Veterinary carprofen injection and preparation method thereof

Abstract

The invention relates to the technical field of veterinary drugs, and particularly provides a veterinary carprofen injection and a preparation method thereof, the veterinary carprofen injection comprises carprofen, emodin, galuteolin, coumarin, Radix Astragali, wolfberry, Schisandra chinensis, resveratrol and other components. According to the veterinary carprofen injection, emodin and luteoloside are added for compound anti-inflammation, the dosage of carprofen is reduced, the kidney burden is relieved, meanwhile, drug resistance is not likely to be generated, radix astragali, fructus lycii and fructus schizandrae extracts are added for protecting the kidney, regulating immunity and avoiding renal function damage, and finally the effects of compound anti-inflammation and renal function damage avoiding are achieved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of veterinary medicine, in particular to a veterinary carprofen injection and a preparation method thereof. BACKGROUND

[0002] Carprofen has the effects of antipyretic, analgesic and anti-inflammatory, and can reduce the clinical symptoms of acute infectious respiratory disease and acute mastitis in cattle, such as fever; as a non-steroidal anti-inflammatory drug, carprofen injection plays an important role in the field of analgesia and anti-inflammation in veterinary medicine, and in the pharmacokinetics, carprofen injection shows good bioavailability and a long elimination half-life; in the bovine body, after subcutaneous injection of carprofen injection, absorption is rapid, elimination is slow, and bioavailability is high. These characteristics make carprofen injection particularly suitable for clinical situations requiring long-acting analgesia and anti-inflammation in cattle and other animals.

[0003] However, the required dose of carprofen for long-term single use of anti-inflammatory is large, and is prone to drug resistance, and also has a large burden on kidney function, therefore, a compound anti-inflammatory veterinary carprofen injection and a preparation method thereof are needed to avoid damage to kidney function. SUMMARY

[0004] In order to solve the above problems, the purpose of the present application is to provide a veterinary carprofen injection and a preparation method thereof.

[0005] In one aspect, the present application provides a preparation method of a veterinary carprofen injection, which comprises the following steps: Take carprofen with a mass fraction of 3-7%, emodin with a mass fraction of 2-4%, luteoloside with a mass fraction of 1.5-3%, coumarin with a mass fraction of 0.3-0.5%, astragalus with a mass fraction of 4.5-7.5%, medlar with a mass fraction of 3-5%, schisandra chinensis with a mass fraction of 2-4%, resveratrol with a mass fraction of 0.3-0.5%, ethanol with a mass fraction of 10-12%, glycine with a mass fraction of 0.4-0.6%, and 0.9% physiological saline to make up the rest as a material to be used; The astragalus, the medlar and the schisandra chinensis are chopped and passed through a 20-mesh sieve, 80% ethanol with a mass 10 times that of the astragalus, the medlar and the schisandra chinensis is added at 20℃ for 5h, a flash extractor is added, and after extraction at a speed of 2000r / min for 50s, a 1200-mesh filter is used to obtain an extract; after adding 0.2 times the mass of the extract to the extract, vacuum distillation is carried out at 73℃ under a vacuum degree of 850mbar until no liquid continuously flows out, the remaining liquid is collected, and the material to be used except the astragalus, the medlar and the schisandra chinensis is added and stirred uniformly, and then filtered through a 0.22μm pore size to obtain the veterinary carprofen injection.

[0006] Further, the mass fraction of the carprofen is 5%.

[0007] Further, the mass fraction of the emodin is 3%.

[0008] Further, the mass fraction of the syringin is 2.2%.

[0009] Further, the mass fraction of the coumarin is 0.4%.

[0010] Further, the mass fraction of the astragalus is 6%.

[0011] Further, the mass fraction of the medlar is 4%.

[0012] Further, the mass fraction of the schisandra is 3%.

[0013] Further, the mass fraction of the resveratrol is 0.4%.

[0014] Further, the mass fraction of the ethanol is 11%.

[0015] Further, the mass fraction of the glycine is 0.5%.

[0016] In another aspect, the present application provides a veterinary carprofen injection prepared by the preparation method of the veterinary carprofen injection as described above.

[0017] The present application can bring the following beneficial effects: The veterinary carprofen injection of the present application has the following advantages: first, the addition of emodin and syringin can reduce the dosage of carprofen, reduce the burden on the kidney, and is not easy to produce drug resistance; second, the addition of coumarin can promote blood circulation and improve the absorption efficiency of the drug; third, the addition of astragalus, medlar and schisandra extract can protect the kidney, regulate immunity and avoid kidney function damage; fourth, the addition of resveratrol can stabilize the drug system; in addition, the addition of ethanol and glycine can improve the stability of the drug; finally, the effect of compound anti-inflammatory and avoiding kidney function damage is achieved.

[0018] The vacuum distillation temperature of this invention removes ethanol as much as possible while minimizing the volatilization and loss of components such as Astragalus membranaceus, Lycium barbarum, and Schisandra chinensis. The ethanol immersion process of this invention considers the difficulty of immersing the medicinal materials and the fragmentation efficiency of subsequent flash extraction, ensuring sufficient immersion of the medicinal materials to improve the flash extraction effect while preventing the loss and deterioration of active substances. Under the unique process and proportions of this invention, the above-mentioned components collectively achieve the compound anti-inflammatory effect of this invention while avoiding renal damage, including synergistic drug efficacy and coordinated system stability. It should be noted that the process parameters and drug proportions of this invention cannot be obtained through simple experiments and have a certain degree of randomness and inventiveness. The proportions of each component should not only consider their individual efficacy but also their impact on overall stability. Detailed Implementation

[0019] To more clearly illustrate the overall concept of the present invention, the overall solution of the present invention will be described in detail below by way of embodiments; in the following description, numerous specific details are set forth in order to provide a more thorough understanding of the present invention; however, it will be apparent to those skilled in the art that the present invention may be practiced without one or more of these details; in other instances, some technical features known in the art have not been described in order to avoid confusion with the present invention.

[0020] In this invention, carbofen (CAS number 53716-49-7), emodin (CAS number 518-82-1), luteolin (CAS number 5373-11-5), coumarin (CAS number 91-64-5), resveratrol (CAS number 501-36-0), glycine (CAS number 56-40-6), astragalus, wolfberry, and schisandra were purchased from Bozhou Jincaotang Biotechnology Co., Ltd., and were found to contain 2.17% astragalus polysaccharide, 4.58% wolfberry polysaccharide, and 1.33% schisandra acid.

[0021] Unless otherwise specified, all raw material components in the following examples are commercially available, all experimental instruments used are standard laboratory instruments, and the performance testing methods are those known in the art. The overall ambient temperature was 25°C and the air humidity was 30%.

[0022] The preferred implementation method is as follows: Example 1: The following method was used to prepare veterinary carbofen injection: Take 5% carbofenone, 3% emodin, 2.2% luteolin, 0.4% coumarin, 6% astragalus, 4% wolfberry, 3% schisandra, 0.4% resveratrol, 11% ethanol, 0.5% glycine, and 0.9% physiological saline to make up the remaining weight as raw materials; The Astragalus membranaceus, Lycium barbarum, and Schisandra chinensis were chopped and passed through a 20-mesh sieve. They were then immersed in 80% ethanol (10 times the mass of the Astragalus membranaceus, Lycium barbarum, and Schisandra chinensis) at 20°C for 5 hours. A flash extractor was then used, and the mixture was extracted for 50 seconds at 2000 rpm. The extract was then filtered through a 1200-mesh sieve to obtain the extract. 0.2 times the mass of the extract was added to the extract, and the mixture was then distilled under reduced pressure at 73°C and 850 mbar until no liquid flowed continuously. The remaining liquid was collected, and the remaining ingredients (excluding the Astragalus membranaceus, Lycium barbarum, and Schisandra chinensis) were added and stirred until homogeneous. The mixture was then filtered through a 0.22 μm pore size filter to obtain the veterinary carboprofen injection solution.

[0023] Examples 2-9: The only difference between Example 2 and Example 1 is that the mass fraction of carboprofen is 3%. The only difference between Example 3 and Example 1 is that the mass fraction of carboprofen is 7%. The only difference between Example 4 and Example 1 is that the mass fraction of emodin is 2%; The only difference between Example 5 and Example 1 is that the mass fraction of emodin is 4%; The only difference between Example 6 and Example 1 is that the mass fraction of luteolin is 1.5%; The only difference between Example 7 and Example 1 is that the mass fraction of luteolin is 3%; The only difference between Example 8 and Example 1 is that the mass fraction of Astragalus membranaceus is 4.5%. The only difference between Example 9 and Example 1 is that the mass fraction of Astragalus membranaceus is 7.5%.

[0024] Comparative Examples 1-27: The only difference between Comparative Example 1 and Example 1 is that the mass fraction of carboprofen is 1.5%; The only difference between Comparative Example 2 and Example 1 is that the mass fraction of carboprofen is 14%. The only difference between Comparative Example 3 and Example 1 is that the mass fraction of emodin is 1%; The only difference between Comparative Example 4 and Example 1 is that the mass fraction of emodin is 8%; The only difference between Comparative Example 5 and Example 1 is that the mass fraction of luteolin is 0.7%; The only difference between Comparative Example 6 and Example 1 is that the mass fraction of luteolin is 6%; The only difference between Comparative Example 7 and Example 1 is that the mass fraction of Astragalus membranaceus is 2%; The only difference between Comparative Example 8 and Example 1 is that the mass fraction of Astragalus membranaceus is 15%. The only difference between Comparative Example 9 and Example 1 is that the mass fraction of coumarin is 0.1%; The only difference between Comparative Example 10 and Example 1 is that the mass fraction of coumarin is 1%; The only difference between Comparative Example 11 and Example 1 is that the mass fraction of wolfberry is 1%; The only difference between Comparative Example 12 and Example 1 is that the mass fraction of wolfberry is 10%. The only difference between Comparative Example 13 and Example 1 is that the mass fraction of Schisandra chinensis is 1%; The only difference between Comparative Example 14 and Example 1 is that the mass fraction of Schisandra chinensis is 8%; The only difference between Comparative Example 15 and Example 1 is that the resveratrol mass fraction is 0.1%; The only difference between Comparative Example 16 and Example 1 is that the resveratrol mass fraction is 2%; The only difference between Comparative Example 17 and Example 1 is that the mass fraction of ethanol is 5%; The only difference between Comparative Example 18 and Example 1 is that the mass fraction of ethanol is 20%. The only difference between Comparative Example 19 and Example 1 is that the mass fraction of glycine is 0.2%; The only difference between Comparative Example 20 and Example 1 is that the mass fraction of glycine is 1.5%; The only difference between Comparative Example 21 and Example 1 is that the temperature of vacuum distillation is 85°C; The only difference between Comparative Example 22 and Example 1 is that emodin is replaced with luteolin in the same mass ratio as in Example 1. The only difference between Comparative Example 23 and Example 1 is that luteolin is replaced with emodin in the same mass ratio as in Example 1. The only difference between Comparative Example 24 and Example 1 is that Astragalus membranaceus was replaced with Lycium barbarum and Schisandra chinensis in the same mass ratio as in Example 1. The only difference between Comparative Example 25 and Example 1 is that the wolfberry was replaced with Astragalus membranaceus and Schisandra chinensis in the same mass ratio as in Example 1; The only difference between Comparative Example 26 and Example 1 is that Schisandra chinensis is replaced with Astragalus membranaceus and Lycium barbarum in the same mass ratio as in Example 1. The only difference between Comparative Example 27 and Example 1 is that the substitutes other than carbofen and ethanol were replaced with an equal mass of 0.9% saline.

[0025] Prepare three times the number of adult Holstein cows weighing 450±30 kg with inflammation, and ensure that the initial sampled values ​​of their white blood cell concentrations are all within 16.5±0.5×10⁻⁶. 9 The serum creatinine level was 140 ± 10 µmol / L, and the concentration was 9 × 10⁻⁶. 9 The upper limit of normal leukocyte concentration is defined as 1 / L, and the upper limit of normal serum creatinine concentration is defined as 150 µmol / L. Each example corresponds to three experimental cattle mentioned above, using the injection solution of the corresponding example of this invention, specifically a single subcutaneous injection of 13 mL once daily for 8 days. Afterwards, the leukocyte concentration of each cattle was measured in blood. The average value of the data from the three cattle in each example is taken, in units of 10-1. 9 The concentration of serum creatinine in each cow was measured after 30 days of continuous administration. The average value of the data from 3 cows in each example was taken, and the unit was µmol / L, with integers retained. The results of the above experiment are shown in Table 1.

[0026] Table 1: Test results of white blood cell and serum creatinine in the corresponding bovine samples:

[0027] As can be seen from the data in Table 1, compared with other examples, the veterinary carbofen injection and its preparation method of the embodiments of the present invention, especially Embodiment 1 of the present invention, have the lowest blood leukocyte concentration and serum creatinine concentration in the corresponding experimental cattle under the same dosage; that is, the veterinary carbofen injection obtained by the present invention, especially Embodiment 1 of the present invention, has the best compound anti-inflammatory effect and avoids renal function damage.

[0028] The above description is merely an embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principle of the present invention should be included within the scope of the claims of the present invention.

Claims

1. A method for preparing a veterinary injectable solution of carprofen, characterized in that, The preparation method of the veterinary carprofen injection liquid comprises the following steps: Take carprofen with a mass fraction of 3-7%, emodin with a mass fraction of 2-4%, luteoloside with a mass fraction of 1.5-3%, coumarin with a mass fraction of 0.3-0.5%, astragalus with a mass fraction of 4.5-7.5%, medlar with a mass fraction of 3-5%, schisandra chinensis with a mass fraction of 2-4%, resveratrol with a mass fraction of 0.3-0.5%, ethanol with a mass fraction of 10-12%, glycine with a mass fraction of 0.4-0.6%, and 0.9% physiological saline to make up the rest as the to-be-used materials; The astragalus, the medlar and the schisandra chinensis are chopped and passed through a 20-mesh sieve, 80% ethanol with a mass 10 times that of the astragalus, the medlar and the schisandra chinensis is added to immerse for 5 h at 20°C, a flash extractor is added, and the extraction is carried out at a rotation speed of 2000 r / min for 50 s, then 1200-mesh filtration is carried out to obtain an extraction liquid; after the extraction liquid is supplemented with pure water with a mass of 0.2 times that of the extraction liquid, vacuum distillation is carried out at 73°C and a vacuum degree of 850 mbar until no liquid continuously flows out, the remaining liquid is collected, and the to-be-used materials except the astragalus, the medlar and the schisandra chinensis are added and stirred uniformly, then 0.22-μm pore size filtration is carried out to obtain the veterinary carprofen injection liquid.

2. The method of claim 1, wherein the carprofen injectable solution for veterinary use is prepared by, The mass fraction of the carprofen is 5%.

3. The method for preparing veterinary carbofen injection according to claim 1, characterized in that, The mass fraction of the emodin is 3%.

4. The method for preparing veterinary carbofen injection according to claim 1, characterized in that, The mass fraction of the luteoloside is 2.2%.

5. The method of claim 1, wherein the carprofen injectable solution for veterinary use is prepared by the steps of: The mass fraction of the coumarin is 0.4%.

6. The method of claim 1, wherein the carprofen injectable solution for veterinary use is prepared by the steps of: The mass fraction of the astragalus is 6%.

7. The method of claim 1, wherein the carprofen injectable solution for veterinary use is prepared by the steps of: The mass fraction of the medlar is 4%.

8. The method of claim 1, wherein the carprofen injectable solution for veterinary use is prepared by, The mass fraction of the schisandra chinensis is 3%.

9. The method of claim 1, wherein the veterinary carprofen injection is prepared by, The mass fraction of the resveratrol is 0.4%.

10. The method of claim 1, wherein the carprofen injectable solution for veterinary use is prepared by, The mass fraction of the ethanol is 11%.

11. The method of claim 1, wherein the veterinary carprofen injection is prepared by the steps of: The mass fraction of the glycine is 0.5%.

12. A veterinary carprofen injection liquid prepared by the preparation method of the veterinary carprofen injection liquid according to any one of claims 1-11.

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