Tiamulin ketoprofen injection and preparation method thereof

Abstract

The application discloses a teramycin ketoprofen injection and a preparation method thereof, and belongs to the field of veterinary injections, and is characterized by the following formula components: teramycin, ketoprofen, a catalytic factor, an antioxidant and an injection solvent; the catalytic factor is a polyamide amine dendrimer; and the antioxidant is a mixture of one or more than two of thio-glycerol, sodium metabisulfite or sodium bisulfite. The application has the beneficial effects that the teramycin and the ketoprofen are used in combination, no pH regulator is needed after the polyamide amine dendrimer is added, and an aqueous injection is obtained by the combination of the two, has a rapid effect, is rapidly absorbed after administration, has a short action time, can play a synergistic role in sterilization and inflammation, can not only increase the curative effect of a single drug, but also improve the drug stability and the bioavailability.

Description

Technical fields:

[0001] This invention relates to the field of veterinary injectables, specifically to a tylosin ketoprofen injection and its preparation method. Background technology:

[0002] Respiratory infections are among the most difficult infectious diseases to control in animal husbandry, posing a serious threat to livestock production. Epidemics of respiratory infections can cause enormous economic losses to livestock operations. Therefore, how to prevent and control respiratory infections in pigs, cattle, and other livestock is an important research topic for veterinarians and veterinary drug practitioners. Because respiratory infections are generally multiple infections with numerous pathogenic factors and complex symptoms, there are currently no highly effective preventative measures. For animal respiratory infections, while seeking biological control and environmental intervention, drug treatment remains the primary approach. Developing novel antibacterial drugs that are effective, safe, broad-spectrum, highly effective, and have low residues for respiratory infections is an important direction in veterinary drug research and development.

[0003] Tylamycin is a semi-synthetic macrolide antibiotic. Macrolide antibiotics inhibit the biosynthesis of essential proteins by selectively binding to bacterial ribosomal RNA. They act by promoting the dissociation of polypeptide-tRNA from the ribosome during translocation. Unlike many other macrolide antibiotics, it has a longer duration of action, partly due to the presence of three amino groups in its structure. Tylamycin is effective in vitro against *Pasteurella multocida*, *Pasteurella multocida*, *Haemophilus hygroscopicus*, and *Mycoplasma bovis*, as well as *Actinobacillus pleuropneumoniae*, *Pasteurella multocida*, and *Mycoplasma pneumoniae*. A readily soluble, safe, and highly effective water-soluble tylamycin-ketoprofen injection was prepared by combining tylamycin with ketoprofen and using polyamide dendritic molecules as a solubilizer.

[0004] Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) that provides antipyretic and analgesic effects. It belongs to the aromatic propionic acid derivatives family and possesses anti-inflammatory, analgesic, and antipyretic properties. Its main mechanism of action involves interfering with cyclooxygenase in the arachidonic acid metabolic pathway, thereby reducing the production of inflammatory mediators such as prostaglandins and thromboxanes, thus exerting its anti-inflammatory, analgesic, and antipyretic effects.

[0005] When used in combination with tylosin, it not only kills bacteria but also reduces inflammation, achieving a dual synergistic effect. Currently, there are also drugs available on the market that combine tylosin with tylosin, such as commercially available tylosin-ketoprofen injection. However, commercially available tylosin-ketoprofen injection has a slower onset of action, and while clinical signs may improve, relapses are common. Summary of the Invention:

[0006] To address the aforementioned problems and overcome the shortcomings of existing technologies, this invention provides a tylosin ketoprofen injection and its preparation method, which can effectively solve the problems of slow efficacy and recurrence of clinical signs in commercially available tylosin ketoprofen injections.

[0007] The specific technical solution of the present invention to solve the above-mentioned technical problems is as follows: a tylosin-ketoprofen injection, characterized in that: the formulation components include: tylosin, ketoprofen, catalyst, antioxidant and injection solvent.

[0008] Furthermore, the mass ratio of tylosin to ketoprofen is (1–1.2):(1–1.2).

[0009] Furthermore, the formula contains the following components per 100 ml:

[0010]

[0011] The pH of the tylosin ketoprofen injection is 5.5–6.5.

[0012] Furthermore, the catalytic factor is a polyamide amine dendritic molecule.

[0013] Furthermore, the antioxidant is one or a mixture of two or more of thioglycerol, sodium metabisulfite, or sodium bisulfite.

[0014] Furthermore, the solvent for injection is water for injection.

[0015] A method for preparing tylosin ketoprofen injection, the method comprising the following steps:

[0016] Step 1: Weigh 90% of the prescribed amount of water for injection, add the catalyst, and stir until completely dissolved;

[0017] Step 2: Add the required amount of ketoprofen from the formula and stir until completely dissolved;

[0018] Step 3: Add the required amount of tylosin according to the formula and stir until completely dissolved;

[0019] Step 4: Add the antioxidant according to the formula components and stir to disperse evenly;

[0020] Step 5: Add the remaining water for injection and check the pH of the solution to be 5.5–6.5.

[0021] This yields tylosin ketoprofen injection.

[0022] The beneficial effects of this invention are:

[0023] (1) Since tylosin raw material is poorly soluble in water, in this invention, tylosin is used in combination with ketoprofen. After adding polyamide dendritic molecules, there is no need to use pH adjuster. The combination of the two results in an aqueous injection solution that has a fast onset of action, rapid absorption after administration, and short duration of action. It can play a synergistic role in sterilization and anti-inflammation, which can not only increase the efficacy of a single drug, but also improve drug stability and increase bioavailability.

[0024] (2) In this invention, tylosin and ketoprofen are both insoluble in water. Polyamide dendritic molecules act as catalysts and can dissolve tylosin and ketoprofen. In addition, polyamide dendritic molecules have a spherical structure and a large specific surface area, which can accelerate the release of tylosin and ketoprofen and achieve rapid onset of action.

[0025] (3) In this invention, both tylosin and ketoprofen are insoluble in water. In the prior art, both encapsulation and heating techniques are used to achieve the solubilization effect. This invention utilizes the structural characteristics of polyamide amine dendritic molecules to solubilize the drug. The dissolution process does not require heating and the amount used is small, which avoids drug decomposition. The antioxidant is added last and the preparation process does not require nitrogen protection. Polyamide amine dendritic molecules can protect the drug from slow release and increase its stability.

[0026] (4) The present invention is an aqueous solution and does not require the addition of organic solvents such as ethanol and propylene glycol to aid dissolution, which reduces irritation and greatly increases its safety. Attached image description:

[0027] Appendix Figure 1 This is a chromatogram of the total impurity content prepared according to Example 1 of the present invention;

[0028] Appendix Figure 2 This is a chromatogram of total impurities after one week of low-temperature treatment according to Example 1 of the present invention;

[0029] Appendix Figure 3 This is the chromatogram of total impurities in Comparative Example 4 of this invention;

[0030] Appendix Figure 4 This is the chromatogram of total impurity content in Comparative Example 4 of the present invention after one week of low-temperature treatment;

[0031] Appendix Figure 5 This is the chromatogram of total impurities in Comparative Example 5 of this invention;

[0032] Appendix Figure 6 This is the chromatogram of total impurities in Comparative Example 5 of the present invention after one week of low-temperature treatment;

[0033] Appendix Figure 7 This is the chromatogram of total impurities in Comparative Example 6 of this invention;

[0034] Appendix Figure 8 This is the chromatogram of total impurities in Comparative Example 6 of the present invention after one week of low-temperature treatment;

[0035] Appendix Figure 9 This is a diagram of the current assembly state of Comparative Example 6 of the present invention;

[0036] Appendix Figure 10 This is a diagram of the current assembly state of Comparative Example 4 of the present invention;

[0037] Appendix Figure 11 This is a diagram showing the state of the low-temperature treatment for one week in Comparative Example 4 of this invention;

[0038] Appendix Figure 12 This is a diagram showing the current configuration state of Embodiment 1 of the present invention;

[0039] Appendix Figure 13 This is a diagram showing the state of the low-temperature treatment for one week in Embodiment 1 of the present invention; Detailed implementation method:

[0040] Specific details in the description of this invention are merely to provide a thorough understanding of the embodiments thereof; however, those skilled in the art should understand that the implementation of this invention is not limited to these details. Furthermore, well-known structures and functions have not been described or shown in detail to avoid obscuring the key points of the embodiments of this invention. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0041] Specific embodiments of the present invention:

[0042] To better understand the present invention, specific embodiments are described. It is worth emphasizing that the effects of these embodiments are not substantially different from those of various embodiments within the scope of protection of the present invention, including the materials and their content ratios. All of them can achieve the effects described in the present invention and solve the above-mentioned problems. Other combinations will not be described here.

[0043] Example 1: Typrinycin-Ketoprofen Injection

[0044]

[0045] Specific preparation method:

[0046] Step 1: Weigh 90% of the prescribed amount of water for injection, add polyamide amine dendritic molecules, and stir until completely dissolved;

[0047] Step 2: Add the required amount of ketoprofen from the formula and stir until completely dissolved;

[0048] Step 3: Add the required amount of tylosin according to the formula and stir until completely dissolved;

[0049] Step 4: Add the required amount of thioglycerol from the formula and stir to disperse evenly;

[0050] Step 5: Add the remaining water for injection and check the pH of the solution to be 5.5–6.5.

[0051] This yields tylosin ketoprofen injection.

[0052] Example 2: Typrinycin-Ketoprofen Injection

[0053]

[0054] Specific preparation method:

[0055] Step 1: Weigh 90% of the prescribed amount of water for injection, add polyamide amine dendritic molecules, and stir until completely dissolved;

[0056] Step 2: Add the required amount of ketoprofen from the formula and stir until completely dissolved;

[0057] Step 3: Add the required amount of tylosin according to the formula and stir until completely dissolved;

[0058] Step 4: Add the required amount of thioglycerol from the formula and stir to disperse evenly;

[0059] Step 5: Add the remaining water for injection and check the pH of the solution to be 5.5–6.5.

[0060] This yields tylosin ketoprofen injection.

[0061] Example 3: Typrinycin-Ketoprofen Injection

[0062]

[0063] Specific preparation method:

[0064] Step 1: Weigh 90% of the prescribed amount of water for injection, add polyamide amine dendritic molecules, and stir until completely dissolved;

[0065] Step 2: Add the required amount of ketoprofen from the formula and stir until completely dissolved;

[0066] Step 3: Add the required amount of tylosin according to the formula and stir until completely dissolved;

[0067] Step 4: Add the required amount of thioglycerol from the formula and stir to disperse evenly;

[0068] Step 5: Add the remaining water for injection and check the pH of the solution to be 5.5–6.5.

[0069] This yields tylosin ketoprofen injection.

[0070] To more intuitively demonstrate the technological advantages of this invention, a comparison is made between the tylosin-ketoprofen injection and preparation method used in this invention, and a method employing equivalent substitutions in the same process.

[0071] Comparative Example 1:

[0072] The preparation method is the same as in Example 1, except that no catalyst, polyamide amine dendritic molecule, was added during the preparation of this comparative example.

[0073] Comparative Example 2:

[0074] The preparation method is the same as in Example 1, except that the catalyst is replaced with 2-pyrrolidone in the preparation process of this comparative example.

[0075] Comparative Example 3:

[0076] The preparation method is the same as in Example 1, except that the catalyst is replaced with Tween-80 in the preparation process of this comparative example.

[0077] Comparative Example 4:

[0078] The preparation method is the same as in Example 1, except that the catalyst is replaced with 2-pyrrolidone in the preparation process of this comparative example.

[0079] In terms of preparation method: In the second step, add the prescribed amount of ketoprofen, heat to 65°C, and stir until completely dissolved;

[0080] Comparative Example 5:

[0081] The preparation method is the same as in Example 1, except that the catalyst is replaced with Tween-80 in the preparation process of this comparative example.

[0082] In terms of preparation method: In the second step, add the prescribed amount of ketoprofen, heat to 65°C, and stir until completely dissolved;

[0083] Comparative Example 6:

[0084] The preparation method is the same as in Example 1, except that in the second step of the preparation process of this comparative example, the prescribed amount of ketoprofen is added, heated to 65°C, and stirred until completely dissolved.

[0085] Comparative Example 7:

[0086] The preparation method is the same as that of Comparative Example 1, except that no catalyst was added during the preparation of this comparative example. In the second step, the prescribed amount of ketoprofen was added, heated to 65°C, and stirred until completely dissolved.

[0087] Table 1: Comparison of Day 0 Results between Different Comparative Examples and the Invention

[0088] sample Catalyst Total impurities (%) Dissolved state Dissolution time Heating required Example 1 Polyamidoamine dendritic molecules 0.47 Dissolve 20 minutes no Comparative Example 1 - - Insoluble matter - no Comparative Example 2 2-Pyrrolidone Insoluble matter - no Comparative Example 3 Twain-80 Insoluble matter - no Comparative Example 4 2-Pyrrolidone 3.7 Dissolve 1 hour Heat to 65℃ Comparative Example 5 Twain-80 5.3 Dissolve 1.5 hours Heat to 65℃ Comparative Example 6 Polyamidoamine dendritic molecules 4.9 Dissolve 20 minutes Heat to 65℃ Comparative Example 7 - - Insoluble matter - Heat to 65℃ limit - 5.0 - - -

[0089] Analysis of the data in Table 1 shows that:

[0090] (1) Compared with Example 1, Comparative Examples 1-3 all showed the phenomenon of non-dissolution, which does not meet the requirements of the National Pharmacopoeia for injections.

[0091] This may be due to the electrostatic attraction between the carboxyl groups at the ends of the polyamide dendritic molecule and the amino groups in the tylosin structure, and the electrostatic attraction between the amino groups at the ends of the polyamide dendritic molecule and the carboxyl groups in the ketoprofen structure, which allows tylosin and ketoprofen to quickly enter their molecular interior, thereby achieving a catalytic effect. This allows tylosin and ketoprofen to dissolve. Furthermore, the polyamide dendritic molecule has a spherical structure with a large specific surface area, which can accelerate the release of tylosin and ketoprofen, achieving a rapid onset of action.

[0092] (2) Compared with Comparative Example 2-3, Comparative Example 4-5 added a catalyst: Tween-80 or 2-pyrrolidone and underwent heating treatment. No insolubility problem occurred. Therefore, the dissolution was due to heating. This is also the standard practice for commercially available tylosin-ketoprofen injections. It can effectively solve the problem of insolubility when tylosin and ketoprofen are used together. However, heating leads to unstable product quality. See Table 2 for details.

[0093] (3) Compared with Comparative Example 1, Comparative Example 7 did not add a catalyst and only underwent heating treatment. It was able to dissolve some of the reagents, but still did not completely dissolve them, which does not meet the requirements of the National Pharmacopoeia for injections.

[0094] Therefore, this invention creatively discovers that the catalytic factor—polyamide dendritic molecule—can effectively solubilize tylosin and ketoprofen at room temperature with low total impurity content. In contrast, conventional cosolvents such as 2-pyrrolidone and Tween-80 have high total impurity content, require heating during the process, have long dissolution times, and pose a risk of drug decomposition.

[0095] Table 2: Performance Comparison of Different Comparative Examples and the Invention after One Week of Low-Temperature Placement Test

[0096]

[0097] Among them, the results of low-temperature storage for 1 week showed that all samples prepared in Comparative Examples 4-5 precipitated insoluble matter after low-temperature storage, and the total impurity content increased significantly. Furthermore, the sample prepared in Comparative Example 6 was a clear yellow liquid on day 0, unlike the colorless clear liquid of other similar products; its color deepened especially after low-temperature storage. In contrast, the sample quality of Example 1 showed no significant change after low-temperature storage. (See details...) Figure 9-13 ;

[0098] Analysis of the data in Table 2 shows that:

[0099] (1) As can be seen from the comparison between Example 1 and Comparative Examples 4-5:

[0100] Although Comparative Examples 4-5, even with the addition of catalysts such as Tween-80 or 2-pyrrolidone, still required heating to obtain an injection solution with solubility conforming to the national pharmacopoeia, heating involves a long dissolution time and carries the risk of drug decomposition.

[0101] The results of the low-temperature storage test showed that the samples prepared by heating tylosin and ketoprofen had poor stability after storage, which verified the above statement.

[0102] To more intuitively demonstrate the technological advantages of this invention, a comparison is made between the tylosin-ketoprofen injection prepared using the method of this invention and a method using equivalent substitution with the same process.

[0103] Comparative Example 8:

[0104] Tylenol injection

[0105]

[0106] Specific preparation method:

[0107] Step 1: Weigh 90% of the prescribed amount of water for injection, add polyamide amine dendritic molecules, and stir until completely dissolved;

[0108] Step 2: Add the prescribed amount of tylosin;

[0109] Step 3: Add an appropriate amount of hydrochloric acid to adjust the pH to 5.5-6.5, and stir until tylosin is completely dissolved;

[0110] Step 4: Add the prescribed amount of thioglycerin and stir to disperse evenly;

[0111] Step 5: Add the remaining water for injection and check the pH of the solution to be 5.5–6.5.

[0112] This yields tylosin ketoprofen injection.

[0113] Comparative Example 9:

[0114] Tylenol injection

[0115]

[0116]

[0117] Specific preparation method:

[0118] Step 1: Weigh 90% of the prescribed amount of water for injection, add polyamide amine dendritic molecules, and stir until completely dissolved;

[0119] Step 2: Add the prescribed amount of tylosin;

[0120] Step 3: Add an appropriate amount of citric acid to adjust the pH to 5.5-6.5, and stir until tylosin is completely dissolved;

[0121] Step 4: Add the prescribed amount of thioglycerin and stir to disperse evenly;

[0122] Step 5: Add the remaining water for injection and check the pH of the solution to be 5.5–6.5.

[0123] This yields tylosin ketoprofen injection.

[0124] The content of tylosin-ketoprofen injection prepared in Example 1 and tylosin injection prepared in Comparative Examples 8 and 9 were determined, and related substances were detected and solubility was recorded. The results are shown in the table below:

[0125] Table 3: Comparison of experimental results between different comparative examples and the present invention

[0126] sample Dissolved state Tylosin content (%) Total impurities (%) Example 1 Completely dissolved 98.7 0.47 Comparative Example 8 Insoluble matter - - Comparative Example 9 Completely dissolved 89.2 4.7 limit - 90-110 5.0

[0127] Analysis of the test results of Comparative Examples 8 and 9 shows that when the pH was adjusted using conventional pH adjusters, the tylosin content did not reach the normal limit and the total impurity content was high. However, the use of ketoprofen not only adjusted the pH of the solution, but also had a better binding with polyamide dendritic molecules, resulting in a better solubilizing effect.

[0128] To more intuitively demonstrate the process advantages of this invention, accelerated and long-term tests were conducted on the tylosin-ketoprofen injection solution prepared according to this invention. The tylosin-ketoprofen injection solution was prepared using either proportional scaling-up or multiple sampling preparations, with no difference between the two methods. The results of the accelerated and long-term tests are as follows.

[0129] The samples prepared in Example 1 were subjected to accelerated testing (40±2℃, RH 75%±5%) and long-term testing (25±2℃, RH 60%±5%) to examine their stability. Samples were also taken to test the content, related substances, pH value, and other quality indicators. The test results are shown in Tables 4 and 5 below:

[0130] Table 4: Accelerated Test Results of the Tylamycin-Ketoprofen Injection Solution of the Present Invention

[0131]

[0132] Table 5: Long-term test results of the tylosin ketoprofen injection of the present invention

[0133]

[0134] The results of accelerated and long-term tests (Tables 4 and 5) show that the tyromycin-ketoprofen injection of the present invention did not show significant changes in appearance or pH value after being placed under accelerated conditions (40±2℃, RH 75%±5%) for 6 months and under long-term conditions (25±2℃, RH 60%±5%) for 24 months. All quality indicators, including the content of tyromycin and ketoprofen and related substances, were qualified, indicating that the tyromycin-ketoprofen injection of the present invention has good quality stability.

[0135] To more intuitively demonstrate the process advantages of this invention, a parallel comparison is made between the tylosin-ketoprofen injection prepared according to this invention and commercially available tylosin injection, commercially available ketoprofen injection, and commercially available tylosin-ketoprofen injection.

[0136] Sixty beef cattle diagnosed with Pasteurella infection were treated and divided into four groups. They were injected with tylosin-ketoprofen injection, commercially available tylosin injection, commercially available ketoprofen injection, and commercially available tylosin-ketoprofen injection, respectively. Clinical symptoms were observed and recorded before each administration, and the observation period was 7 days.

[0137] The test materials included:

[0138] Test drug: Tylenol ketoprofen injection prepared in Example 1, administered subcutaneously once daily for 3 consecutive days, at a dose of 0.025 ml / kg.

[0139] Control drug 1: Commercially available tylosin injection, administered subcutaneously once daily for 3 consecutive days, at a dose of 0.025 ml / kg.

[0140] Control drug 2: Commercially available ketoprofen injection, subcutaneous injection, once daily for 3 consecutive days, at a dose of 0.03 ml / kg.

[0141] Control drug 3: Commercially available tylosin ketoprofen injection, administered subcutaneously once daily for 3 consecutive days, at a dose of 0.025 ml / kg.

[0142] (1) Body temperature changes: Rectal temperature was measured at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, and 72 hours after drug administration. The average value of each group was recorded. The results are shown in Table 6.

[0143] Table 6: Body Temperature Changes in In Vivo Experiments of the Tylamycin-Ketoprofen Injection Solution of the Present Invention

[0144]

[0145] Conclusion: After administration of the sample prepared in Example 1, the body temperature of the sick cattle rapidly dropped to normal within two hours and did not rise again. However, after administration of tylosin injection alone and ketoprofen injection alone, the body temperature dropped more slowly and was more prone to relapse. The commercially available tylosin-ketoprofen injection also showed a slower temperature drop after administration. This indicates that the tylosin-ketoprofen injection of the present invention is rapidly absorbed, has a fast onset of action, and a long duration of action.

[0146] (2) Weight change: Weight changes were recorded within 7 days after administration, and the average value was measured. The results are shown in Table 7.

[0147] Table 7: Body weight gain in in vivo experiments of the tylosin-ketoprofen injection of the present invention

[0148] 1 2 3 4 5 6 7 Example 1 0.28 0.80 0.94 1.05 1.28 1.42 1.78 Reference Standard 1 0.02 0.05 -0.05 -0.15 -0.87 -1.02 -1.07 Reference Standard 2 0.05 0.06 0.01 -0.12 -0.18 -0.29 -0.55 Reference Standard 3 0.10 0.20 0.26 0.41 0.37 0.34 0.43

[0149] Conclusion: After administration of the sample prepared in Example 1, the weight of the diseased cattle gradually increased. However, after administration of tylosin injection alone or ketoprofen injection alone, there was no significant increase in weight. Although the weight of the diseased cattle increased after administration of commercially available tylosin-ketoprofen injection, the increase was slow. This indicates that the tylosin-ketoprofen injection of the present invention is rapidly absorbed and has a significant therapeutic effect.

[0150] (3) Changes in clinical signs: Clinical symptoms of cattle were monitored and recorded daily for 7 days after administration. Based on feeding status, mental state, feces, coughing, and the degree of nasal mucus discharge, the symptoms were graded into four levels according to severity: 0 - normal, 1 - mild, 2 - moderate, 3 - severe. Results are shown in Tables 8 and 9.

[0151] Table 8: Clinical Symptom Scoring Criteria for the In Vivo Treatment of the Tylamycin-Ketoprofen Injection of the Present Invention

[0152]

[0153] Table 9: Changes in in vivo clinical signs of the teratin ketoprofen injection of the present invention

[0154] 1 2 3 4 5 6 7 Example 1 2.8 2.0 1.2 0.3 0 0 0 Reference Standard 1 2.7 2.6 2.1 1.6 2.1 1.2 0.9 Reference Standard 2 2.9 2.8 2.7 2.1 2.1 2.0 1.9 Reference Standard 3 2.8 2.3 1.8 1.5 0.9 1.2 1.5

[0155] The data above show that after administering the sample prepared in Example 1, the clinical signs of the sick cattle improved significantly and eventually returned to normal. However, after administering tylosin injection alone or ketoprofen injection alone, there was no significant improvement in clinical signs. After administering commercially available tylosin-ketoprofen injection, the clinical signs of the sick cattle improved but were prone to relapse. This indicates that the tylosin-ketoprofen injection of the present invention is rapidly absorbed after administration, increases the efficacy of single-drug use, has a synergistic bactericidal and anti-inflammatory effect, and has good clinical compliance and scalability.

[0156] In summary: (1) Since tylosin is poorly soluble in water, the combination of tylosin and ketoprofen in this invention eliminates the need for pH adjusters after the addition of polyamide dendritic molecules. Furthermore, the combined use of the two drugs results in rapid onset of action, rapid absorption after administration, and a short duration of action, providing a synergistic effect of bactericidal and anti-inflammatory action. This not only enhances the efficacy of single drugs but also improves drug stability and bioavailability.

[0157] (2) In this invention, tylosin and ketoprofen are both insoluble in water, while polyamide dendritic molecules are readily soluble in water. Polyamide dendritic molecules are used as catalysts. The electrostatic attraction between the carboxyl group at the end of the polyamide dendritic molecule and the amino group in the structure of tylosin is utilized. Furthermore, the electrostatic attraction between the amino group at the end of the polyamide dendritic molecule and the carboxyl group in the structure of ketoprofen is utilized. This allows tylosin and ketoprofen to quickly enter their molecular interior, thereby achieving the catalytic effect. It can also dissolve tylosin and ketoprofen. Moreover, the polyamide dendritic molecule has a spherical structure and a large specific surface area, which can accelerate the release of tylosin and ketoprofen, achieving a rapid onset of action.

[0158] (3) In this invention, both tylosin and ketoprofen are insoluble in water. In the prior art, both encapsulation and heating techniques are used to achieve the solubilization effect. This invention utilizes the structural characteristics of polyamide amine dendritic molecules to solubilize the drug. The dissolution process does not require heating and the amount used is small, which avoids drug decomposition. The antioxidant is added last and the preparation process does not require nitrogen protection. Polyamide amine dendritic molecules can protect the drug from slow release and increase its stability.

[0159] (4) The present invention is an aqueous solution and does not require the addition of organic solvents such as ethanol and propylene glycol to aid dissolution, which reduces irritation and greatly increases its safety.

Claims

1. A telithromycin ketoprofen injection solution, characterized in that: The formula components include: telithromycin, ketoprofen, catalytic agent, antioxidant and water for injection, and the catalytic agent is a spherical polyamide amine dendrimer; The preparation method of the telithromycin ketoprofen injection includes the following steps: Step one: weigh 90% of the prescription amount of water for injection, add the catalytic agent, and stir to dissolve completely; Step two: add the formula component amount of ketoprofen, and stir to dissolve completely; Step three: add the formula component amount of telithromycin, and stir to dissolve completely; Step four: add the formula component amount of antioxidant, and stir to disperse uniformly; Step five: add the remaining amount of water for injection, detect the pH of the solution to be 5.5-6.5, and the telithromycin ketoprofen injection is prepared.

2. The telavancin ketoprofen injection of claim 1, wherein: The mass ratio of telithromycin and ketoprofen is (1-1.2):(1-1.2).

3. The telavancin ketoprofen injection solution according to claim 1 or 2, characterized in that: The formula components in 100ml include: Telithromycin 10-12g; Ketoprofen 10-12g; Catalytic agent 1-5g; Antioxidant 0.4-0.6g; Water for injection to 100ml, The pH of the telithromycin ketoprofen injection is 5.5-6.

5.

4. The telavancin ketoprofen injection of claim 3, wherein: The antioxidant is one or a mixture of two or more of thio-glycerol, sodium metabisulfite or sodium bisulfite.

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