80 with the formula amount and the citric acid with the formula amount into a mixed solution of ethanol with the formula amount and distilled water with the formula amount, stirring, adding eucalyptus oil with the formula amount after the tilmicosin is dissolved until the tilmicosin is clarified, and stirring until the tilmicosin is clarified, thus obtaining the composition.
Comparative example 1
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 2.5 parts of eucalyptus oil, 2.5 parts of peppermint essential oil, 80 parts of polysorbate, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that 2.5 parts of eucalyptus oil, 2.5 parts of peppermint essential oil are all the same.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with an 80-mesh sieve for standby, and sieving citric acid with a 200-mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin, polysorbate 80 and citric acid in a mixed solution of ethanol and distilled water in a formula amount, stirring, adding eucalyptus oil and peppermint essential oil in the formula amount after the tilmicosin is dissolved until the tilmicosin is clarified, and stirring until the tilmicosin is clarified, thus obtaining the composition.
Comparative example 2
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 5 parts of mint essential oil, 80 parts of polysorbate, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that the eucalyptus oil is 0 part, the peppermint essential oil is 5 parts, and the other parts are the same.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with an 80-mesh sieve for standby, and sieving citric acid with a 200-mesh sieve for standby;
(2) Dissolving: and (3) taking the formula amount of tilmicosin, the formula amount of polysorbate 80 and the formula amount of citric acid, placing the tilmicosin, the formula amount of polysorbate 80 and the formula amount of citric acid into a mixed solution of the formula amount of ethanol and the formula amount of distilled water, stirring, adding the formula amount of peppermint essential oil after the tilmicosin is dissolved until the tilmicosin is clarified, and stirring until the tilmicosin is clarified, thus obtaining the composition.
Comparative example 3
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 5 parts of eucalyptus oil, 5 parts of polysorbate, 5 parts of polyoxyethylene castor oil, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that the polysorbate is 5 parts, the polyoxyethylated castor oil is 5 parts, all other things being equal.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with an 80-mesh sieve for standby, and sieving citric acid with a 200-mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin, the polysorbate 80, the polyoxyethylene castor oil and the citric acid in a mixed solution of the ethanol and the distilled water in the formula amount, stirring, adding the eucalyptus oil in the formula amount after the tilmicosin is dissolved until the tilmicosin is clarified, and stirring until the tilmicosin is clarified, thus obtaining the composition.
Comparative example 4
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 5 parts of eucalyptus oil, 10 parts of polyoxyethylene castor oil, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that polysorbate 80 parts, polyoxyethylated castor oil 10 parts, all other things being equal.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with an 80-mesh sieve for standby, and sieving citric acid with a 200-mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin, the polyoxyethylene castor oil and the citric acid in the formula amount into a mixed solution of the ethanol in the formula amount and the distilled water in the formula amount, stirring, adding the eucalyptus oil in the formula amount after the tilmicosin is dissolved until the tilmicosin is clarified, and stirring until the tilmicosin is clarified, thus obtaining the composition.
Comparative example 5
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 32 parts of eucalyptus oil, 8010 parts of polysorbate, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that 32 parts of eucalyptus oil are identical to each other.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with 80 mesh sieve for standby, and sieving citric acid with 200 mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin with the formula amount, the polysorbate 80 with the formula amount and the citric acid with the formula amount into a mixed solution of ethanol with the formula amount and distilled water with the formula amount, stirring, adding eucalyptus oil with the formula amount after the tilmicosin is dissolved until the tilmicosin is clarified, and stirring until the tilmicosin is clarified, thus obtaining the composition.
Comparative example 6
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 3 parts of eucalyptus oil, 80 parts of polysorbate, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that 3 parts of eucalyptus oil are identical to each other.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with 80 mesh sieve for standby, and sieving citric acid with 200 mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin with the formula amount, the polysorbate 80 with the formula amount and the citric acid with the formula amount into a mixed solution of ethanol with the formula amount and distilled water with the formula amount, stirring, adding eucalyptus oil with the formula amount after the tilmicosin is dissolved until the tilmicosin is clarified, and stirring until the tilmicosin is clarified, thus obtaining the composition.
Comparative example 7
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 80 parts of polysorbate, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that the eucalyptus oil is 0 part, all other things being equal.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with 80 mesh sieve for standby, and sieving citric acid with 200 mesh sieve for standby;
(2) Dissolving: and (3) taking the formula amount of tilmicosin, the formula amount of polysorbate 80 and the formula amount of citric acid, placing the tilmicosin, the formula amount of polysorbate 80 and the formula amount of citric acid into a mixed solution of the formula amount of ethanol and the formula amount of distilled water, stirring, and obtaining the composition after the tilmicosin is dissolved until the tilmicosin is clear.
Comparative example 8
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 5 parts of eucalyptus oil, 80 parts of polysorbate, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that the polysorbate 80 is 23 parts, all other things being equal.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with 80 mesh sieve for standby, and sieving citric acid with 200 mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin, polysorbate 80 and citric acid in a mixed solution of ethanol and distilled water in a formula amount, stirring, adding eucalyptus oil in a formula amount after the tilmicosin is dissolved to be clear, and stirring until turbidity is not clear.
Therefore, when polysorbate 80 is used in excess of parts by weight, a uniform and stable clear solution cannot be obtained.
Comparative example 9
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 5 parts of eucalyptus oil, 5 parts of polysorbate, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that the polysorbate 80 is 5 parts, all other things being equal.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with 80 mesh sieve for standby, and sieving citric acid with 200 mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin, polysorbate 80 and citric acid in a mixed solution of ethanol and distilled water in a formula amount, stirring, adding eucalyptus oil in a formula amount after the tilmicosin is dissolved until the tilmicosin is clear, and stirring until the solution is slightly turbid and not clear.
Therefore, when polysorbate 80 is used below parts by weight, a uniform and stable clear solution cannot be obtained.
Comparative example 10
A composition, which comprises the following raw materials in 100 parts by weight: 10 parts of tilmicosin, 5 parts of eucalyptus oil, 1 part of citric acid, 15 parts of ethanol and the balance of distilled water.
The difference from example 1 is that the polysorbate 80 is 0 part, all other things being equal.
The preparation method of the composition comprises the following steps:
(1) Sieving: sieving tilmicosin in the formula with 80 mesh sieve for standby, and sieving citric acid with 200 mesh sieve for standby;
(2) Dissolving: and (3) placing the tilmicosin with the formula amount and the citric acid with the formula amount into a mixed solution of ethanol with the formula amount and distilled water with the formula amount, stirring, adding the eucalyptus oil with the formula amount after the tilmicosin is dissolved until the tilmicosin is clarified, stirring until the tilmicosin is slightly turbid, and standing until layering occurs.
Thus, when the present invention rejects polysorbate 80, a uniform and stable clear solution is not obtained.
Effect example
Test example 1 stability test of inventive and comparative preparation compositions
Test samples prepared in examples 1-3 and samples prepared in comparative examples 1-7 were selected, marketed package (oral liquid pharmaceutical high density polyethylene bottle) was simulated, stored for 6 months in an environment of 40 ℃ ± 2 ℃ and RH25% ± 5%, sampled at the end of the 0 th, 1,2,3 and 6 months of the test period, and the tilmicosin content was detected (according to the classical veterinary drug standard, the limit of detection was 90% -110% of the indicated amount), and compared with the detection result of the 0 th month, and the results are shown in table 1.
TABLE 1 stability test results for compositions prepared in examples and comparative examples of the present invention
Note that: tilmicosin content is a percentage of the indicated amount.
As is clear from Table 1, the degradation rates of examples 1 to 3 were 3.8%, 3.7% and 3.8% respectively, and the degradation rates of comparative examples 1 to 7 were 6.8%, 7.8%, 6.5%, 7.3%, 8.7%, 8.4% and 9.0% respectively, although the detection results at month 6 were all within the limits of the detection limit. According to the technical guidelines of research on the stability of veterinary chemical drugs, the content of the samples in examples 1-3 is not more than 5%, and the stability is good; the content of the samples in comparative examples 1-7 is changed by more than 5%, and the stability is not qualified.
The composition prepared in example 1 is stored for 2 months, and a liquid chromatogram of tilmicosin content is shown in fig. 3; the composition prepared in comparative example 1 is stored for 1 month, and a liquid chromatogram of tilmicosin content is shown in fig. 4; the liquid chromatogram of tilmicosin standard is shown in figure 6.
Test example 2 stability test of aqueous solutions of the compositions prepared in examples and comparative examples of the present invention
The samples prepared in examples 1-3 and the samples prepared in comparative examples 1-7 were selected for aqueous solution stability test; examples 1,3 and comparative examples 1 to 7 were dissolved in 500ml of purified water respectively according to the water addition amount of 0.75ml/L, example 2 was dissolved in 0.3ml/L of purified water respectively, the samples were taken as the 0 th hour after mixing, and then the samples were taken from the top and bottom of the standing solution at the 1 st hour, 2h, 3h, 6h, 12h, 24h and 48h respectively, and the tilmicosin content was measured, and the results were shown in FIG. 1 and FIG. 2; the degradation rate of 48h compared with 0h was calculated and the results are shown in Table 2.
TABLE 2 results of 48h degradation rate in aqueous solution stability test of compositions prepared in examples and comparative examples of the present invention
Note that:*(P<0.05),** (P < 0.01) compared to group 0 h;(P<0.05),△△ (P < 0.01) was compared to the same set of 48h top sampling points.
As can be seen from fig. 1 and 2, the comparative examples 1 to 7 have a large variation in tilmicosin degradation rate as compared with the examples 1 to 3.
As can be seen from Table 2, there was no significant difference (p > 0.05) between the top and bottom contents of the groups of examples 1 to 3, indicating that the aqueous solutions of the groups of examples 1 to 3 were uniform and stable for 48 hours. Compared with 0h, 48h shows that the degradation rates of the different sampling points of the tilmicosin content groups of examples 1-3 are all within 0.5%, and have no significant difference (p > 0.05), and the degradation rates of the different sampling points of the comparison examples 1-7 are all above 2%, and have significant difference (p < 0.05) or very significant difference (p < 0.01). Therefore, the aqueous solutions of examples 1 to 3 are stable within 48 hours compared with the aqueous solutions of comparative examples 1 to 7, are convenient for clinical application, and are suitable for popularization.
The composition prepared in example 1 has a liquid chromatogram of tilmicosin content in the aqueous solution at 0h as shown in FIG. 5; the liquid chromatogram of tilmicosin standard is shown in figure 6.
Test example 3 comparative test of the effects of the compositions prepared in the examples and comparative examples of the present invention on treatment of Mycoplasma gallisepticum
Test the samples prepared in examples 1-3 and comparative examples 1-7 were selected for testing.
The approximately diseased chickens were selected from the 10-day-old diseased chicken flocks naturally infected with mycoplasma gallisepticum, and randomly divided into a blank control group, an example 1 group, an example 2 group, an example 3 group, a comparative example 1 group, a comparative example 2 group, a comparative example 3 group, a comparative example 4 group, a comparative example 5 group, a comparative example 6 group and a comparative example 7 group, 100 healthy same-day-old breeds of chickens were selected as negative control groups, and the groups of chickens were bred under the same conditions in a mutually isolated manner, and the negative control groups were bred by a single person. The negative control group and the blank control group were each daily given clean tap water, and the other examples and comparative examples were given in the following amounts: the free drinking water of the dosage of 0.75ml/L is adopted in the groups of the examples 1 and 3, the free drinking water of the dosage of 0.3ml/L is adopted in the group of the example 2, and the free drinking water of the dosage of 0.75ml/L is adopted in the groups of the comparative examples 1 to 7 (the dosage of each group is calculated by tilmicosin, and the dosage is the same as that of the example 1). Other similar medicines are forbidden during the administration period, the administration is continued for 3 days, the administration is stopped, the observation is carried out for 5 days, the conditions of each group of chickens are observed every day, and the recorded results are shown in Table 3.
Curative effect judgment criteria:
Invalidation: symptoms such as cough, depression, open mouth, wheeze, decreased appetite, tracheal rales, runny nose, eyelid swelling, conjunctival congestion, etc., and are more serious than before treatment; dead animals were counted as invalid;
The method is effective: the respiratory symptoms of the affected chickens are relieved compared with those before treatment, the respiratory symptoms are weak, the diet is gradually recovered, and the spirit and the activity are improved;
the effect is shown: the respiratory symptoms of the sick chickens are obviously relieved to disappear, the air flow is smooth during breathing, the sound is obviously relieved, the diet, the activity and the spirit are basically recovered, and the manifestation is active;
And (3) curing: the diet and activity of the affected chickens are not different from those of healthy chickens, and symptoms completely disappear;
The total effective rate calculation formula:
total effective rate= (cure number + significant number + effective number)/total number 100%.
TABLE 3 results of comparative experiments on the effects of compositions prepared in examples and comparative examples of the present invention on treatment of Mycoplasma gallisepticum
As can be seen from Table 3, the total effective rate of the group of example 1 was 97%; the total effective rate of the group of the example 2 is 96%; the total effective rate of the group of the example 3 is 96%; the total effective rate of comparative example 1 is 71%; comparative example 2 has a total effective rate of 66%; comparative example 3 has a total effective rate of 70%; comparative example 4 has a total effective rate of 62%; comparative example 5 has a total effective rate of 79%; comparative example 6 has a total effective rate of 70%; comparative example 7 has a total effective rate of 63%; the total effective rate of the blank group is 23% (self-healing).
As can be seen from the results in Table 3, the tilmicosin-containing solution composition provided by the invention has a far better effect on treating mycoplasma gallisepticum infection than other comparative examples.
Test example 4 comparative test of the effect of compositions prepared in examples and comparative examples of the present invention on treatment of mycoplasma hyopneumoniae infection
Test the samples prepared in examples 1-3 and comparative examples 1-7 were selected for testing.
The approximately diseased pigs 220 are selected from naturally infected pigs with mycoplasma and with age 5 months, randomly divided into blank control groups, example 1 groups, example 2 groups, example 3 groups, comparative example 1 groups, comparative example 2 groups, comparative example 3 groups, comparative example 4 groups, comparative example 5 groups, comparative example 6 groups and comparative example 7 groups, 20 healthy pigs with age 20 are selected as negative control groups, and the groups are fed under the same condition, mutually isolated and fed by a single person. The negative control group and the blank control group were not administered, and the groups of examples 1 and 3 were fed manually at a dose of 12 ml/head per day, the group of example 2 was fed manually at a dose of 4.8 ml/head per day, and the groups of comparative examples 1 to 7 were fed manually at a dose of 12 ml/head per day (the amounts of the groups were calculated as tilmicosin and the same as the amount of example 1). Other similar drugs were disabled during the administration period, and the administration was continued for 7 days, and after the withdrawal, the administration was observed for 7 days, and each group of conditions was observed and recorded every day, and the results are shown in table 4.
Curative effect judgment criteria:
The body temperature and appetite of the pig group after infection of mycoplasma hyopneumoniae have no obvious change. The early stage of the disease is mainly characterized by continuous dry cough, asthma and dyspnea (the pig breathes in abdomen) in middle and later stages, rapid emaciation, mild cyanosis of eyelids, nose ends, upper and lower lips, edema and congestion of few pig eyelids, bluish violet blood stasis spots at the root of the ear and the edge of auricle, and extremely emaciation in part and shivering of the back of the bow.
Invalidation: continuous dry cough, asthma, dyspnea (pig breathes in abdominal form), emaciation, slight cyanosis of eyelids, nose ends, upper and lower lips, eyelid edema congestion, blue-violet blood stasis spots on the root of ear and the edge of auricle, shivering of the back of the bow and other symptoms, and are serious before treatment; dead animals were counted as invalid;
the method is effective: compared with the prior treatment, the respiratory symptoms of the sick pigs are relieved, the asthma is weakened, the cyanosis and blood spots are not aggravated any more, and the spirit is improved;
The effect is shown: the symptoms of the respiratory tract of the sick pigs disappear, the air flow is smooth during breathing, the conditions of cyanosis and blood spots are obviously lightened, and the activities and the spirit are basically recovered;
and (3) curing: the diet and activity of the sick pigs are indiscriminate from those of healthy pigs, and symptoms completely disappear;
The total effective rate calculation formula:
total effective rate= (cure number + significant number + effective number)/total number 100%.
TABLE 4 results of comparative experiments on the effect of compositions prepared in examples and comparative examples of the present invention on treatment of mycoplasma infection in swine
Group ofQuantity (head)Cure (head)Display effect (head)Effective (head)Invalidation (head)Total effective rate (%)
Example 1 group2015230100
Example 2 group201432195
Example 3 group2016220100
Comparative example 1 group20653670
Comparative example 2 group20526765
Comparative example 3 group20842670
Comparative example 4 group20624860
Comparative example 5 group20745480
Comparative example 6 group20644670
Comparative example 7 group20526765
Blank control group20003 (Self-healing)1715
Negative control group20——————————
As can be seen from table 4, the total effective rate of the group of example 1 is 100%; the total effective rate of the group of the example 2 is 95%; the total effective rate of the group of the example 3 is 100%; the total effective rate of comparative example 1 is 70%; the total effective rate of comparative example 2 is 65%; comparative example 3 has a total effective rate of 70%; comparative example 4 has a total effective rate of 60%; comparative example 5 has a total effective rate of 80%; comparative example 6 has a total effective rate of 70%; comparative example 7 has a total effective rate of 65%; the total effective rate of the blank group is 15% (self-healing).
The results show that the effect of the solution composition containing tilmicosin for treating mycoplasma infection of pigs is far better than that of other comparative example groups.
Test example 5 palatability test of compositions prepared in examples and comparative examples of the present invention to pigs
Test the samples prepared in example 1 were selected for testing with the samples prepared in comparative example 7.
Selecting a pig farm fattening pig in Shandong province as a test object, selecting 60 test pigs with similar development states, wherein the weight of each test pig is 60-70 kg, randomly dividing the test pigs into 3 groups of 20 pigs, and feeding each group under the same condition. Example 1 group water was mixed in an amount of 1.5ml/L water; comparative example 7 group was mixed with water in an amount of 1.5ml/L water; the blank control group was not added with medicine, and each group was restricted in total water intake by 10L, and the water intake time was observed, and the results are shown in Table 5.
Table 5 palatability test results of compositions prepared in examples and comparative examples of the present invention to pigs
Group ofTime (h) required for drinking 10L of water
Example 1 group19.2
Comparative example 7 group37.5
Blank control group19.5
The results show that the invention does not enable the taste-sensitive pigs to reduce the water intake, and the group of the embodiment 1 added with eucalyptus oil has less time than the blank control group and good palatability; in the group of comparative example 7, to which eucalyptus oil was not added, the water intake of pigs was much smaller than that of the blank group. Therefore, the eucalyptus oil can be used as a flavoring agent for tilmicosin with poor palatability.
The tilmicosin-containing solution composition provided by the invention has the advantages of good stability, good palatability, convenient drinking water administration, obvious effect on treating mycoplasma infection of livestock and poultry, good oral absorption and high safety. The tilmicosin-containing solution composition provided by the invention is simple in preparation method and beneficial to popularization and application.

Claims (4)

CN202310344523.7A2023-03-292023-03-29Solution composition containing tilmicosin and preparation method thereofActiveCN116459268B (en)

Priority Applications (1)

Application NumberPriority DateFiling DateTitle
CN202310344523.7ACN116459268B (en)2023-03-292023-03-29Solution composition containing tilmicosin and preparation method thereof

Applications Claiming Priority (1)

Application NumberPriority DateFiling DateTitle
CN202310344523.7ACN116459268B (en)2023-03-292023-03-29Solution composition containing tilmicosin and preparation method thereof

Publications (2)

Publication NumberPublication Date
CN116459268A CN116459268A (en)2023-07-21
CN116459268Btrue CN116459268B (en)2024-09-20

Family

ID=87183474

Family Applications (1)

Application NumberTitlePriority DateFiling Date
CN202310344523.7AActiveCN116459268B (en)2023-03-292023-03-29Solution composition containing tilmicosin and preparation method thereof

Country Status (1)

CountryLink
CN (1)CN116459268B (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
CN102512358A (en)*2011-12-162012-06-27南京农业大学Rifaximin vaginal suppository for livestock and preparation method for same
CN104208160A (en)*2014-08-012014-12-17中国人民解放军军事医学科学院放射与辐射医学研究所Application of tea tree oil in treatment of animal bacterial pneumonia

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
DE10107659B4 (en)*2001-02-192008-03-13Lts Lohmann Therapie-Systeme Ag Mucoadhesive disintegratable drug preparation for drug administration in veterinary and human medicine
WO2003105810A1 (en)*2002-06-142003-12-24Andrx CorporationPharmaceutical compositions for drugs having ph-dependentsolubility
CN106729720A (en)*2016-12-272017-05-31佛山市正典生物技术有限公司A kind of composition of Tilmicosin and plants essential oil
CN107929394B (en)*2018-01-172021-01-26信阳农林学院 An oral solid self-emulsifying dispersion for treating respiratory diseases of livestock and poultry
CN112022902A (en)*2019-05-182020-12-04云南伦扬科技有限公司Preparation method and application of carbon-point modified fluconazole eucalyptus oil microemulsion gel
CN113521161A (en)*2020-04-162021-10-22三捷生物科技(北京)有限公司Pharmaceutical composition with function of resisting microbial infection and application thereof
CN112516085B (en)*2020-11-252023-04-07佛山市正典生物技术有限公司Tilmicosin solution and preparation method and use method thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
CN102512358A (en)*2011-12-162012-06-27南京农业大学Rifaximin vaginal suppository for livestock and preparation method for same
CN104208160A (en)*2014-08-012014-12-17中国人民解放军军事医学科学院放射与辐射医学研究所Application of tea tree oil in treatment of animal bacterial pneumonia

Also Published As

Publication numberPublication date
CN116459268A (en)2023-07-21

Similar Documents

PublicationPublication DateTitle
CN101953784B (en) Veterinary suspension containing amoxicillin, colistin sulfate and prednisolone and preparation method thereof
CN102188422B (en)Compound florfenicol injection and preparation method and application thereof
CN101897800B (en) Traditional Chinese Medicine Oral Liquid for Treating Mycoplasma Gallisepticum Infection
CN106667915B (en) A kind of baicalin aluminum dry suspension for treating piglet diarrhea
CN116459268B (en)Solution composition containing tilmicosin and preparation method thereof
CN103211818B (en)Pharmaceutical composition for treating or preventing bacterial and mycoplasma diseases of livestock and use thereof
CN104586777B (en) Ceftiofur hydrochloride powder injection and its preparation method and application
CN104208062A (en)High-concentration compound florfenicol injection, and preparation method and application thereof
CN111759854A (en)Injection composition for treating respiratory diseases of animals and preparation method thereof
CN111603475A (en) A kind of long-acting compound tediloxine injection and preparation method thereof
CN106620668A (en)Compound tilmicosin solid dispersing agent and preparation method thereof
CN111905058A (en)Pharmaceutical composition for skin mucosa nursing and wound repair and preparation method thereof
CN108653205A (en)A kind of long stable effect compound tilmicosin solution and its preparation process
CN104586875A (en)Preparation method for compound tilmicosin enteric-coated granules
CN111228454B (en)A Chinese medicinal aerosol for treating upper respiratory diseases of fowl, and its preparation method
CN115645390A (en)Preparation of valnemulin organic acid salt veterinary drug and application of valnemulin organic acid salt veterinary drug in preparation of drugs for treating poultry air sacculitis and pig pleuropneumonia
CN111568861A (en)Bromhexine hydrochloride oral liquid for livestock and poultry as well as preparation method and application thereof
CN115444074A (en) A kind of quercetin compound traditional Chinese medicine feed additive and its preparation method and application
CN108671000B (en)Compound medicament and application thereof
CN108969648B (en)Pharmaceutical composition and application method thereof
CN112843011A (en)Tilmicosin premix and preparation method thereof
CN113876930B (en) A compound medicine for preventing and treating blue ear disease in pigs
LU505637B1 (en)Medicinal healthcare composition for improving allergy and chronic inflammation and a preparation method thereof
CN109568428B (en)Yongquan plaster for children
CN113057979A (en)Method for producing and preparing Bufo bufo gargarizans granule, prepared Bufo bufo gargarizans granule and application

Legal Events

DateCodeTitleDescription
PB01Publication
PB01Publication
SE01Entry into force of request for substantive examination
SE01Entry into force of request for substantive examination
GR01Patent grant
GR01Patent grant

[8]ページ先頭

©2009-2025 Movatter.jp