Anti-caking powder of quinocetone and preparation method thereof

Abstract

The present application belongs to the technical field of pesticide preparation, and relates to a cinnamycin anti-caking powder and a preparation method thereof. The present application provides a cinnamycin anti-caking powder which comprises a surfactant, an alkyl coupling agent, seaweed powder, nano-gold modified mercapto cyclodextrin and cinnamycin. The present application solves the technical problem of poor water solubility and stability of cinnamycin by wrapping cinnamycin with nano-gold modified mercapto cyclodextrin, and then wrapping it with a surfactant, an alkyl coupling agent and seaweed powder, reduces the loss of cinnamycin in gastric juice, and prevents the powder from absorbing moisture and caking.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pesticide preparation, and relates to a quinocetone anti-caking powder and a preparation method thereof. BACKGROUND

[0002] Quinocetone is a new national drug officially approved by the Ministry of Agriculture in August 2003, and is a new veterinary drug first created in China. The drug has the characteristics of bacteriostasis, safety in use, rapid metabolism and obvious effect, and is suitable for disease prevention and growth promotion of pigs, poultry, aquatic products, young livestock and young poultry. Quinocetone has poor solubility and is easy to absorb moisture and cake. Generally, the drug is administered by mixing with feed, which has the disadvantages of low bioavailability and poor absorption. The above defects limit the application of quinocetone in veterinary drugs, and it is urgent to develop a quinocetone anti-caking powder which meets the requirements of solubility and stability.

[0003] At present, the dosage form of commercially available quinocetone cannot meet the requirements of solubility and stability. For example, CN105878186A provides a water-soluble powder preparation of quinocetone cyclodextrin inclusion compound and a preparation method thereof. The quinocetone and cyclodextrin mixed preparation solves the problem of water solubility of quinocetone. Quinocetone is administered by mixing with feed, and the cyclodextrin will be cleaved in the stomach. The inclusion structure of the quinocetone cyclodextrin inclusion compound will be destroyed, and the retention time of the product in the intestinal tract cannot be guaranteed. The bioavailability improvement rate is limited, and the problem of easy moisture absorption and caking cannot be solved.

[0004] Quinocetone is excreted quickly and has a short half-life. Multiple administrations are required to achieve the desired therapeutic effect, which not only consumes a large amount of manpower, but also causes multiple stresses to the diseased animals. Therefore, it is necessary to provide a quinocetone preparation to improve the solubility and stability of quinocetone, reduce the loss of quinocetone in gastric juice, and ensure the retention time of quinocetone in the intestinal tract. SUMMARY

[0005] The purpose of the present application is to solve the problems of poor solubility and stability of quinocetone.

[0006] Based on the above purpose, the present application provides a quinocetone anti-caking powder and a preparation method thereof to meet the needs in the field.

[0007] In one aspect, the present application relates to a preparation method of a quinocetone anti-caking powder, which comprises:

[0008] S1: Dissolve HAuCl4 and mercapto-β-cyclodextrin in water respectively, then mix at 80-90℃, adjust the pH to 7.5-8, and incubate and stand for 30-60min to obtain a nanogold modified mercapto cyclodextrin solution, add quinocetone, adjust the pH to 6-6.5, and rapidly stir for 20-40min, and incubate and stand for 8-15min;

[0009] S2: the liquid prepared in S1 is mixed with a surfactant and seaweed powder, and then an alkyl coupling agent is added dropwise, and the mixture is reacted at 40-60 DEG C while slowly stirring for 1-1.5 h;

[0010] S3: the liquid prepared in S2 is vacuum dried at 90-105 DEG C for 3-4 h to prepare the anti-caking powder of quinocetone.

[0011] Further, in the preparation method of the anti-caking powder of quinocetone, the mass ratio of HAuCl4 to mercapto-beta-cyclodextrin is 1:20-30.

[0012] The preparation method comprises the following steps: 100 parts of quinocetone, 300-600 parts of mercapto-beta-cyclodextrin, 1-10 parts of a surfactant, 1-3 parts of an alkyl coupling agent, and 40-80 parts of seaweed powder are mixed.

[0013] Further, in the preparation method of the anti-caking powder of quinocetone, the surfactant is sodium dodecyl sulfonate or sodium dodecyl sulfate.

[0014] Further, in the preparation method of the anti-caking powder of quinocetone, the alkyl coupling agent is gamma-(ethylenediamino) propyl trimethoxysilane.

[0015] Further, in the preparation method of the anti-caking powder of quinocetone, the stirring speed of the fast stirring is 400-800 r / min.

[0016] The stirring speed of the slow stirring is 80-150 r / min.

[0017] In another aspect, the present application relates to an anti-caking powder of quinocetone prepared by the above preparation method.

[0018] Compared with the prior art, the present application has the following advantages:

[0019] The hollow cone-shaped structure with hydrophobic inside and hydrophilic outside is formed by the gold cluster outside the cyclodextrin group, and has good packaging effect on quinocetone. The nano gold has no toxic effect on the organism, and under the action of nano gold and mercapto group, the absorption efficiency of the intestinal mucosal epithelial cell membrane can be improved, the loss of quinocetone in gastric juice can be reduced, and the residence time of quinocetone in the intestinal tract can be ensured. The surfactant, alkyl coupling agent and seaweed powder are used for re-wrapping. Under the action of the alkyl coupling agent, the silane reacts with the surface water, is hydrolyzed to form a silicon carboxyl group, and then forms a hydrogen bond or a covalent bond with the surface hydroxyl group, and a reticular structure film is formed, so that the dispersibility, moisture resistance and degradation of quinocetone by light are improved, and the loss of quinocetone in gastric juice is reduced. DETAILED DESCRIPTION

[0020] The technical solutions of the present application will be described in detail below in combination with specific embodiments. The following embodiments will help those skilled in the art to further understand the present application, but do not limit the present application in any form. It should be pointed out that those skilled in the art can make several modifications and improvements without departing from the concept of the present application. These all belong to the protection scope of the present application.

[0021] The experimental methods and detection methods described in the following embodiments are all conventional methods unless otherwise specified; the reagents and materials described are all commercially available unless otherwise specified.

[0022] Example 1

[0023] This embodiment provides the preparation of the anti-caking powder of quinocetone.

[0024] Test raw material source: quinocetone is purchased from Shandong Suitai Biological Technology Co., Ltd., mercapto-β-cyclodextrin is purchased from Shanghai Dibo Biological Technology Co., Ltd., and arthrospira platensis powder, dunaliella salina powder and chlorella vulgaris powder are purchased from Dongtaish City Cibainian Biological Engineering Co., Ltd.

[0025] Test steps:

[0026] (1) Under the condition of 80℃, 100mL of HAuCl4 aqueous solution (15mg / mL) is taken and stirred vigorously for 10min, 100mL of mercapto-β-cyclodextrin solution (300mg / mL) is added, NaOH solution (0.5M) is added to adjust the pH to 7.5, and the solution is incubated and placed for 30min to obtain a nano gold modified mercapto cyclodextrin solution. Then 10g of quinocetone is added, and HCl (0.5M) is used to adjust the pH to 6, 400r / min stirring is carried out for 20min, and incubation and standing are carried out for 8min to prepare liquid 1.

[0027] (2) Add 0.1g sodium dodecyl sulfonate and 4g Spirulina platensis powder to liquid 1, stir for 15min, and add 0.1g γ-(ethylenediamino)propyltrimethoxysilane at a rate of 0.5 drops / s at 40℃. Keep warm and stir at a rate of 80r / min for 1h to obtain liquid 2.

[0028] (3) Place liquid 2 in a vacuum drying oven and dry at 90°C for 3 hours. Pass it through an 80-mesh sieve to obtain the anti-caking powder of quinolone.

[0029] Example 2

[0030] This embodiment provides the preparation of anti-caking powders of quinones with different formulations.

[0031] Experimental steps:

[0032] (1) At 85℃, 100 mL of HAuCl4 aqueous solution (18 mg / mL) was stirred vigorously for 10 min, 100 mL of mercapto-β-cyclodextrin solution (450 mg / mL) was added, and NaOH solution (0.5 M) was added to adjust the pH to 7.7. The solution was kept warm and allowed to stand for 45 min to obtain a mercapto-cyclodextrin solution modified with gold nanoparticles. 10 g of quinone was added, and then the pH was adjusted to 6.3 with HCl (0.5 M). The solution was stirred at 600 r / min for 30 min, kept warm and allowed to stand for 10 min to obtain liquid 1.

[0033] (2) Add 0.5g sodium dodecyl sulfonate and 6g Haematococcus pluvialis powder to liquid 1, stir for 15min, add 0.2g γ-(ethylenediamino)propyltrimethoxysilane at a rate of 0.5 drops / s at 50℃, keep warm and stir at a rate of 100r / min for 1.2h to obtain liquid 2.

[0034] (3) Place liquid 2 in a vacuum drying oven and dry at 100°C for 3.5 hours. Pass it through an 80-mesh sieve to obtain the anti-caking powder of quinolone.

[0035] Example 3

[0036] This embodiment provides the preparation of anti-caking powders of quinones with different formulations.

[0037] Experimental steps:

[0038] (1) 100 mL of HAuCl4 aqueous solution (20 mg / mL) was stirred vigorously for 10 min at 90℃, 100 mL of thiol-β-cyclodextrin solution (600 mg / mL) was added, NaOH solution (0.5 M) was added to adjust the pH to 8, and the solution was incubated and left standing for 60 min to obtain a nanogold modified thiol cyclodextrin solution. Then 10 g of queinoctone was added, and HCl (0.5 M) was used to adjust the pH to 6.5. The solution was stirred at 800 r / min for 40 min, incubated and left standing for 15 min, and liquid 1 was prepared.

[0039] (2) 1.0 g of sodium dodecyl sulfate and 8 g of Chlorella pyrenoidosa powder were added to liquid 1, stirred for 15 min, and 0.3 g of γ-(ethylenediamino) propyl trimethoxysilane was added dropwise at a speed of 0.5 drops / s at 60℃, and the solution was incubated and stirred at a speed of 150 r / min for 1.5 h to prepare liquid 2.

[0040] (3) Liquid 2 was placed in a vacuum drying oven and dried at 105℃ for 4 h, and then sieved through an 80-mesh sieve to obtain the anti-caking powder of queinoctone.

[0041] Comparative Example 1

[0042] This comparative example provides a preparation comparison of the anti-caking powder of queinoctone. The preparation method of this comparative example is the same as that of Example 2, except that no seaweed powder is added.

[0043] Comparative Example 2

[0044] This comparative example provides a preparation comparison of the anti-caking powder of queinoctone. The preparation method of this comparative example is the same as that of Example 2, except that no alkyl coupling agent is added.

[0045] Comparative Example 3

[0046] This comparative example provides a preparation comparison of the anti-caking powder of queinoctone. The preparation method of this comparative example is the same as that of Example 2, except that no alkyl coupling agent is added.

[0047] Example 4

[0048] This example provides the test results of the dispersibility and anti-caking performance of the anti-caking powder of queinoctone prepared in the above examples and comparative examples.

[0049] Dispersibility performance test: 5 g of the anti-caking powder of queinoctone and 20 g of ethanol were stirred in a stirrer for 2 min, and then filtered through a 200-mesh sieve. The residue was baked at 100℃ for 1 h, and the mass was measured. The less the residue, the better the dispersibility.

[0050] Anti-caking performance test: temperature 25℃, humidity 90%. 5g of the anti-caking powder of quinocetone was placed in a 100ml beaker (previously 80 mesh sieve, 100% sieve pass). After 20h and 200h in the constant temperature and humidity box according to the above conditions, sieve pass with 80 mesh sieve, the mass of quinocetone anti-caking powder that did not pass the sieve was weighed, and the ratio to the total mass was the caking percentage. The test results are shown in Table 1.

[0051] Table 1 Dispersibility and anti-caking performance test results

[0052]

[0053] As can be seen from Table 1, by using the nano-gold modified mercapto cyclodextrin to wrap quinocetone, and using surfactants, alkyl coupling agents, and seaweed powder for further wrapping, the dispersibility of the quinocetone preparation can be effectively improved, and there is no change in the moisture test for 20h, and the agglomeration and caking is about 10% for 200h.

[0054] Example 5

[0055] This example provides the test results of the anti-caking powder of quinocetone prepared in the above examples and comparative examples in simulated gastric juice.

[0056] Take concentrated hydrochloric acid with a concentration of 1mol / mL, dilute with water, adjust the pH to 2.0, add 1g of pepsin per 100ml of liquid, mix well, filter with a 0.2μm sterile filter head, and prepare the simulated gastric juice. The anti-caking powder of quinocetone prepared in the above examples and comparative examples was placed in the simulated gastric juice for 0-2h, then the pH was adjusted to 5.0 for 2-4h, and finally the pH was adjusted to 7.0 for 4-10h, and the cumulative release amount was counted. The test results are shown in Table 2.

[0057] Table 2 Cumulative release amount (%) test results

[0058]

[0059]

[0060] As can be seen from Table 2, the seaweed powder provides good resistance to gastric acid, and the surfactant, alkyl coupling agent, and seaweed powder are further wrapped. Under the action of the alkyl coupling agent, the silane reacts with the surface moisture, hydrolyzes to form silane carboxyl, and then forms hydrogen bonds or condenses into covalent bonds with the surface hydroxyl group, and oligomerizes to form a network structure film, which provides a basic structure for the seaweed powder on the surface. The present application can reduce the loss of quinocetone in the gastric juice and ensure the residence time of quinocetone in the intestinal tract.

[0061] As described above, the application can be realized well, the above-mentioned embodiments are only used to describe the preferred embodiments of the application, and do not limit the scope of the application, and various changes and improvements of the technical solutions of the application made by those skilled in the art without departing from the design spirit of the application shall fall within the scope of protection of the application.

Claims

1. A method for preparing an anti-caking powder of quinocetone, characterized by, The preparation method comprises the following steps: S1: dissolving HAuCl4 and mercapto-β-cyclodextrin in water respectively, then mixing them at 80-90 DEG C, adjusting pH to 7.5-8, and standing for 30-60 min to obtain a nano gold modified mercapto cyclodextrin solution, adding quinocydine, adjusting pH to 6-6.5, and stirring rapidly for 20-40 min, and standing for 8-15 min; S2: mixing the surfactant, seaweed powder and the liquid prepared in S1, then dropping alkyl coupling agent, and reacting at 40-60 DEG C while stirring slowly for 1-1.5 h; S3: drying the liquid prepared in S2 at 90-105 DEG C in vacuum for 3-4 h to obtain the anti-caking powder of quinocydine.

2. The method of preparing the coccidian anticaking powder of quinoxaline ketone according to claim 1, characterized by, The mass ratio of HAuCl4 to mercapto-β-cyclodextrin is 1:20-30. The preparation method comprises the following steps: quinocydine 100 parts, mercapto-β-cyclodextrin 300-600 parts, surfactant 1-10 parts, alkyl coupling agent 1-3 parts, and seaweed powder 40-80 parts.

3. The method of preparing the coccidian anticaking powder of quinoxaline ketone according to claim 1, characterized by, The surfactant is sodium dodecyl sulfonate or sodium dodecyl sulfate.

4. The method of preparing the coccidian anticaking powder of quinoxaline ketone according to claim 1, characterized by, The alkyl coupling agent is γ-(ethylenediamine) propyl trimethoxysilane.

5. The method of preparing the coccidian anticaking powder of quinoxaline according to claim 1, characterized by, The stirring rate of the rapid stirring is 400-800 r / min. The stirring rate of the slow stirring is 80-150 r / min.

6. An anti-caking powder of quinocetone, characterized by, The anti-caking powder of quinocydine is prepared by the preparation method of any one of claims 1-5.

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