CN109319913B - Slow-release potassium hydrogen persulfate preparation and preparation method thereof - Google Patents
Slow-release potassium hydrogen persulfate preparation and preparation method thereof Download PDFInfo
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- CN109319913B CN109319913B CN201811184568.8A CN201811184568A CN109319913B CN 109319913 B CN109319913 B CN 109319913B CN 201811184568 A CN201811184568 A CN 201811184568A CN 109319913 B CN109319913 B CN 109319913B
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- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
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- C—CHEMISTRY; METALLURGY
- C02—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F—TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE
- C02F1/00—Treatment of water, waste water, or sewage
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Abstract
The invention provides a slow-release potassium hydrogen persulfate preparation which sequentially comprises a drug-loaded pill core, an inner layer film coat and an outer layer film coat from inside to outside; the drug-loaded pellet core is characterized by comprising raw material components of potassium hydrogen persulfate, a filling agent, a plasticizer I, sodium carboxymethylcellulose and water, wherein the raw material components of the inner layer of the film coat comprise ethyl cellulose, a plasticizer II, a pore-forming agent and an organic solvent, and the raw material components of the outer layer of the film coat comprise hydroxypropyl methyl cellulose, a plasticizer III, potassium hydrogen persulfate and water. The invention also provides a preparation method of the sustained-release oxone preparation, which comprises the following steps: (1) preparing a drug-loaded pill core; (2) synthesizing an inner layer film coating solution; (3) synthesizing an outer-layer film coating solution; (4) and (4) coating. The invention can solve the problems of uncontrollable release rate, poor treatment effect, complex operation, easy moisture deterioration and high treatment cost of the existing oxone in the use process.
Description
Technical Field
The invention relates to a slow-release potassium hydrogen persulfate preparation and a preparation method thereof, belonging to the technical field of water treatment.
Background
Potassium hydrogen persulfate has super strong oxidizing property and its oxidation product has no toxicity, so that it is used widely as disinfectant, water purifier, bleaching agent and other preparation. In the domestic market at present, the potassium hydrogen persulfate is usually prepared into a potassium hydrogen persulfate compound salt preparation for disinfection, purification and other treatments of water. The potassium hydrogen persulfate compound salt preparation has unstable property, is easy to decompose when meeting water and being heated, and influences the effect, so that the storage condition requirement is high; in addition, the potassium hydrogen persulfate contained in the potassium hydrogen persulfate complex salt preparation is expensive, and in the process of using the potassium hydrogen persulfate complex salt preparation, the potassium hydrogen persulfate complex salt preparation is easy to disperse in a water body, and the reaction rate and the reaction concentration of the potassium hydrogen persulfate complex salt preparation cannot be controlled, so that the preparation has poor action effect and short action time, the preparation is often required to be artificially added to ensure that the action effect reaches the expectation, and the waste of the potassium hydrogen persulfate and the increase of the treatment cost are easily caused.
How to invent a sustained-release oxone and a preparation method thereof which can effectively control the release rate of oxone, improve the treatment effect, simplify the operation, facilitate the storage and save the cost is a problem to be solved urgently by the technical field at present.
Disclosure of Invention
The invention aims to provide a slow-release oxone preparation and a preparation method thereof, and aims to solve the problems that the release rate of oxone generated in the use process of the existing oxone preparation is uncontrollable, the treatment effect is poor, the operation is complicated, the preparation is easy to damp and deteriorate, and the treatment cost is high.
In order to achieve the purpose, the invention adopts the following technical scheme:
a sustained-release oxone preparation comprises a drug-loaded pill core, an inner layer film coat and an outer layer film coat from inside to outside in sequence; the thickness of the inner layer film coating is more than 0.1mm, and the outer layer film coating accounts for 0.1-0.5% of the total mass percent of the slow-release oxone preparation;
the drug-loaded pellet core comprises the following raw material components of potassium hydrogen persulfate, a filling agent, a plasticizer, sodium carboxymethylcellulose and water, wherein the mass ratio of the raw material components of the drug-loaded pellet core is as follows: 3-7 parts of potassium hydrogen persulfate, 14-16 parts of a filler, 3-5 parts of a first plasticizer, 0.01-0.1 part of sodium carboxymethyl cellulose, and 4-8 parts of water, wherein the first plasticizer is a water-soluble plasticizer;
the inner layer film comprises the following raw material components in percentage by mass: 12-18 parts of ethyl cellulose, 2-4 parts of a second plasticizer, 3-5 parts of a pore-foaming agent and 75-85 parts of an organic solvent, wherein the second plasticizer is a fat-soluble plasticizer;
the outer-layer film coating comprises the following raw material components in percentage by mass: 4-6 parts of hydroxypropyl methyl cellulose, 4-6 parts of a third plasticizer, 1-3 parts of potassium hydrogen persulfate and 80-120 parts of water, wherein the third plasticizer is a water-soluble plasticizer.
Further, the first plasticizer is sucrose, the second plasticizer is triethyl citrate, and the third plasticizer is polyethylene glycol-400.
Further, the pore-forming agent is polyethylene glycol-2000, the organic solvent is absolute ethyl alcohol, and the filling agent is starch.
Further, the thickness of the inner layer film coating is 0.2mm, and the outer layer film coating accounts for 0.2% of the total mass of the slow-release oxone preparation.
Further, the raw material components of the drug-loaded pellet core comprise potassium hydrogen persulfate, a filling agent, a first plasticizer, sodium carboxymethylcellulose and water, and the mass ratio of the raw material components of the drug-loaded pellet core is as follows: 6 parts of potassium hydrogen persulfate, 15 parts of a filler, 4 parts of a first plasticizer, 0.05 part of sodium carboxymethyl cellulose and 5 parts of water;
the inner layer film comprises the following raw material components in percentage by mass: ethyl cellulose 15, a second plasticizer 3, a pore-forming agent 4, an organic solvent 80;
the raw material components of the outer layer film coat comprise hydroxypropyl methyl cellulose, a third plasticizer, potassium hydrogen persulfate and water, and the mass ratio of the components of the outer layer film coat is as follows: hydroxypropyl methylcellulose 5, third plasticizer 5, potassium hydrogen persulfate 2 and water 100.
6. A preparation method of a slow-release oxone preparation comprises the following steps:
(1) preparing a drug-loaded pill core: dissolving a first plasticizer and sodium carboxymethylcellulose in water to obtain a mixed solution A, mixing potassium hydrogen persulfate and a filling agent, fully mixing with the mixed solution A, and drying to obtain a drug-loaded pill core;
(2) synthesis of inner layer film coating solution: adding ethyl cellulose into an organic solvent, heating in a water bath, stirring, adding a second plasticizer and a pore-forming agent, and stirring until the ethyl cellulose is dissolved to obtain an inner-layer film coating solution;
(3) synthesizing an outer-layer film coating solution: adding hydroxypropyl methyl cellulose and potassium hydrogen persulfate into water, heating in water bath, adding a third plasticizer, and stirring until the hydroxypropyl methyl cellulose is dissolved to obtain an outer layer film coating solution;
(4) coating a film: repeatedly soaking the medicine-carrying pellet core into the inner layer film coating solution, taking out, repeatedly soaking into the outer layer film coating solution, taking out, vibrating, filtering, and carrying out vacuum drying treatment to constant weight to obtain the sustained-release potassium hydrogen persulfate preparation.
Further, the step (2) synthesizes an inner layer film coating solution: adding ethyl cellulose into an organic solvent, heating in a water bath, adding a second plasticizer while stirring, adding a pore-forming agent after stirring for 30 minutes, stirring until the ethyl cellulose is completely dissolved, and standing for 10 minutes under the water bath heating state to obtain an inner layer film coating solution;
synthesizing an outer-layer film coating solution in the step (3): adding hydroxypropyl methylcellulose and potassium hydrogen persulfate into water, heating in water bath, adding plasticizer III, heating in water bath, stirring for 30 min at room temperature until hydroxypropyl methylcellulose is completely dissolved, and standing at room temperature for 10min to obtain outer membrane solution.
Further, the frequency of soaking the inner layer film coating solution by the medicine-carrying pill core in the step (4) is 2-6 times, and the frequency of soaking the outer layer film coating solution by the medicine-carrying pill core wrapped with the inner layer film coating in the step (4) is 2-3 times.
Further, the number of times that the medicine-carrying pill core in the step (4) soaks the inner layer film coating solution is 2, and the number of times that the medicine-carrying pill core wrapped with the inner layer film coating in the step (4) soaks the outer layer film coating solution is 2.
Further, the conditions of the water bath heating in the step (2) and the step (3) are not higher than 60 ℃, and the drying temperature in the step (1) and the step (4) is not higher than 30 ℃.
The beneficial effects of the invention are: (1) the outer layer film coat of the sustained-release oxone preparation adopts hydroxypropyl methyl cellulose, and the inner layer film coat adopts ethyl cellulose, so that after the drug-loaded pellet core is wrapped by the outer layer film coat and the inner layer film coat, the overall stability of the preparation is improved, and the sustained-release oxone preparation is prevented from deteriorating; (2) when the potassium hydrogen persulfate is wrapped by the two coatings and then placed in water, the outer layer membrane is firstly contacted with the water to be dissolved, the potassium hydrogen persulfate contained in the outer layer membrane is released, when the outer layer membrane is completely dissolved, the inner layer membrane is contacted with the water, pore channels are formed in the inner layer membrane through a pore-forming agent, the potassium hydrogen persulfate is gradually released, the purpose of slowly releasing the potassium hydrogen persulfate is achieved, and the control on the release rate of the potassium hydrogen persulfate preparation is realized; (3) the sustained-release oxone preparation can continuously play roles in disinfecting and purifying a water body and the like by controlling the release concentration of oxone within a period of time, thereby prolonging the effective reaction time of the oxone, saving the cost to the maximum extent and playing a good treatment effect; (4) in the treatment process, the preparation does not need to be put in every day on time, and the amount of the potassium hydrogen persulfate in the water can be controlled to be in a reaction equilibrium state in a long period of time, so that the operation is simplified.
Drawings
FIG. 1 is a schematic structural diagram of the present sustained-release oxone preparation;
FIG. 2 is a graph of the effect of porogen concentration on pore size of the pores of the inner membrane coating;
FIG. 3 is a graph showing the effect of porogen concentration on oxone release;
FIG. 4 is a graph of the effect of the number of layers of the inner film coat on the thickness of the inner film coat;
FIG. 5 is a graph showing the effect of the number of inner film coats on the amount of oxone released;
FIG. 6 is a graph showing the test of the thermal stability of the present sustained-release oxone preparation.
Wherein: a drug-loaded pellet core 1; an inner layer film coat 2; and an outer film coating 3.
Detailed Description
The technical solutions of the present invention will be described in detail below in order to clearly understand the technical features, objects, and advantages of the present invention, but the present invention is not limited to the practical scope of the present invention.
The invention analyzes the following experimental results of influencing factors to determine the component proportion and the preparation conditions of the buffer type potassium hydrogen persulfate preparation.
First, the influence of the pore-forming agent concentration on the size of the pore diameter of the fat-soluble membrane
The pore-forming agent selects polyethylene glycol-2000, the concentration of the polyethylene glycol-2000 is taken as a univariate factor, five concentration groups of 1g/100mL, 2g/100mL, 3g/100mL, 4g/100mL and 5g/100mL are set, and the mass of the rest raw material components of the inner layer membrane coat 2 is constant as follows: 15g of ethyl cellulose, 3g of triethyl citrate and 100mL (80g) of absolute ethanol. The inner film coat 2 synthesized by the polyethylene glycol-2000 with different concentration groups is directly observed by an electron microscope, and the result is shown in fig. 2, as the concentration of the polyethylene glycol-2000 is increased, the pore diameter of micropores in the inner film coat 2 is increased, and the higher the concentration of the polyethylene glycol-2000 is, the higher the rate of the pore diameter increase is.
Secondly, influence of pore-forming agent concentration on release amount of potassium hydrogen persulfate
The pore-forming agent selects polyethylene glycol-2000, the concentration of the polyethylene glycol-2000 is taken as a univariate factor, five concentration groups of 1g/100mL, 2g/100mL, 3g/100mL, 4g/100mL and 5g/100mL are set, and the mass of the rest raw material components of the inner layer membrane coat 2 is constant as follows: 15g of ethyl cellulose, 3g of triethyl citrate and 100mL (80g) of absolute ethanol. After the inner membrane coating 2 synthesized by the polyethylene glycol-2000 with different concentration groups is prepared into a slow-release oxone preparation, the slow-release oxone preparation is put into water for testing, and the result is shown in fig. 3, as the release amount of oxone is larger and larger along with the time, the higher the porogen concentration is, the more the release amount of oxone is in the same time, and the faster the release rate of oxone is. When the concentration of the polyethylene glycol-2000 reaches 5g/100mL, the prepared sustained-release oxone preparation can be disintegrated in water within 10 hours.
Influence of thickness of inner layer film coating on release amount of potassium hydrogen persulfate
The thickness of the inner layer film coat 2 is used as a univariate factor, the number of layers of the inner layer film coat 2 wrapping the drug-loaded pill core 1 is controlled by controlling the frequency of soaking the drug-loaded pill core 1 in the inner layer film coat solution, the thickness of the inner layer film coat 2 is further adjusted, and the number of layers of the inner layer film coat 2 wrapping the drug-loaded pill core 1 is set to be 1-6. The inner layer film coat 2 comprises the following raw material components in parts by mass: 15g of ethyl cellulose, 3g of triethyl citrate, 20004 g of polyethylene glycol and 100mL (80g) of absolute ethyl alcohol. Wrapping the prepared drug-loaded pellet core 1 according to the number of the inner layer film coatings 2, finally preparing a slow-release type potassium hydrogen persulfate preparation, and putting the prepared drug-loaded pellet core into water for testing, wherein the results are shown in figures 4 and 5, and the thickness of the inner layer film coatings 2 wrapped on the surface of the drug-loaded pellet core 1 is about 0.10mm each time the drug-loaded pellet core is soaked; the slow-release oxone preparation with the number of the inner layer film coat 2 being only 1 layer is disintegrated in water within 10 hours; the release amount of the potassium hydrogen persulfate is increased along with the time, the thickness of the inner layer membrane coating 2 of the sustained-release potassium hydrogen persulfate preparation is thicker as the number of the layers is larger, and the release amount of the potassium hydrogen persulfate in the same time is smaller and the release rate of the potassium hydrogen persulfate is slower.
Thermal stability of the sustained-release oxone preparation
The slow-release potassium hydrogen persulfate preparation is put into an oven, is respectively placed for 4 hours at 20 ℃, 30 ℃, 40 ℃, 50 ℃ and 60 ℃, and then is put into water for 10 hours, and the release degree of sulfate ions is observed. As shown in FIG. 6, potassium hydrogen persulfate was not decomposed at about 20 ℃ to 30 ℃ and slowly decomposed at 40 ℃ and slowly decomposed at 60 ℃ to almost completely decompose it.
Method for detecting release amount of potassium hydrogen persulfate and release amount of potassium hydrogen persulfate respectively
Because potassium hydrogen persulfate can be decomposed into potassium sulfate and potassium hydrogen sulfate at the temperature of more than 30 ℃, the released potassium hydrogen persulfate is designed to be heated and boiled for a period of time, and a proper amount of sodium hydroxide is added to completely decompose and convert the potassium hydrogen persulfate into sulfate ions, and then the amount of the sulfate ions is measured according to a gravimetric method described in the fourth edition of the State environmental protection administration of Water and wastewater monitoring and analysis method to determine the amount of the sulfate ions. And finally, calculating the mass of the released potassium hydrogen persulfate respectively by converting sulfur atoms in the barium persulfate and the potassium hydrogen persulfate.
The effect test of the slow-release type potassium hydrogen persulfate preparation comprises the following steps:
first, sterilization capability test
Example 1
(1) The slow-release type potassium hydrogen persulfate preparation comprises the following components in percentage by weight: the medicine-carrying pill core 1 comprises the following raw material components in percentage by mass: 0.5 of potassium hydrogen persulfate, 15 of starch, 4 of cane sugar, 0.05 of sodium carboxymethyl cellulose and 5 of water; the inner layer film coat 2 comprises the following raw material components in percentage by mass: ethyl cellulose 15, triethyl citrate 3, polyethylene glycol-20004, absolute ethyl alcohol 80; the outer layer film coating 3 comprises the following raw material components in percentage by mass: hydroxypropyl methylcellulose 5, polyethylene glycol-4005, potassium hydrogen persulfate 2 and water 100.
(2) Preparing a slow-release oxone preparation:
firstly, preparing a drug-loaded pill core 1: dissolving sucrose and sodium carboxymethylcellulose in water to obtain a mixed solution A, mixing potassium hydrogen persulfate and starch, mixing with the mixed solution A fully, and drying to obtain a drug-loaded pellet core 1;
synthesizing an inner layer film coating solution: adding ethyl cellulose into absolute ethyl alcohol, heating in a water bath, stirring, adding triethyl citrate and polyethylene glycol-2000, and stirring until the ethyl cellulose is dissolved to obtain an inner-layer film coating solution;
thirdly, synthesizing an outer layer film coating solution: adding hydroxypropyl methyl cellulose and potassium hydrogen persulfate into water, heating in water bath, adding polyethylene glycol-400, stirring until the hydroxypropyl methyl cellulose is dissolved to obtain outer membrane coating solution;
fourthly, coating: repeatedly soaking the drug-loaded pellet core 1 into the inner layer film coating solution, taking out, repeatedly soaking into the outer layer film coating solution, taking out, vibrating, filtering, and carrying out vacuum drying treatment to constant weight to obtain the sustained-release potassium hydrogen persulfate preparation.
Example 2
The formulation ingredients and proportions, specific preparation steps, were repeated as in example 1, except that: the mass ratio of the potassium hydrogen persulfate of the drug-loaded pill core 1 is 1.
Example 3
The ingredients and proportions of the preparation, the specific preparation steps, are repeated as in example 1, except that: the mass ratio of the potassium hydrogen persulfate of the medicine-carrying pellet core 1 is 1.5.
Example 4
The formulation ingredients and proportions, specific preparation steps, were repeated as in example 1, except that: the mass ratio of the potassium hydrogen persulfate of the drug-loaded pill core 1 is 3.
Example 5
The ingredients and proportions of the preparation, the specific preparation steps, are repeated as in example 1, except that: the mass ratio of the potassium hydrogen persulfate of the drug-loaded pill core 1 is 6.
5 sustained-release oxone formulations of examples 1-5 above were prepared and subjected to the following bactericidal activity test:
(1) preparing a bacterial suspension: staphylococcus aureus, Escherichia coli and hemolytic streptococcus are selected as test bacteria. Taking each freeze-dried strain, performing enrichment culture, separation and purification, selecting a typical single colony, inoculating the single colony into a common broth culture medium, culturing at 37 ℃ for 24 hours, and diluting with physiological saline containing 1g/L tryptone to obtain test bacterial suspension.
(2) And (3) sterilization test: the test was carried out at room temperature (20 ℃ C. -25 ℃ C.). 100mL of the bacterial suspension was mixed with 900mL of sterile water to form 1L of test solution. The 5 sustained-release oxones were added to the 1L test solution and allowed to act for 10 minutes. Taking 1.0mL of the reacted test solution, adding into a test tube containing 9.0mL of a neutralizer, uniformly mixing, and neutralizing for 10 min. After fully and uniformly mixing, inoculating a sampling solution, counting and culturing viable bacteria, and calculating a killing logarithm value. The experiment was repeated 3 times to find the average kill log.
(3) As a result: see table 1. The 5 slow-release potassium hydrogen persulfate preparations have obvious bactericidal effect on escherichia coli, staphylococcus aureus and hemolytic streptococcus, and the effective concentration of the potassium hydrogen persulfate is in the concentration range of 3-6 g/L, so that the bactericidal effect is better.
TABLE 1 average log kill
| Test strains | Test number | Content of active ingredient (mg/L) | Mean kill log |
| Escherichia coli | Example 1 | 500 | 4.02 |
| Escherichia coli | Example 2 | 1000 | 5.08 |
| Escherichia coli | Example 3 | 1500 | 5.79 |
| Escherichia coli | Example 4 | 3000 | 6.34 |
| Escherichia coli | Example 5 | 6000 | 6.69 |
| Staphylococcus aureus (Staphylococcus aureus) | Example 1 | 500 | 4.09 |
| Staphylococcus aureus | Example 2 | 1000 | 5.16 |
| Staphylococcus aureus | Example 3 | 1500 | 5.87 |
| Staphylococcus aureus | Example 4 | 3000 | 6.47 |
| Staphylococcus aureus | Example 5 | 6000 | 6.79 |
| Hemolytic streptococcus | Example 1 | 500 | 4.14 |
| Hemolytic streptococcus | Example 2 | 1000 | 5.21 |
| Hemolytic streptococcus | Example 3 | 1500 | 5.92 |
| Hemolytic streptococcus | Example 4 | 3000 | 6.51 |
| Hemolytic streptococcus | Example 5 | 6000 | 6.98 |
Second, test of the amount of oxone released from the sustained-release oxone
The sustained-release oxone prepared in example 5 was placed in a reaction vessel of an intelligent dissolution apparatus containing 1L of water, and the dissolution rate of the preparation was tested. 5ml of the dissolution liquid is taken out at intervals of corresponding time, the concentration of the dissolution liquid is measured, and the corresponding solvent is supplemented in time. The test was repeated 4 times at each time point until the dissolution test was completed at all time points, and finally the dissolution was converted to the released amount of oxone. The results are shown in table 2, and the differences of the results of 4 parallels measured at each time point are not large, which indicates that the sustained-release performance of the preparation is stable, and the preparation continuously releases oxone along with the advance of time, thereby realizing the effective sustained release of oxone.
TABLE 2 Release of oxone
Third, testing the sewage purifying ability of the slow-release type potassium hydrogen persulfate preparation
The slow-release oxone prepared in example 5 was placed in a beaker containing 500mL of wastewater, after 10 minutes the turbidity of the solution was significantly reduced, and 500mL of wastewater was added to the vessel every subsequent 30 minutes and observed for the turbidity in the subsequent 10 minutes until the wastewater treatment capacity reached 2000mL, and the experiment was stopped. In this experiment, the turbidity decreased significantly 10 minutes after each addition of the wastewater as compared to the immediately preceding addition. Thus, the preparation can maintain the sewage purification capability for a long time.
The invention provides a slow-release potassium hydrogen persulfate preparation which comprises a medicine-carrying pill core 1, an inner layer membrane coating 2 and an outer layer membrane coating 3 from inside to outside in sequence as shown in figure 1; the thickness of the inner layer film coat 2 is more than 0.1mm, and the outer layer film coat 3 accounts for 0.1-0.5 percent of the total mass percent of the slow-release type potassium hydrogen persulfate preparation;
the drug-loaded pellet core 1 comprises the following raw material components of potassium hydrogen persulfate, a filling agent, a first plasticizer, sodium carboxymethylcellulose and water, wherein the mass ratio of the raw material components of the drug-loaded pellet core 1 is as follows: 3-7 parts of potassium hydrogen persulfate, 14-16 parts of a filler, 3-5 parts of a first plasticizer, 0.01-0.1 part of sodium carboxymethyl cellulose, 4-8 parts of water, and the first plasticizer is a water-soluble plasticizer;
the raw material components of the inner layer membrane coat 2 comprise ethyl cellulose, a second plasticizer, a pore-forming agent and an organic solvent, and the mass ratio of the raw material components of the inner layer membrane coat 2 is as follows: 12-18 parts of ethyl cellulose, 2-4 parts of a second plasticizer, 3-5 parts of a pore-foaming agent, 75-85 parts of an organic solvent, wherein the second plasticizer is a fat-soluble plasticizer;
the raw material components of the outer layer film coat 3 comprise hydroxypropyl methyl cellulose, a third plasticizer, potassium hydrogen persulfate and water, and the mass ratio of the raw material components of the outer layer film coat 3 is as follows: 4-6 parts of hydroxypropyl methyl cellulose, 4-6 parts of a third plasticizer, 1-3 parts of potassium hydrogen persulfate, 80-120 parts of water, and the third plasticizer is a water-soluble plasticizer.
The invention prepares the potassium hydrogen persulfate into the drug-loaded pill core 1 to wrap two different coatings so as to achieve the purpose of slow release. The inner layer membrane 2 takes ethyl cellulose as a slow release material, and is added with a second plasticizer, a pore-forming agent and an organic solvent to prepare a fat-soluble coating with a certain pore canal; the outer layer film coating 3 is a water-soluble coating containing potassium hydrogen persulfate, which is prepared by taking hydroxypropyl methyl cellulose as a slow release material and adding a third plasticizer, potassium hydrogen persulfate and water.
The thickness of the inner layer film coat 2 is too thin, the inner layer film coat 2 can be disintegrated and broken in a short time, and the slow release action time is too short, so that the thickness of the inner layer film coat 2 is more than 0.1mm, and the potassium hydrogen persulfate can be slowly released and the slow release time can be prolonged; the outer layer film coat 3 only accounts for 0.1-0.5 percent of the total mass percent of the slow-release oxone preparation, the thickness of the outer layer film coat is very thin, the slow-release oxone preparation can play a role in maintaining the stability of the preparation before being thrown into a water body, and the slow-release oxone preparation can be dissolved in a short time after being thrown into the water body, so that the inner layer film coat 2 is exposed, and the slow release of effective components is realized.
Ethyl cellulose is fat-soluble, and has functions of film forming, binding, filling, etc. Because the ethyl cellulose can be dissolved in the absolute ethyl alcohol, volatile and highly toxic solvents are not needed, and the secondary pollution of the residual toxic solvents to the water body is avoided. The slow-release drug-loaded pellet core is insoluble in water, stable in property, not easy to deteriorate, good in cold resistance, salt resistance and moisture absorption resistance, and the preparation wrapped by the slow-release drug-loaded pellet core does not need to worry about the problem of deterioration and the problem of easy deterioration of potassium hydrogen persulfate in the drug-loaded pellet core 1, so that the slow-release drug-loaded pellet core can be used as a slow-release material and can protect the drug-loaded pellet core 1, and the slow-release drug-loaded pellet core can be used for two purposes at a stroke.
Hydroxypropyl methylcellulose is water-soluble, readily dispersible in hot water but not directly soluble in hot water, and slowly swells in cold water. Because the water-soluble polyurethane has better thickening capacity, stability, film-forming property and water-retaining property, the water-soluble polyurethane is soluble in water under specific conditions, and the stability of a preparation coated by the water-soluble polyurethane is improved well, so that the preparation is easy to store.
Hydroxypropyl methyl cellulose is selected as the outer layer film coat 3, ethyl cellulose is selected as the inner layer film coat 2, so that the overall stability of the preparation is improved after the drug-loaded pill core 1 is wrapped by the outer layer film coat 3 and the inner layer film coat 2, and the problem that the conventional potassium hydrogen persulfate preparation is easy to deteriorate is solved.
When the potassium hydrogen persulfate is wrapped by the two coatings and then is placed in water, the outer layer membrane 3 is firstly contacted with the water, and the outer layer membrane 3 is dissolved when the water is dissolved due to the water solubility of the outer layer membrane 3, so that the potassium hydrogen persulfate contained in the outer layer membrane 3 is released, and the effects of disinfection, purification and the like on the water body can be realized. After the outer layer membrane coating 3 is completely dissolved, the inner layer membrane coating 2 is contacted with water, because the ethyl cellulose of the inner layer membrane coating 2 is a fat-soluble material and is insoluble when meeting water, and the pore-forming agent in the inner layer membrane coating 2 is a water-soluble material and is dissolved when meeting water, a pore channel can be formed in the inner layer membrane coating 2, and the potassium hydrogen persulfate in the drug-carrying pellet core 1 gradually releases the potassium hydrogen persulfate through the pore channel of the inner layer membrane coating 2, so that the purpose of slowly releasing the potassium hydrogen persulfate is achieved. On the basis of the material selection of the sustained-release oxone preparation, the release rate of oxone can be effectively controlled by adjusting the content of core oxone, the concentration of pore-forming agent, the thickness of the inner layer membrane 2, the percentage of the outer layer membrane 3 in the total mass and the content of oxone in the outer layer membrane 3. Thereby solving the problem that the prior potassium hydrogen persulfate preparation can not control the action concentration and the action time.
The slow-release oxone preparation can control the release rate of oxone and the release concentration of oxone to continuously play roles in disinfecting and purifying water bodies within a period of time, so that the effective reaction time of oxone is prolonged, the cost can be saved to the maximum extent, and a good treatment effect can be achieved; in the treatment process, the amount of the potassium hydrogen persulfate in the water can be controlled to be in a reaction balance state within a long period of time without putting the preparation on time every day, and the problems of complex operation, poor treatment effect and high treatment cost of the conventional preparation are solved.
As the mass ratio of the pore-forming agent in the inner membrane 2 is increased within a certain range, the pore diameter of the pore channel of the inner membrane 2 is increased, the number of the pore channels is increased, the release amount of the potassium hydrogen persulfate in the same time is increased, and the release rate of the whole potassium hydrogen persulfate is increased; when the mass ratio of the pore-forming agent in the inner layer film coat 2 exceeds a certain range, the pore-forming agent is excessive, and the inner layer film coat 2 is easy to disintegrate and break. When the mass ratio of the pore-forming agent in the inner layer membrane 2 is more than 3, the diameter of the pore channel formed in the inner layer membrane 2 is obviously increased, and the release rate of the potassium hydrogen persulfate is obviously accelerated; when the mass ratio of the pore-forming agent in the inner layer of the membrane coating 2 is more than 5, the inner layer of the membrane coating 2 is disintegrated and broken within 10 hours, so that the mass ratio of the pore-forming agent in the inner layer of the membrane coating 2 is selected to be 3-5.
Preferably, the first plasticizer is sucrose, the second plasticizer is triethyl citrate, and the third plasticizer is polyethylene glycol-400.
The sucrose is a low-volatility compound, has good water solubility, is used as a plasticizer of the drug-loaded pill core 1, is dissolved into a sucrose solution by water, and is fully contacted and mixed with the main component of the drug-loaded pill core 1, so that the overall mechanical property and the permeability of the drug-loaded pill core 1 can be improved.
The triethyl citrate has fat solubility, good mildew resistance and oil resistance, low toxicity and no harm to the environment, is used as a plasticizer of the inner layer film coat 2 to improve the flexibility of the inner layer film coat 2, can assist the ethyl cellulose to form a more stable coat, and ensures the slow release performance of the inner layer film coat 2.
The polyethylene glycol-400 has water solubility and non-volatility, has low toxicity and is harmless to the environment, and as a plasticizer of the outer film coating 3, the polyethylene glycol-400 can properly improve the mechanical property of the outer film coating 3, effectively assist hydroxypropyl methyl cellulose to form a stable coating, ensure that the drug-loaded pill core 1 is not easily interfered by water vapor, and improve the overall stability of the preparation.
Preferably, the pore-forming agent is polyethylene glycol-2000, the organic solvent is absolute ethyl alcohol, and the filling agent is starch.
The fat-soluble inner layer membrane coat 2 contains water-soluble pore-forming agent particles, when the drug-carrying pellet core 1 is coated by the inner layer membrane coat 2 and then is contacted with water, the inner layer membrane coat 2 is insoluble in water, and the pore-forming agent can be dissolved in the water to leave a small hole, so that the potassium hydrogen persulfate of the drug-carrying pellet core 1 is gradually released into the water through the pore channel. The water-soluble pore-forming agent is preferably polyethylene glycol-2000 which can form tiny pores, is easy to disperse uniformly in solid particles and forms a certain pore channel with ethyl cellulose through stirring, is easy to dissolve in water, is insoluble in an organic solvent, has good effect and is low in price.
The organic solvent is used for dissolving fat-soluble ethyl cellulose, and in order to ensure that the preparation is safer to use and avoid secondary pollution to water, non-toxic absolute ethyl alcohol is preferably used as the organic solvent to promote the ethyl cellulose to be dissolved to prepare the inner layer film coat 2.
The filler is a main body material of the drug-loaded pill core 1 except for potassium hydrogen persulfate, is a framework material for supporting the drug-loaded pill core 1, is preferably starch, is an easily available material, is low in price and is a high-quality harmless filler. With starch and potassium peroxydisulfate granule mixing, potassium peroxydisulfate distributes around starch, when medicine carrying pellet core 1 contacts with water through the pore of inner layer membrane coating 2, starch dissolves in aqueous gradually, exposes potassium peroxydisulfate granule gradually simultaneously, and the potassium peroxydisulfate granule meets water and dissolves, plays the effect efficiency of this preparation.
Preferably, the thickness of the inner layer film coating 2 is 0.2mm, and the outer layer film coating 3 accounts for 0.2 percent of the total mass of the slow-release type potassium hydrogen persulfate preparation.
The higher the thickness of the inner layer film coat 2, the less oxone is released in the same period of time, and the slower the rate of oxone release. When the thickness of the inner layer film coat 2 of the preparation is less than 0.2mm, the thickness is too thin, and the inner layer film coat 2 is disintegrated and broken within 10 hours; when the thickness of the inner film coat 2 of the preparation is 0.2mm, the preparation is not disintegrated after being acted for 50 hours, and the release amount of the potassium hydrogen persulfate is larger than that of the inner film coat 2 with other thicknesses.
Preferably, the raw material components of the drug-loaded pellet core 1 comprise potassium hydrogen persulfate, a filling agent, a first plasticizer, sodium carboxymethylcellulose and water, and the mass ratio of the raw material components of the drug-loaded pellet core 1 is as follows: 6 parts of potassium hydrogen persulfate, 15 parts of a filler, 4 parts of a first plasticizer, 0.05 part of sodium carboxymethyl cellulose and 5 parts of water;
the raw material components of the inner layer membrane coat 2 comprise ethyl cellulose, a second plasticizer, a pore-forming agent and an organic solvent, and the mass ratio of the raw material components of the inner layer membrane coat 2 is as follows: ethyl cellulose 15, a second plasticizer 3, a pore-forming agent 4, an organic solvent 80;
the raw material components of the outer layer film coat 3 comprise hydroxypropyl methyl cellulose, a third plasticizer, potassium hydrogen persulfate and water, and the mass ratio of each component of the outer layer film coat 3 is as follows: hydroxypropyl methylcellulose 5, third plasticizer 5, potassium hydrogen persulfate 2 and water 100.
As the mass ratio of the pore-forming agent in the inner membrane 2 is increased within a certain range, the pore diameter of the pore channel of the inner membrane 2 is increased, the number of the pore channels is increased, the release amount of the potassium hydrogen persulfate in the same time is increased, and the release rate of the whole potassium hydrogen persulfate is increased. When the mass ratio of the pore-forming agent in the inner layer film coat 2 is 4, the release amount of the potassium hydrogen persulfate is the largest on the premise of not disintegrating after 50 hours of action.
The invention also provides a preparation method of the slow-release oxone preparation, which comprises the following steps:
(1) preparing a drug-loaded pill core 1: dissolving a first plasticizer and sodium carboxymethylcellulose in water to obtain a mixed solution A, mixing potassium hydrogen persulfate and a filling agent, fully mixing with the mixed solution A, and drying to obtain a drug-loaded pellet core 1;
(2) synthesis of inner layer film coating solution: adding ethyl cellulose into an organic solvent, heating in a water bath, stirring, adding a second plasticizer and a pore-forming agent, and stirring until the ethyl cellulose is dissolved to obtain an inner-layer film coating solution;
(3) synthesizing an outer-layer film coating solution: adding hydroxypropyl methyl cellulose and potassium hydrogen persulfate into water, heating in water bath, adding a third plasticizer, and stirring until the hydroxypropyl methyl cellulose is dissolved to obtain an outer-layer film coating solution;
(4) coating a film: repeatedly soaking the drug-loaded pellet core 1 into the inner layer film coating solution, taking out, repeatedly soaking into the outer layer film coating solution, taking out, vibrating, filtering, and carrying out vacuum drying treatment to constant weight to obtain the sustained-release potassium hydrogen persulfate preparation.
Potassium hydrogen persulfate in the drug-loaded pellet core 1 is mixed with the filler, and the filler is used as a skeleton structure of the drug-loaded pellet core 1, so that potassium hydrogen persulfate particles are distributed around the filler and gradually release potassium hydrogen persulfate when meeting water; and the plasticizer I, the sodium carboxymethylcellulose and the water are mixed, so that the mechanical strength of the drug-loaded pill core 1 is enhanced, and the shaping is easy.
The slow release material ethylcellulose and the second plasticizer in the inner layer membrane coat 2 are fat-soluble substances, organic solvent is required to be used for dissolving, heating and stirring are required in the dissolving process, the ethylcellulose is promoted to be fully dissolved, the pore-foaming agent added later is water-soluble substances and insoluble in the organic solvent, the original solid particle form of the pore-foaming agent is reserved and distributed in liquid, and the ethylcellulose which is difficult to dissolve is fully dissolved.
The hydroxypropyl methyl cellulose which is a slow-release material in the outer film coat 3 is a water-soluble substance and can be dissolved in water under the condition of heating and stirring; a third plasticizer which is soluble in water is added to increase the overall mechanical strength of the outer-layer film coat 3, so that the shaping is easy; adding a proper amount of potassium hydrogen persulfate to provide an initial release amount before the medicine-carrying pellet core 1 is contacted with water, stabilizing the effect efficacy of the preparation at the initial stage, and fully dissolving the hydroxypropyl methylcellulose which is difficult to dissolve.
According to the steps, the drug-loaded pill core 1, the inner layer membrane coating solution and the outer layer membrane coating solution are obtained, the drug-loaded pill core 1 is repeatedly soaked into the inner layer membrane coating solution, the thickness of the inner layer membrane coating 2 is adjusted by controlling the soaking times of the drug-loaded pill core 1, the inner layer membrane coating 2 is wrapped on the drug-loaded pill core 1, the drug-loaded pill core is repeatedly soaked into the outer layer membrane coating solution, the percentage of the outer layer membrane coating 3 to the total mass of the slow-release potassium hydrogen persulfate preparation is adjusted by controlling the soaking times of the drug-loaded pill core, then the redundant solution on the outer surface of the outer layer membrane coating 3 is removed by shaking and filtering, and the problem that the preparation is deteriorated due to high moisture is solved.
Preferably, the step (2) synthesizes an inner layer film coating solution: adding ethyl cellulose into an organic solvent, heating in a water bath, adding a second plasticizer while stirring, adding a pore-forming agent after stirring for 30 minutes, stirring until the ethyl cellulose is completely dissolved, and standing for 10 minutes under the water bath heating state to obtain an inner layer film coating solution;
synthesizing an outer-layer film coating solution: adding hydroxypropyl methylcellulose and potassium hydrogen persulfate into water, heating in water bath, adding plasticizer III, heating in water bath, stirring for 30 min at room temperature until hydroxypropyl methylcellulose is completely dissolved, and standing at room temperature for 10min to obtain outer membrane solution.
Through repeated experiments, the ethyl cellulose is easy to be fully dissolved after being continuously stirred for 30 minutes in warm water; the hydroxypropyl methyl cellulose is stirred continuously for 30 minutes in warm water, and then is easy to be fully dissolved under the condition of continuously stirring after being cooled to room temperature. The ethyl cellulose and the hydroxypropyl methyl cellulose can generate bubbles in the process of continuously stirring and dissolving, and the quality of the synthesized inner film coat 2 and the synthesized outer film coat 3 can be influenced by the existence of the bubbles, so that after the ethyl cellulose and the hydroxypropyl methyl cellulose are fully dissolved, the mixture is kept stand for 10 minutes under the original temperature condition, the bubbles are naturally discharged, and the quality of the synthesized inner film coat 2 and the synthesized outer film coat 3 is improved.
Preferably, the frequency of soaking the inner layer film coating solution in the medicine carrying pill core 1 in the step (4) is 2-6 times, and the frequency of soaking the outer layer film coating solution in the medicine carrying pill core 1 wrapped with the inner layer film coating 2 in the step (4) is 2-3 times.
The drug-loaded pill core 1 is repeatedly soaked into the inner-layer film coating solution, the thickness of the inner-layer film coating 2 is adjusted by controlling the soaking times of the drug-loaded pill core 1, then the drug-loaded pill core 1 wrapped with the inner-layer film coating 2 is repeatedly soaked into the outer-layer film coating solution, and the percentage of the outer-layer film coating 3 in the total mass of the slow-release type potassium hydrogen persulfate preparation is adjusted by controlling the soaking times.
According to measurement, the inner layer film coat solution is soaked once in the medicine-carrying pill core 1, the thickness of the added inner layer film coat 2 is 0.10mm, and the inner layer film coat 2 with the thickness of 0.2-0.60 mm is obtained after soaking for 2-6 times; when the thickness of the inner layer film coat 2 is less than 0.2mm, the thickness is too thin, and the inner layer film coat 2 is disintegrated and broken in no more than 10 hours; when the thickness of the inner layer film coat 2 is more than 0.60mm, the thickness is too thick, the release of the potassium hydrogen persulfate is too slow, and the efficacy is obviously weakened, so that the drug-loaded pill core 1 is preferably soaked into the inner layer film coat solution for 2-6 times.
Through measurement, the drug-loaded pellet core 1 wrapped with the inner layer membrane coating 2 is soaked in the outer layer membrane coating solution for 2-3 times, the outer layer membrane coating 3 accounts for 0.2-0.3% of the total mass percent of the slow-release oxone preparation, the thickness of the slow-release oxone preparation is very thin, the slow-release oxone preparation can play a role in maintaining the stability of the preparation before being thrown into a water body, the slow-release oxone preparation can be dissolved in a short time after being thrown into the water body, the inner layer membrane coating 2 is exposed, and the slow release of effective components is realized.
Preferably, the frequency of soaking the inner layer film coating solution in the pellet core 1 coated with the inner layer film coating 2 in the step (4) is 2 times, and the frequency of soaking the outer layer film coating solution in the pellet core 1 coated with the inner layer film coating 2 in the step (4) is 2 times.
The frequency of soaking the inner layer film coating solution in the drug-loaded pellet core 1 is 2 times, the thickness of the obtained inner layer film coating 2 is 0.2mm, the inner layer film coating does not disintegrate after 50 hours of action, and the release amount of potassium hydrogen persulfate is larger than that of the inner layer film coating 2 with other thicknesses. The drug-loaded pill core 1 wrapped with the inner layer film coat 2 is soaked in the outer layer film coat solution for 2 times, the obtained outer layer film coat 3 accounts for 0.2 percent of the total mass percent of the slow-release type potassium hydrogen persulfate preparation, the thickness of the preparation is very thin, and the stability and the slow-release effect of the preparation can be simultaneously considered.
Preferably, the conditions of the water bath heating in the step (2) and the step (3) are not higher than 60 ℃, and the drying temperature in the step (1) and the step (4) is not higher than 30 ℃.
The ethyl cellulose and the hydroxypropyl methyl cellulose can only be dispersed in hot water with the temperature of higher than 60 ℃, but the dissolution performance is poor, the full dissolution of the ethyl cellulose and the hydroxypropyl methyl cellulose is influenced, and the heating condition of a water bath is not higher than 60 ℃. Potassium hydrogen persulfate can be decomposed into potassium sulfate and potassium hydrogen sulfate at the temperature of more than 30 ℃, potassium hydrogen persulfate is not decomposed at the temperature of about 20-30 ℃, the potassium hydrogen persulfate starts to be slowly decomposed at the temperature of 40 ℃, the decomposition is slowed down at the temperature of 60 ℃ and is close to complete decomposition, so the drying temperature of the slow-release potassium hydrogen persulfate preparation is not higher than 30 ℃.
The technical principle of the present invention is described above in connection with specific embodiments. The description is made for the purpose of illustrating the principles of the invention and should not be construed in any way as limiting the scope of the invention. Based on the explanations herein, those skilled in the art will be able to conceive of other embodiments of the present invention without inventive effort, which would fall within the scope of the present invention.
Claims (8)
1. The application of a drug-loaded structure in preparing a sustained-release oxone preparation is characterized in that the drug-loaded structure sequentially comprises a drug-loaded pill core, an inner layer membrane coat and an outer layer membrane coat from inside to outside; the thickness of the inner layer film coating is more than 0.1mm, and the outer layer film coating accounts for 0.1-0.5% of the total mass percent of the slow-release oxone preparation;
the drug-loaded pellet core comprises the following raw material components of potassium hydrogen persulfate, a filling agent, a plasticizer, sodium carboxymethylcellulose and water, wherein the mass ratio of the raw material components of the drug-loaded pellet core is as follows: 3-7 parts of potassium hydrogen persulfate, 14-16 parts of a filler, 3-5 parts of a first plasticizer, 0.01-0.1 part of sodium carboxymethyl cellulose, and 4-8 parts of water, wherein the first plasticizer is a water-soluble plasticizer;
the inner layer film comprises the following raw material components in percentage by mass: 12-18 parts of ethyl cellulose, 2-4 parts of a second plasticizer, 3-5 parts of a pore-foaming agent and 75-85 parts of an organic solvent, wherein the second plasticizer is a fat-soluble plasticizer;
the raw material components of the outer layer film coating comprise hydroxypropyl methyl cellulose, a third plasticizer, potassium hydrogen persulfate and water, and the mass ratio of the raw material components of the outer layer film coating is as follows: 4-6 parts of hydroxypropyl methyl cellulose, 4-6 parts of a third plasticizer, 1-3 parts of potassium hydrogen persulfate, and 80-120 parts of water, wherein the third plasticizer is a water-soluble plasticizer;
the preparation method of the sustained-release oxone is characterized by comprising the following steps:
(1) preparing a drug-loaded pill core: dissolving a first plasticizer and sodium carboxymethylcellulose in water to obtain a mixed solution A, mixing potassium hydrogen persulfate and a filling agent, fully mixing with the mixed solution A, and drying to obtain a drug-loaded pill core;
(2) synthesis of inner layer film coating solution: adding ethyl cellulose into an organic solvent, heating in a water bath, stirring, adding a second plasticizer and a pore-forming agent, and stirring until the ethyl cellulose is dissolved to obtain an inner-layer film coating solution;
(3) synthesizing an outer-layer film coating solution: adding hydroxypropyl methyl cellulose and potassium hydrogen persulfate into water, heating in water bath, adding a third plasticizer, and stirring until the hydroxypropyl methyl cellulose is dissolved to obtain an outer-layer film coating solution;
(4) coating a film: repeatedly soaking the drug-loaded pill core into the inner layer film coating solution, taking out, repeatedly soaking into the outer layer film coating solution, taking out, vibrating, filtering, and performing vacuum drying treatment to constant weight to obtain the sustained-release potassium hydrogen persulfate preparation;
the conditions of water bath heating in the step (2) and the step (3) are not higher than 60 ℃, and the drying temperature in the step (1) and the step (4) is not higher than 30 ℃.
2. The use of a drug-loaded structure in the preparation of a sustained release oxone formulation according to claim 1, wherein the plasticizer No. one is sucrose, the plasticizer No. two is triethyl citrate and the plasticizer No. three is polyethylene glycol-400.
3. The use of the drug-loaded structure in the preparation of the sustained-release oxone preparation according to claim 1, wherein the pore-forming agent is polyethylene glycol-2000, the organic solvent is absolute ethanol, and the filler is starch.
4. The use of the drug-loaded structure in the preparation of the slow-release oxone preparation according to claim 1, wherein the thickness of the inner layer is 0.2mm, and the outer layer accounts for 0.2% of the total mass of the slow-release oxone preparation.
5. The use of the drug-loaded structure in the preparation of the slow-release oxone preparation according to claim 1, wherein the raw material components of the drug-loaded pellet core comprise oxone, a filler, a first plasticizer, sodium carboxymethylcellulose and water, and the mass ratio of the raw material components of the drug-loaded pellet core is as follows: 6 parts of potassium hydrogen persulfate, 15 parts of a filler, 4 parts of a first plasticizer, 0.05 part of sodium carboxymethyl cellulose and 5 parts of water;
the inner layer film comprises the following raw material components in percentage by mass: ethyl cellulose 15, a second plasticizer 3, a pore-forming agent 4, an organic solvent 80;
the raw material components of the outer layer film coat comprise hydroxypropyl methyl cellulose, a third plasticizer, potassium hydrogen persulfate and water, and the mass ratio of the components of the outer layer film coat is as follows: hydroxypropyl methylcellulose 5, third plasticizer 5, potassium hydrogen persulfate 2 and water 100.
6. Use of a drug-loaded structure according to any one of claims 1 to 5 in the preparation of a sustained release oxone formulation, wherein step (2) synthesizes an inner membrane coating solution: adding ethyl cellulose into an organic solvent, heating in a water bath, adding a second plasticizer while stirring, adding a pore-forming agent after stirring for 30 minutes, stirring until the ethyl cellulose is completely dissolved, and standing for 10 minutes under the water bath heating state to obtain an inner layer film coating solution;
synthesizing an outer-layer film coating solution in the step (3): adding hydroxypropyl methylcellulose and potassium hydrogen persulfate into water, heating in water bath, adding plasticizer III, heating in water bath, stirring for 30 min at room temperature until hydroxypropyl methylcellulose is completely dissolved, and standing at room temperature for 10min to obtain outer membrane solution.
7. The use of a drug-loaded structure in the preparation of a sustained-release oxone preparation according to any one of claims 1-5, wherein the number of times that the core of the drug-loaded pellet in step (4) is soaked in the inner layer coating solution is 2-6, and the number of times that the core of the drug-loaded pellet wrapped with the inner layer coating in step (4) is soaked in the outer layer coating solution is 2-3.
8. The use of a drug-loaded structure in the preparation of a sustained-release oxone formulation according to claim 7, wherein the number of times the core of the pellet wrapped with the inner layer membrane coat in step (4) is soaked in the inner layer membrane coat solution is 2, and the number of times the core of the pellet wrapped with the inner layer membrane coat in step (4) is soaked in the outer layer membrane coat solution is 2.
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| CN111480658B (en) * | 2020-04-17 | 2022-04-19 | 北京京蝠环保科技有限公司 | Long-acting solid mildew-proof deodorant |
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