Veterinary menbutone powder and preparation method thereof

[0012] Example 1. Study on the preparation process of veterinary membrone powder

[0013] Prescription: 300g of Mengbutone, 2700g of starch (or dry starch).

[0014] Preparation process I (direct mixing process): Weigh membrone and starch according to the prescription, mix for 20 minutes, pass through a No. 5 sieve, and get ready.

[0015] Preparation process II (mixing process after pretreatment of auxiliary materials): Dry the starch at 80±2°C for 4 hours to make the water content ≤6.0% to obtain dry starch, which is ready for use; weigh the membrone and dry starch according to the prescription and mix for 20 minutes , Go through the No. 5 sieve and get it.

[0016] Preparation process III (gradual mixing process after pretreatment of auxiliary materials): Dry the starch at 80±2°C for 4 hours to make the water content ≤6.0% to obtain dry starch, which is used as a reserve; Mumbutone is mixed with 1/3 of the prescription amount of dry starch for 5 minutes, then 1/3 of the prescription amount of dry starch is added, and mixed for 5 minutes, and then 1/3 of the prescription amount of dry starch is added, and mixed for 20 minutes. Sieve, that is.

[0017] Preparation process IV (gradual mixing and crushing process after pretreatment of auxiliary materials): Dry the starch at 80±2°C for 4 hours to make the water content ≤6.0% to obtain the dry starch, which is used for later use; weigh the monbuterone and dry starch according to the prescription , Mix membrone with 1/3 of the prescription amount of dry starch for 5 minutes, then add 1/3 of the prescription amount of dry starch, mix for 5 minutes, then add 1/3 of the prescription amount of dry starch, mix for 20 minutes, The mixture is crushed and passed through a No. 5 sieve to get it.

[0018] Quality evaluation indicators and methods: (1) Properties: should be white powder. (2) Appearance uniformity: check according to the method specified under the powder item on page 13 of Appendix One of the Chinese Veterinary Pharmacopoeia (2010 edition). (3) Particle size: Check according to the second method single sieving method in the Chinese Veterinary Pharmacopoeia (2010 edition), page 98 of the particle size and particle size distribution measurement method. (4) Fluidity: Gently pour 50g of veterinary membrone powder into the triangular funnel, open the outflow port at the lower part of the funnel, and measure the time required for all the test products to flow out. Each sample was measured 3 times in succession and the average value was taken. (5) Angle of repose: using the fixed funnel method, three glass funnels are connected in series and fixed at a height of 1 cm above the horizontally placed graph paper, and the veterinary membrone powder is poured into the uppermost funnel along the funnel wall to make it Flow down naturally, until the tip of the powder cone formed on the graph paper touches the mouth of the funnel, the diameter of the bottom of the cone is measured from the graph paper (2R), the angle of repose is calculated: α=arctg (H/R), and the measurement is repeated 3 times, calculate the average value.

[0019] According to the above-mentioned quality evaluation method, the quality evaluation of veterinary membrone powder prepared by the preparation process I to IV was carried out, and the results are shown in Table 1.

[0020] Table 1 Quality evaluation results of veterinary membrone powder prepared by different processes

[0021]

[0022] It can be seen from Table 1: Process I mixes membrone and starch directly. Although the operation is simple and easy, the mixing is not uniform, the appearance uniformity of the powder does not meet the requirements, and the particle size and fluidity are not good, which may be related to starch. The higher water content is related; Process II mixes starch with membrone after drying, the powder has good fluidity, but the appearance uniformity and particle size still do not meet the requirements; Process III mixes starch with membrone step by step after drying, solve To solve the problem of uneven mixing of mumbutone and starch, the appearance uniformity of the powder meets the regulations and the fluidity is good, but the particle size still does not meet the regulations; Process IV mixes the starch with mumbutone step by step after drying, and crushes the mixture , And then sieved, all indexes of the obtained powder meet the requirements. Therefore, the preparation process of veterinary membrone powder is preferably preparation process IV.

[0023] Example 2. Preparation of Mumbutone Powder for Animals (Small Test)

[0024] Prescription: 300g of membrone and 2700g of dry starch.

[0025] Preparation process: Weigh mumbutone and dry starch according to the prescribed amount, put mumbutone into the internal horizontal trough single pulp mixer at one time, add 1/3 of the prescribed amount of dry starch, mix for 5 minutes, and add 1 /3 prescription amount of dry starch, mix for 5 minutes, then add 1/3 prescription amount of dry starch, mix for 20 minutes, put the mixture in a stainless steel universal pulverizer for 5 minutes, pass through a No. 5 sieve, and pack into aluminum-plastic composite In the film packaging bag, 10g per bag, heat-sealed, ready to go.

[0026] According to the above-mentioned prescription and preparation process, 3 batches of veterinary membrone powder samples were prepared in a small test. The results are shown in Table 2.

[0027] Table 2 Preparation of 3 batches of veterinary membrone powder test samples

[0028] Lot number

[0029] According to the provisions of the quality standard (draft) for clinical research of veterinary mumbutone powder, the quality evaluation of the above three batches of small test samples of veterinary mumbutone powder was carried out. The results are shown in Table 3.

[0030] Table 3 The quality evaluation of 3 batches of veterinary membrone powder test samples

[0031]

[0032] The inspection method for related substances of veterinary monbutone powder is as follows: use high performance liquid chromatography to inspect, use octadecylsilane bonded silica as filler, and use 5g/L phosphoric acid solution and acetonitrile in a volume ratio of 1:2 The mixed solution is the mobile phase, and the detection wavelength is 235nm; the number of theoretical plates is not less than 2000 based on the mumbutone peak, and the separation between the mumbutone peak and the adjacent impurity peak is greater than 1.5; accurately weigh the veterinary mumbutone powder 0.5g (equivalent to 50±5mg of mumbutone), dissolve and dilute to 25mL with mobile phase, shake well, accurately measure 5mL, dilute to 50mL with mobile phase, shake well, as the test solution; take precise amount for Test solution 2.0mL, dilute to 100mL with mobile phase, shake well, as a control solution; accurately measure 20μL of the control solution into the liquid chromatograph, adjust the detection sensitivity, so that the peak height of the main component chromatographic peak is 20% of the full scale ~25%; then accurately measure 20μL each of the test solution and the control solution, respectively inject them into the liquid chromatograph, and record the chromatogram; if there is an impurity peak in the test solution chromatogram, the area of ​​the single impurity peak shall not be larger than the main peak of the control solution 0.5 times the area (that is, the content of a single impurity must not be greater than 1.0% of the mumbutone content), and the sum of the peak areas of each impurity must not be greater than the main peak area of ​​the control solution (that is, the total impurity content must not be greater than 2.0% of the mumbutone content). Any peak in the test solution that is less than 0.02 times the main peak area of ​​the control solution is ignored.

[0033] The method for determining the content of veterinary monbutone powder is as follows: Measured by high performance liquid chromatography, mixed with octadecylsilane-bonded silica gel as a filler, and mixed with 5g/L phosphoric acid solution and acetonitrile in a volume ratio of 1:2 The liquid is the mobile phase and the detection wavelength is 235nm. The number of theoretical plates is not less than 2000 calculated based on the mumbutone peak, and the separation between the mumbutone peak and the adjacent impurity peak is greater than 1.5; accurately weigh 0.2g of veterinary mumbutone powder (equivalent to 20±2mg of mumbutone ), use mobile phase to dissolve and dilute to 100mL, shake well, accurately measure 5mL, use mobile phase to dilute to 25mL, shake well, as the test solution; take another reference substance of mumbutone, accurately weigh, use mobile phase Dissolve and dilute quantitatively to make a solution containing 40±4μg per 1mL as the reference solution; accurately measure 20μL each of the test solution and the reference solution into the liquid chromatograph, record the chromatogram, and measure the peak according to the external standard method Calculated by area, the content of membrone should be 90.0% to 110.0% of the labeled amount.

[0034] The above small-scale test results show that three batches of veterinary mumbutone powder were prepared in continuous small-scale trials, and the yields were all above 98%, and the quality of the products obtained all met the requirements of the quality standard (draft) for clinical research of veterinary mumbutone powder This indicates that the preparation process of the veterinary mumbutone powder of the present invention is stable, feasible, and reproducible.

[0035] Example 3. Preparation of mumbutone powder for animals (pilot test)

[0036] Prescription: Mumbutone 3kg, dry starch 27kg.

[0037] Preparation process: Weigh mumbutone and dry starch according to the prescribed amount, put mumbutone into the internal horizontal trough single pulp mixer at one time, add 1/3 of the prescribed amount of dry starch, mix for 5 minutes, and add 1 /3 prescription amount of dry starch, mix for 5 minutes, then add 1/3 prescription amount of dry starch, mix for 20 minutes, put the mixture in a stainless steel universal pulverizer for 5 minutes, pass through a No. 5 sieve, and pack into aluminum-plastic composite In the film packaging bag, 10g per bag, heat-sealed, ready to go.

[0038] According to the above-mentioned prescription and preparation process, three batches of veterinary mumbutone powder samples were prepared in a pilot test. The results are shown in Table 4.

[0039] Table 4 Preparation of 3 batches of veterinary membrone powder pilot test samples

[0040]

[0041]

[0042] According to the provisions of the quality standard (draft) for clinical research of veterinary mumbutone powder, the quality evaluation of the above three batches of veterinary mumbutone powder pilot samples was carried out. The results are shown in Table 5.

[0043] Table 5 Quality evaluation of 3 batches of veterinary membrone powder pilot samples

[0044]

[0045] The above pilot test results prove that the formulation and process of the veterinary membrone powder of the present invention are stable and feasible.