Preparation method of high-water-solubility menbutone powder

Abstract

The invention relates to a preparation method of menbutone powder, the menbutone powder comprises menbutone, a cosolvent, a protective agent and a filler, and the preparation method is characterized by comprising the following steps: step 1, preparing the protective agent into a solution; 2, placing menbutone in a fluidized bed to boil the powder, and adding the solution prepared from the protective agent in the step 1; and step 3, taking out after drying, and uniformly mixing with the cosolvent and the filler. The menbutone powder obtained by the preparation method has the characteristics of high water solubility, high activity, high stability under the conditions of high temperature, high humidity or illumination, and difficult generation of impurities after long-term storage.

Description

Technical Field

[0001] The invention belongs to the field of preparation of pharmaceutical compositions, and specifically relates to highly water-soluble menbutone powder. Background Art

[0002] The intensive breeding model adopts fully enclosed management, strict disease prevention and control measures, and scientific management procedures. Compared with farmers' free-range breeding, it has high production efficiency and is basically not affected by external environmental conditions and seasons, which is conducive to continuous production throughout the year, thereby providing a stable supply to the market. However, with the application of intensive breeding models, a series of new problems have emerged. In order to adapt to group prevention, group medication, and centralized drinking water medication have become the first choice for large-scale intensive breeding. This has put forward new requirements for the water solubility of solid powder veterinary drugs. Improving the water solubility of the product and facilitating clinical use on the breeding side directly determine the competitiveness of the product in the market.

[0003] Menbutrone is a commonly used drug. The present invention upgrades the prescription process on the basis of the original menbutrone powder to create a new soluble menbutrone powder, which has stable preparation properties, good water solubility, is convenient for clinical use, and has a clinical effect that is significantly better than that of ordinary preparations. Summary of the invention

[0004] The purpose of the present invention is to overcome the defects of the prior art. According to the properties of the raw material of Menbutone, the raw material particle size of Menbutone is below 500 microns, has no crystallinity, and its water solubility increases with the increase of pH. When the pH is greater than 9, the ester bond in the structure of Menbutone is very easy to hydrolyze, and the carboxyl group in the structure of Menbutone itself can react with most alkaline substances, and the covalent salt formed is extremely unstable, and the degradation product has no choleretic activity. The solubility-aiding alkali selected in the present invention is processed to avoid direct reaction with Menbutone, and the purpose of improving water solubility is achieved under the premise of retaining the activity of the Menbutone component.

[0005] In order to achieve the above object, the present invention provides a method for preparing menbutone powder, wherein the menbutone powder comprises menbutone, a cosolvent, a protective agent and a filler, and the preparation method comprises the following steps:

[0006] Step 1: preparing the protective agent into a solution;

[0007] Step 2: Place Menbutone in a fluidized bed, boil the powder, and add the solution prepared by the protective agent in step 1;

[0008] Step 3: Take out after drying and mix evenly with co-solvent and filler.

[0009] Preferably, in step 1, the protective agent includes at least one of stearic acid, polyethylene glycol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, and copovidone.

[0010] Preferably, in any of the above items, in step 1, the concentration of the protective agent in the solution is 5-10 w / v%.

[0011] Preferably, in any of the above items, in step 1, the protective agent is prepared into a solution of 0.5-2 w / v% stearic acid solution. The preferred concentration of stearic acid is 0.5, 1, 1.5, 2 w / v% and the range therebetween.

[0012] Preferably, in any of the above items, in step 1, the protective agent is prepared into a solution of 1-5 w / v% polyethylene glycol solution. The preferred concentration of the polyethylene glycol is 1, 2, 3, 4, 5 w / v% and the range therebetween.

[0013] Preferably, in any of the above items, in step 1, the protective agent is prepared into a solution of 1-10 w / v% hydroxypropyl methylcellulose. The preferred concentration of the hydroxypropyl methylcellulose is 1, 3, 5, 7, 10 w / v% and the range therebetween.

[0014] Preferably, in any of the above items, in step 1, the protective agent is prepared into a solution of 1-10 w / v% hydroxypropyl cellulose. The preferred concentration of the hydroxypropyl cellulose is 1, 3, 5, 7, 10 w / v% and the range therebetween.

[0015] Preferably, in any of the above items, in step 1, the protective agent is prepared as a solution of 5-15 w / v% polyvidone solution. The preferred concentration of the polyvidone is 5, 10, 15 w / v% and the range therebetween.

[0016] Preferably, in any of the above items, in step 1, the protective agent is prepared into a solution of 5-15 w / v% copovidone solution. The preferred concentration of the copovidone is 5, 10, 15 w / v% and the range therebetween.

[0017] In any of the above, preferably, in step 1, the protective agent is prepared with water as the solvent or ethanol-water solution as the solvent. In any of the above, preferably, in step 2, the fluidized bed setting parameters are: air volume 100-150m 3 / h; Inlet air temperature: 40-60℃; Peristaltic pump flow rate 25ml / h; Atomization pressure 1-2bar.

[0018] Preferably, in step 2, the fluidized bed setting parameters are: air volume of 100, 120, 150m 3 / h and its range.

[0019] Preferably, in step 2, the fluidized bed setting parameters are: the inlet air temperature is 40, 45, 50, 55, 60°C and the range therebetween.

[0020] Preferably, in step 2, the fluidized bed setting parameters are: peristaltic pump flow rate 25 ml / h.

[0021] Preferably, in step 2, the fluidized bed setting parameters are: the atomization pressure is 1 or 2 bar.

[0022] Preferably, in any of the above items, in step 2, the particle size of the menbutone is less than 500 microns.

[0023] Preferably, in any one of the above items, in step 3, the co-solvent is a dissolving base.

[0024] Any of the above is preferably that in step 3, the co-solvent includes at least one of sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, sodium citrate, sodium phosphate, sodium caprylate, and sodium caprate.

[0025] Preferably, in any of the above items, in step 3, the filler comprises at least one of glucose, sucrose, lactose, trehalose, mannitol, microcrystalline cellulose, disodium hydrogen phosphate, and sodium phosphate.

[0026] Preferably, any of the above items is that the Menbutone powder comprises the following components in the following mass ratios: 1-10 parts of Menbutone, 3-6 parts of co-solvent, 1-2 parts of protective agent, and 2-15 parts of filler.

[0027] The present invention also provides a Menbutone powder composition prepared according to any one of the above-mentioned Menbutone powder preparation methods. The Menbutone powder obtained by the preparation method of the present invention is a novel Menbutone powder composition with high water solubility.

[0028] Preferably, the Menbutone powder composition contains the following components in the following mass ratios: Menbutone accounts for 1-10 parts, the co-solvent accounts for 3-6 parts, the protective agent accounts for 1-2 parts, and the filler accounts for 2-15 parts.

[0029] Preferably, Menbutone accounts for 1, 5, 10 parts and the range therebetween;

[0030] Preferably, the cosolvent accounts for 3, 4, 5, 6 parts and the range therebetween;

[0031] Preferably, the protective agent accounts for 1 or 2 parts and the range therebetween;

[0032] Preferably, the filler accounts for 2, 5, 10, 15 parts and ranges therebetween.

[0033] Preferably, in any of the above items, the co-solvent comprises at least one of alkaline co-solvents such as sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, sodium citrate, sodium phosphate, sodium caprylate, and sodium caprate.

[0034] Preferably, in any of the above items, the protective agent comprises at least one of stearic acid, polyethylene glycol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copovidone and the like.

[0035] Preferably, the filler mainly includes: glucose, sucrose, lactose, trehalose, mannitol, microcrystalline cellulose, disodium hydrogen phosphate, sodium phosphate and the like.

[0036] Preferably, the process for preparing the highly water-soluble Menbutone powder composition is as follows: preparing a protective agent into a suitable solution; placing Menbutone in a fluidized bed, boiling the powder, adding the solution prepared with the protective agent at a suitable speed, taking it out after complete drying, and mixing it evenly with the co-solvent and the filler.

[0037] The menbutone powder obtained by the preparation method of the present invention has the characteristics of high water solubility, high activity, high stability under high temperature, high humidity or light conditions, and is not prone to produce impurities during long-term storage. DETAILED DESCRIPTION

[0038] The present invention is further described in detail below through specific implementation modes.

[0039] Example 1

[0040] Prescription: 1 part of Menbutone, 3 parts of sodium hydroxide, 1 part of polyethylene glycol, and 15 parts of lactose.

[0041] Process: 1. Add polyethylene glycol and hot water to prepare a 10% solution.

[0042] 2. Add Menbutone into the fluidized bed and set the air volume to 100-150m 3 / h; inlet air temperature: 40-60℃; peristaltic pump flow rate 25ml / h; atomization pressure 1-2bar; complete boiling, bottom spray adding polyethylene glycol solution.

[0043] 3. Take out after drying for 30 minutes and mix thoroughly with sodium hydroxide and lactose.

[0044] Example 2

[0045] Prescription: 5 parts of Menbutone, 4 parts of sodium carbonate, 1 part of povidone, and 10 parts of sucrose.

[0046] Process: 1. Add water to povidone to prepare a 7% solution.

[0047] 2. Add Menbutone into the fluidized bed and set the air volume to 100-150m 3 / h; inlet air temperature: 40-60℃; peristaltic pump flow rate 25ml / h; atomization pressure 1-2bar; complete boiling, bottom spray adding povidone solution.

[0048] 3. Take out after drying for 30 minutes and mix thoroughly with sodium carbonate and sucrose.

[0049] Example 3

[0050] Prescription: 10 parts of Menbutone, 6 parts of sodium citrate, 2 parts of hydroxypropyl methylcellulose, and 10 parts of trehalose.

[0051] Process: 1. Add water to hydroxypropyl methylcellulose to prepare a 5% solution.

[0052] 2. Add Menbutone into the fluidized bed and set the air volume to 100-150m 3 / h; inlet air temperature: 40-60℃; peristaltic pump flow rate 25ml / h; atomization pressure 1-2bar; complete boiling, bottom spray adding hydroxypropyl methylcellulose solution.

[0053] 3. Take out after drying for 30 minutes and mix thoroughly with sodium citrate and trehalose.

[0054] Example 4

[0055] Example 4 is similar to Examples 1, 2, and 3, except that the cosolvent is selected from one of alkaline cosolvents such as sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, sodium citrate, sodium phosphate, sodium caprylate, and sodium caprate; the protective agent is selected from at least one of stearic acid, polyethylene glycol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, copolyvidone, etc. The filler is selected from one of glucose, sucrose, lactose, trehalose, mannitol, microcrystalline cellulose, disodium hydrogen phosphate, and sodium phosphate. Since the Menbutone powder obtained in Example 4 has the same technical effect as the Menbutone powder obtained in Examples 1, 2, and 3, that is, it is highly water-soluble and highly active, and has high stability under high temperature, high humidity or light conditions, and is not easy to produce impurities for long-term storage. Therefore, taking Examples 1, 2, and 3 as examples, subsequent comparative tests are carried out with the comparative examples.

[0056] Comparative Example 1

[0057] Prescription: 1 part of Menbutone and 9 parts of anhydrous glucose.

[0058] Process: Direct mixing

[0059] Comparative Example 2

[0060] Prescription: 5 parts of Menbutone, 4 parts of sodium carbonate, 1 part of povidone, and 10 parts of sucrose.

[0061] Process: Direct mixing

[0062] Example 5

[0063] Table 1 shows the water solubility comparison of the Menbutone powder obtained in Examples 1-3 and the Menbutone powder obtained in Comparative Examples 1 and 2. At room temperature 25±5°C, 1 g of Menbutone powder was dissolved in water in different volumes of water.

[0064] Table 1:

[0065] name Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 1g to 500ml water Completely dissolved Completely dissolved Completely dissolved Undissolved Completely dissolved 1g to 100ml water Completely dissolved Completely dissolved Completely dissolved Undissolved Completely dissolved 1g to 50ml water Completely dissolved Completely dissolved Completely dissolved Undissolved Completely dissolved 1g to 25ml water Completely dissolved Mostly dissolved Partially dissolved Undissolved Mostly dissolved

[0066] Example 6

[0067] Table 2 shows the results of the study on the influencing factors of the menbutone powder obtained in Examples 1-3 and the menbutone powder obtained in Comparative Examples 1 and 2. The data in the table are the percentage of the mass of menbutone in the obtained menbutone powder to the labeled amount.

[0068] Table 2:

[0069]

[0070]

[0071] Example 7

[0072] The clinical use of the Menbutron powder obtained in Example 2 and the Menbutron powder obtained in Comparative Example 2 is summarized.

[0073] Experimental subjects: 60 20-day-old piglets were randomly divided into 3 groups, with 20 pigs in each group.

[0074] The experimental grouping was set up as follows: Group 1 was administered with the prescription drug of Example 2; Group 2 was administered with the prescription drug of Comparative Example 2; and Group 3 was administered with plain water.

[0075] Test method: The three groups of piglets were given drugs respectively, with a dosage of 10 mg per kg body weight, once every 7 days, for 3 times. The average weight gain of each test group was observed and recorded. The specific results are shown in Table 3.

[0076] Table 3: Experimental results:

[0077] name Initial total weight Total weight for 7 days Total weight on 14 days Total weight on 21 days Average weight gain in 21 days 1 group 104.6kg 131.6kg 169.1kg 228.7kg 6.205kg 2 groups 105.1kg 127.8kg 161.3kg 209.4kg 5.215kg 3 groups 104.7kg 126.2kg 158.2kg 203.9kg 4.915kg

[0078] Experimental conclusion: From the experimental results, it can be seen that taking Menbutone powder has a significant weight gain advantage over the blank group for piglets, and there are also differences in weight gain between different Menbutone powder preparations. The average weight gain of the comparative example 2 preparation of the present invention is 6.205 kg on 21 days, which is significantly better than the weight gain data of the comparative example group and the blank group. It proves that the Menbutone powder preparation of the present invention has a significant advantage over the ordinary Menbutone powder preparation.

[0079] The above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the scope of protection of the invention.

Claims

1. A method for preparing menbutone powder, the menbutone powder comprising menbutone, a cosolvent, a protective agent and a filler, characterized in that: The preparation method comprises the following steps: Step 1: preparing the protective agent into a solution; Step 2: Place Menbutone in a fluidized bed, boil the powder, and add the solution prepared by the protective agent in step 1; Step 3: Take out after drying and mix evenly with co-solvent and filler.

2. The method for preparing menbutone powder according to claim 1, characterized in that: In step 1, the protective agent includes at least one of stearic acid, polyethylene glycol, hydroxypropyl methylcellulose, hydroxypropyl cellulose, povidone, and copovidone.

3. The method for preparing menbutone powder according to claim 2, characterized in that: In step 1, the concentration of the solution prepared by the protective agent is one of: stearic acid 0.5-2w / v%, polyethylene glycol 1-5w / v%, hydroxypropyl methylcellulose 1-10w / v%, hydroxypropyl cellulose 1-10w / v%, povidone 5-15w / v%, and copovidone 5-15w / v%.

4. The method for preparing Menbutone powder according to claim 1, wherein In step 2, the fluidized bed setting parameters are: air volume 100-150m 3 / h; Inlet air temperature: 40-60℃; Peristaltic pump flow rate 25ml / h; Atomization pressure 1-2bar.

5. The method for preparing Menbutone powder according to claim 1, characterized in that: In step 2, the particle size of the menbutone is less than 500 microns.

6. The method for preparing menbutone powder according to claim 1, characterized in that: In step 3, the co-solvent is an alkaline reagent.

7. The method for preparing Menbutone powder according to claim 6, characterized in that: In step 3, the co-solvent includes at least one of sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, sodium citrate, sodium phosphate, sodium caprylate, and sodium caprate.

8. The method for preparing menbutone powder according to claim 1, characterized in that: In step 3, the filler includes at least one of glucose, sucrose, lactose, trehalose, mannitol, microcrystalline cellulose, disodium hydrogen phosphate, and sodium phosphate.

9. The method for preparing Menbutone powder according to any one of claims 1 to 8, characterized in that: The Menbutone powder comprises the following components in the following mass proportions: 1-10 parts of Menbutone, 3-6 parts of co-solvent, 1-2 parts of protective agent and 2-15 parts of filler.

10. A Menbutone powder composition prepared according to the Menbutone powder preparation method according to any one of claims 1 to 9.

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