Disclosure of Invention
In order to reduce the caking probability of the powdery medicaments, the application provides an auxiliary agent for effectively preventing the hymexazol from caking.
In a first aspect, the application provides an auxiliary agent for effectively preventing hymexazol from caking, which adopts the following technical scheme:
an auxiliary agent for effectively preventing hymexazol from caking comprises, by weight, 100-130 parts of hydroxyethyl cellulose, 80-90 parts of sodium alginate, 15-30 parts of polyethylene glycol, 20-40 parts of inorganic powder and 30-50 parts of a surfactant.
By adopting the technical scheme, the inorganic powder has the characteristics of fine particles, low density and strong adhesive force, has the functions of mechanical isolation and absorbing moisture on the surfaces of the particles, can prevent the formation of bonding points among the grains, and effectively prevents the powder from caking. However, if the inorganic powder is used for anti-caking of hymexazol, the amount of the inorganic powder is large, and the effect of the inorganic powder alone is poor, so that the dust content of the hymexazol is increased.
Hydroxyethyl cellulose is a derivative of cellulose, is prepared from alkali cellulose and ethylene oxide through etherification reaction, and belongs to nonionic soluble cellulose ethers. The hydroxyethyl cellulose has good film forming property, wide range of solubility, nonionic property and other water-soluble polymers such as surfactant in a wide range, and can be interacted to form a compound, so that the property of the hydroxyethyl cellulose and the water-soluble polymer are mutually modified, the surface activity of an aqueous solution system is improved, and the dispersibility of the surfactant is enhanced.
The hydroxyethyl cellulose is firmly bonded outside the hymexazol to form a layer of tough solid film, a channel for water transmission is cut off, and the hymexazol particles are mechanically isolated, so that the water exchange between the hymexazol and the atmosphere is blocked, the dissolution and recrystallization processes of the crystal surface are inhibited, the generation of crystal bridges is prevented, and the anti-caking performance of the product is improved. In addition, hydroxyethyl cellulose is a water-absorbing substance, and once the surface of the hymexazol has more moisture, the moisture is adsorbed, so that the resolubilization of the hymexazol crystal is avoided.
Hydroxyethyl cellulose is used as a main film forming substance, sodium alginate and polyethylene glycol are compounded to form a film on the surface of hymexazol particles, the film forming process is promoted, the film forming quality and efficiency are improved, and inorganic powder and a surfactant are inlaid in the film forming process. So that the inorganic powder can be uniformly dispersed outside the hymexazol to be matched with the surfactant to prevent the hymexazol from caking.
Further, the inorganic powder comprises one or more of talcum powder, kaolin, bentonite and diatomite.
By adopting the technical scheme, the talcum powder has good lubricity and dispersibility, can reduce friction force between the powder and reduce caking phenomenon of the powder in the storage and transportation processes. Kaolin is a clay mineral of fine particle size, and has good adsorptivity and dispersibility. In the aspect of powder anti-caking, the kaolin can adsorb moisture on the surface of the powder, and reduce adhesion among powder particles, thereby preventing caking. Bentonite is a clay mineral with high water absorbability and expansibility, and the main component is montmorillonite. In the aspect of powder anti-caking, bentonite can absorb moisture and expand to form an isolating layer, and powder particles are prevented from being in direct contact, so that caking is reduced. Diatomaceous earth is a porous material composed of diatomaceous fossil, and has high porosity and large specific surface area. In the aspect of powder anti-caking, the diatomite can provide additional surface area, adsorb moisture and grease on the surface of the powder, reduce the adhesion among particles and prevent caking. These inorganic powders can be used in the anti-caking agent of the present application to reduce the chance of hymexazol caking.
Further, the inorganic powder comprises talcum powder and bentonite in a weight ratio of 2 (3-5).
Further, the particle size of the talcum powder is 0.5-1.5 mu m, and the particle size of the bentonite is 3-5 mu m.
By adopting the technical scheme, the variety and the grain composition of the inorganic powder are limited, and the anti-caking effect of the hymexazol is further improved.
Further, the surfactant comprises at least one of sodium dodecyl benzene sulfonate and ammonium stearate.
Further, the surfactant comprises sodium dodecyl benzene sulfonate and ammonium stearate in a weight ratio of (2-3): 1.
By adopting the technical scheme, the sodium dodecyl benzene sulfonate can improve the smoothness of the wrapping film, reduce the friction force among particles, regulate the hygroscopicity of the particles and prevent the particles from absorbing excessive moisture to cause caking. Ammonium stearate is a surfactant capable of forming a hydrophobic protective film on the surface of particles, which film reduces the attractive interaction between the particles and reduces the adhesion of the particles, thereby preventing agglomeration. The anti-caking effect on the hymexazol can be improved to a greater extent by the combination of the two.
Further, the hydroxyethyl cellulose is modified hydroxyethyl cellulose, and the modification method comprises the following steps:
Dispersing hydroxyethyl cellulose in the dispersion liquid, adding sodium hydroxide solution to enable the hydroxyethyl cellulose to be fully swelled, then adding bromooctadecane, reacting at 80-85 ℃, cooling after the reaction is finished, soaking the product in n-hexane, filtering to obtain a precipitate, and cleaning and drying the precipitate to obtain the modified hydroxyethyl cellulose.
Further, the weight ratio of the hydroxyethyl cellulose to the bromooctadecane is 10 (7-9).
By adopting the technical scheme, the long carbon chain is grafted on the hydroxyethyl cellulose, and the hydroxyethyl cellulose is subjected to hydrophobic modification, so that the hydroxyethyl cellulose simultaneously contains hydrophilic groups and hydrophobic groups, and the nano micelle with a core-shell structure can be formed in an aqueous solution through a self-assembly technology. The content of ether bond and alkane structure in the polymer is increased, the hydrophobic effect of the polymer is improved, the micelle structure formed by dispersing the polymer in water is tighter, the particle size is reduced, the self-assembly capability of the polymer is improved, and the entrapment capability of hymexazol is further improved.
In a second aspect, the application provides an application of an auxiliary agent for effectively preventing hymexazol from caking, which adopts the following technical scheme;
An application of an auxiliary agent for effectively preventing hymexazol from caking is provided, which is applied to hymexazol.
Further, the auxiliary agent capable of effectively preventing the hymexazol from caking is dissolved in water to obtain mixed solution, the mixed solution is sprayed on the surface of the hymexazol, and then the mixed solution is dried, so that the auxiliary agent capable of effectively preventing the hymexazol from caking forms a film and wraps the surface of the hymexazol.
By adopting the technical scheme, the effective wrapping film is formed outside the hymexazol, so that the anti-caking effect of the hymexazol is improved.
In summary, the application has the following beneficial effects:
1. The method comprises the steps of preparing an auxiliary agent for effectively preventing the hymexazol from caking by using hydroxyethyl cellulose, sodium alginate and polyethylene glycol as film forming substances and using inorganic powder and a surfactant as functional additives, wherein the auxiliary agent for effectively preventing the hymexazol from caking is used for the hymexazol, and an isolating film is arranged outside the hymexazol, so that the caking rate of the obtained hymexazol after 10 days of a caking experiment is as low as 5.1-0.6%, the caking rate after 20 days of the caking experiment is as low as 5.6-0.7%, and the anti-caking effect of the hymexazol is greatly improved.
2. The hydroxyethyl cellulose is modified by bromooctadecane, so that the anti-caking effect of the hymexazol is further improved, the caking rate of the obtained hymexazol after 10 days of caking experiments is as low as 1.9-0.6%, the caking rate after 20 days of caking experiments is as low as 2.1-0.7%, and the anti-caking effect of the hymexazol is greatly improved.
Detailed Description
The present application will be described in further detail with reference to examples.
Preparation of starting materials and intermediates
Raw materials
The raw materials of the embodiment of the application can be obtained by the market:
hydroxyethyl cellulose, analytically pure, molar substitution 1.8;
Sodium alginate, analytically pure;
polyethylene glycol, molecular weight 2000 analytically pure.
Preparation example
Preparation example 1
A modified hydroxyethyl cellulose is prepared by the following steps:
1.1 kg of hydroxyethyl cellulose is weighed and dispersed in 6L of isopropanol solution by ultrasonic, and is magnetically stirred for 30min in a water bath at 25 ℃ to obtain hydroxyethyl cellulose dispersion liquid;
2. Under the protection of nitrogen, preparing saturated sodium hydroxide solution by 0.05kg of sodium hydroxide solution in water, dropwise adding the saturated sodium hydroxide solution into hydroxyethyl cellulose dispersion liquid, and magnetically stirring for 24 hours to completely swell hydroxyethyl fibers to obtain mixed liquid;
3. dispersing 0.7kg of bromooctadecane in 2L of isopropanol solution to obtain bromooctadecane dispersion, dropwise adding the bromooctadecane dispersion into the mixed solution, and stirring and reacting for 5 hours at 80 ℃;
4. After the reaction is finished, the reaction system is cooled to room temperature, the product is soaked in n-hexane overnight, then suction filtration is carried out to obtain a precipitate, the precipitate is soaked in acetone solution for 3 times and suction filtration is carried out respectively, the pH value of the final product is regulated to 7 by glacial acetic acid, and then the final product is dried in vacuum for 12 hours at 45 ℃ to obtain the modified hydroxyethyl cellulose.
Preparation example 2
In the case of preparation example 2, the amount of bromooctadecane was 0.8kg, unlike in preparation example 1.
Preparation example 3
In the case of preparation example 3, the amount of bromooctadecane was 0.9kg, unlike in preparation example 1.
Preparation example 4
In the case of preparation example 4, the amount of bromooctadecane was 1kg, unlike in preparation example 1.
Examples
Examples 1 to 3
An auxiliary agent for effectively preventing hymexazol from caking, which comprises the following steps:
according to the raw material proportion in table 1, hydroxyethyl cellulose, sodium alginate, polyethylene glycol, inorganic powder and surfactant are mixed to obtain the auxiliary agent for effectively preventing hymexazol from caking.
TABLE 1 raw materials proportioning table (kg) in examples 1-3
Wherein the inorganic powder is talcum powder, the grain diameter is 0.5-1.5 mu m, and the surfactant is sodium dodecyl benzene sulfonate and ammonium stearate with the weight ratio of 2:1.
Example 4
Unlike example 2, the inorganic powder in example 4 was bentonite having a particle size of 3 to 5 μm.
Example 5
Unlike example 2, the inorganic powder in example 5 was talc to bentonite in a weight ratio of 2:4, wherein the talc particle size was 0.5-1.5 μm and the bentonite particle size was 3-5 μm.
Example 6
Unlike example 2, the inorganic powder in example 6 is talc, kaolin and bentonite in a weight ratio of 1:1:2, wherein the particle sizes of the talc, kaolin and bentonite are all 0.5-1.5 μm.
Example 7
Unlike example 5, the surfactant in example 7 was sodium dodecylbenzenesulfonate.
Example 8
Unlike example 5, the surfactant in example 8 was ammonium stearate.
Examples 9 to 12
Unlike example 5, examples 9 to 12 each replaced hydroxyethyl cellulose with an equivalent amount of modified hydroxyethyl cellulose from preparations 1 to 4.
Comparative example
Comparative example 1
Unlike example 1, comparative example 1 replaced sodium alginate with an equal amount of hydroxyethyl cellulose.
Comparative example 2
Unlike example 1, comparative example 1 replaced polyethylene glycol with an equal amount of hydroxyethylcellulose.
Comparative example 3
Unlike example 1, comparative example 3 replaced sodium alginate and polyethylene glycol with equal amounts of hydroxyethyl cellulose.
Comparative example 4
Unlike example 1, the surfactant was replaced with an equal amount of inorganic powder in comparative example 4.
Comparative example 5
Unlike example 1, the inorganic powder was replaced with an equal amount of surfactant in comparative example 5.
Comparative example 6
Unlike example 1, the surfactant and the inorganic powder were replaced with equal amounts of hydroxyethylcellulose in comparative example 6.
Performance detection
The anti-blocking agent films obtained in examples 1 to 12 and comparative examples 1 to 3 were subjected to performance test as follows, and the test results are shown in Table 2.
Dissolving an auxiliary agent for effectively preventing hymexazol from caking in water according to the weight ratio of 1:30, casting an anti-caking agent solution 20 mL on a culture dish with the diameter of 10 cm, drying in an oven with the temperature of 60 ℃, carrying out mechanical property measurement by using an mechanical universal testing machine after cooling, cutting a sample into rectangles (length of 80 mm and width of 10 mm) before testing, fixing the gauge length to be 30 mm, and ensuring the speed of a pneumatic clamp to be 5 mm/min.
TABLE 2 Performance test results
By combining examples 1-12 with comparative examples 1-6 and by combining Table 2, it can be seen that the mechanical properties of the films obtained in examples 1-12 are better than those of comparative examples 1-6, which demonstrates that the mechanical properties of the coating films obtained with the aid of the application effective in preventing the agglomeration of hymexazol are better.
It can be seen from the combination of examples 1 and comparative examples 1 to 3 and the combination of Table 2 that the mechanical properties of the coating film in example 1 are significantly better than those of the coating film obtained by using the combination of hydroxyethyl cellulose, sodium alginate and polyethylene glycol as the film forming materials to prepare the coating film, the combination of hydroxyethyl cellulose and polyethylene glycol as the film forming materials to prepare the coating film in comparative example 1, the combination of hydroxyethyl cellulose and sodium alginate as the film forming materials to prepare the coating film in comparative example 2, the combination of strong cellulose and cellulose as the film forming materials to prepare the coating film in comparative example 3, and the mechanical properties of the coating film in example 1 are significantly better than those of the coating film obtained by using the combination of hydroxyethyl cellulose, sodium alginate and polyethylene glycol as the film forming materials. This is probably because hydroxyethyl cellulose has good film forming property, hydroxyethyl cellulose is used as a main film forming substance, sodium alginate and polyethylene glycol are compounded, and the sodium alginate and the polyethylene glycol can be well crosslinked with the hydroxyethyl cellulose and uniformly dispersed, so that the film forming process is promoted, and the film forming quality and efficiency are improved.
As can be seen from the combination of examples 5 and examples 9-12 and table 2, the mechanical properties of the coating films obtained in examples 9-12 are better than those of example 5, which demonstrates that modification of hydroxyethylcellulose with long chain carbon can further improve the properties of the coating films. This is probably because grafting a long carbon chain on hydroxyethyl cellulose increases the content of ether bond and alkane structure in the polymer, improves the hydrophobic effect of the polymer, and can form nano micelle with core-shell structure in aqueous solution by self-assembly technology, so that the micelle structure formed by dispersing the polymer in water is more compact, the particle size is reduced, the self-assembly capability of the polymer is improved, and the entrapment capability of hymexazol is further improved.
Application example
Application example 1
The application of the auxiliary agent for effectively preventing the hymexazol from caking in the hymexazol comprises the following steps:
the auxiliary agent for effectively preventing the hymexazol from caking, which is obtained in the embodiment 1, is dissolved in water according to the weight ratio of 1:30 to obtain mixed solution, the mixed solution is sprayed on the surface of the hymexazol, and then the mixed solution is dried at 50 ℃, so that the auxiliary agent for effectively preventing the hymexazol from caking forms a film and is wrapped on the surface of the hymexazol.
Application examples 2 to 12
Unlike application example 1, the auxiliaries effective for preventing the agglomeration of hymexazol in application examples 2 to 12 are derived from examples 2 to 12, respectively.
Comparative application example
Comparative application examples 1 to 3
Unlike application example 1, the auxiliaries effective for preventing the agglomeration of hymexazol in comparative application examples 1 to 3 are derived from comparative examples 4 to 6, respectively.
Performance detection
The anti-blocking performance of the hymexazol obtained in the application example and the comparative application example was tested in the following manner, and the test results are shown in table 3.
Bagging and sealing the anti-caking hymexazol, then placing the hymexazol in an oven, keeping the temperature at 60 ℃ in the daytime, reducing the temperature to 25 ℃ at night, checking caking conditions on the 10 th day and the 20 th day respectively, and determining caking rate, wherein the caking rate is determined by respectively dropping the sample from the front side and the back side at the height of 1 m for 1 time, unpacking, screening by using a standard screen, weighing the total mass of the hymexazol and the mass of the hymexazol after screening, and calculating caking rate:
;
Wherein m is the mass of the caking compound fertilizer after sieving, g, and m0 is the total mass of the compound fertilizer, g.
TABLE 3 Performance test results
As can be seen from the combination of application examples 1 to 12 and comparative application examples 1 to 6 and the combination of table 3, the blocking rate of the hymexazol in application examples 1 to 12 is lower than that of comparative application examples 1 to 6, which indicates that the anti-blocking effect of the auxiliary agent for effectively preventing the hymexazol from blocking, prepared by the application, on the hymexazol is better.
As can be seen from the combination of application example 1 and comparative application examples 1 to 3, and the combination of table 3, in example 1, inorganic powder and surfactant were added to the coating film formed of hydroxyethyl cellulose, in comparative application example 1, inorganic powder was added to the coating film formed of hydroxyethyl cellulose, in comparative application example 2, surfactant was added to the coating film formed of hydroxyethyl cellulose, and in comparative application example 3, the caking rate of hymexazol in example 1 was significantly lower than in comparative application examples 1 to 3, in which the caking rate in comparative application example 3 was the highest, indicating that the addition of inorganic powder and surfactant to the coating film formed of hydroxyethyl cellulose could further improve the caking resistance of hymexazol. This is probably because the addition of the inorganic powder and the surfactant regulates the surface properties of the hydroxyethyl cellulose film, further improving the anti-caking effect of hymexazol.
It can be seen from the combination of application example 2 and application examples 4 to 6 and the combination of table 3 that the kind and the grain size grading of the inorganic powder affect the anti-caking property of the hymexazol, wherein talcum powder and bentonite are compounded in a weight ratio of 2:4, the grain size of the talcum powder is 0.5 to 1.5 mu m, and the grain size of the bentonite is 3 to 5 mu m, so that the anti-caking property is better when the compound inorganic powder is used as the inorganic powder.
As can be seen from the combination of application examples 5 and 9 to 12 and the combination of table 3, the blocking rate of hymexazol in application examples 9 to 12 is lower than that of application example 5, which indicates that the modification of hydroxyethyl cellulose can improve the anti-blocking effect of hymexazol. This is probably because the long carbon chain is grafted on the hydroxyethyl cellulose, so that the film forming quality can be regulated, the mechanical property of the film is improved, and the anti-caking effect of the film is better exerted, which can be also verified by combining the table 2.
The present embodiment is only for explanation of the present application and is not to be construed as limiting the present application, and modifications to the present embodiment, which may not creatively contribute to the present application as required by those skilled in the art after reading the present specification, are all protected by patent laws within the scope of claims of the present application.