Anti-sticking agent for coating liquid and preparation method of anti-sticking agent

Abstract

The invention discloses an anti-sticking agent for a coating solution and a preparation method of the anti-sticking agent, and belongs to the technical field of coatings, the effective component of the anti-sticking agent for the coating solution is fatty glyceride nanoparticles with the average particle size of less than 500nm, and the anti-sticking agent for the coating solution is a suspension or solid powder of the fatty glyceride nanoparticles; the fatty glyceride nanoparticles are prepared from fatty glyceride through an aqueous solvent diffusion method, wherein the fatty acid of the fatty glyceride is fatty acid with the carbon number of C16-C22. When the anti-sticking agent is used for preparing a coating solution, the use of an emulsifier or a cosolvent can be reduced, auxiliary material components are reduced, the compactness of a coating film is improved, the formed coating film is uniform in property and more uniformly dispersed in the coating solution, and the problem that the local content is too high can be avoided.

Description

Technical Field

[0001] The invention belongs to the technical field of coating, and particularly relates to an anti-sticking agent for coating liquid and a preparation method thereof. Background Art

[0002] Among pharmaceutical coating excipients, water dispersion coating liquid is a dispersion of polymer latex particles with a particle size of 0.01-0.1μm in water. It has low viscosity and is easy to spray coating. During the film-forming process, the latex particles form a stacking layer. As the water evaporates, the surface tension increases, causing the particles to gather tightly and form a film in an environment above the minimum film-forming temperature. It is widely used in gastric coatings, enteric coatings, sustained / controlled release coatings, protective isolation coatings, sustained-release skeleton materials, and skeleton adhesive materials for transdermal preparations, and is an important pharmaceutical preparation excipient.

[0003] Coating materials are usually used together with other excipients, such as plasticizers, anti-adherents, defoamers, etc. Aqueous dispersions are similar to colloids and are very sensitive to electrolytes, pH changes, heat, organic solvents and high shear forces, and are prone to latex particle aggregation. The influence of other excipients cannot be detected when they are first added to the aqueous dispersion, but often becomes obvious during the coating operation a few hours later, which can cause the coating operation to be terminated, seriously affecting the smooth progress of the coating process.

[0004] The coating liquid sprayed on the surface of the drug particles in the coating process becomes sticky with solvent evaporation, and adding an anti-adherent in the coating liquid can reduce viscosity and avoid mutual adhesion between the drug particles. Commonly used anti-adherents include: talcum powder, magnesium stearate and glyceryl monostearate. Wherein magnesium stearate can only be used for organic solvent coating liquid, because of its alkaline characteristics, especially can not be shared with the coating material dissolved under alkaline conditions such as Eutectic L30D-55, easily causing the coating film to rupture, on the other hand, magnesium stearate has hydrophobicity, also can block drug release. The most commonly used anti-adherent at present is talcum powder (such as publication number CN113546053A, CN114272385A, CN111920956A etc.), generally used in an amount of 25-200% of a polymer, and a common amount is 25-50%, and the amount is large, and often needs to add more solvents, so that the coating liquid volume is increased, and the coating process time is extended. In addition, even ultrafine (1000 mesh) talcum powder is very easy to settle, and continuous stirring is required during the coating process, which can easily lead to uneven distribution of talcum powder in the coating film, uneven and unstable quality of the coating film, and affect the coating quality.

[0005] Glyceryl monostearate is used as an anti-adhesive agent for aqueous dispersion coating liquid. It is not easy to settle. The common dosage is 2-10% of the polymer amount. The dosage is small, the volume of the coating liquid is small, and the coating time can be shortened. However, it has some disadvantages in use. For example, according to the recommendation of the Eudragit product manual, in the preparation of L30D-55 coating liquid with glyceryl monostearate as an anti-adhesive agent, glyceryl monostearate needs to be emulsified in 70-80℃ hot water with Tween 80 equivalent to about 2% of the polymer coating material, and the ratio of glyceryl monostearate to emulsifier Tween 80 is 2.5:1. The operation process is complicated, and the properties of the emulsions of glyceryl monostearate prepared by different personnel are not exactly the same, and the reproducibility is poor, which affects the coating quality. In addition, new auxiliary materials such as Tween 80 are introduced into the coating film, making the coating solution prescription and the composition of the final preparation more complicated; in addition, Tween 80 is easily soluble in water, which may increase the water permeability of the L30D-55 enteric coating film and decrease the acid resistance, which is not conducive to the density of the coating film. Summary of the invention

[0006] In view of the shortcomings of the above-mentioned prior art, the present invention provides an anti-sticking agent for a coating liquid, which can reduce the use of emulsifiers or co-solvents when preparing the coating liquid, reduce auxiliary material components, improve the density of the coating film, and form a coating film with uniform properties.

[0007] The specific technical solutions adopted are as follows:

[0008] The invention provides application of fatty acid glyceride nanoparticles as an anti-sticking agent for a coating solution.

[0009] The present invention also provides an anti-sticking agent for a coating liquid, wherein the effective component of the anti-sticking agent for a coating liquid is fatty acid glyceride nanoparticles with an average particle size of less than 500 nm, and the anti-sticking agent for a coating liquid is a suspension or solid powder of the fatty acid glyceride nanoparticles;

[0010] The fatty acid glyceride nanoparticles are prepared from fatty acid glyceride by an aqueous solvent diffusion method, wherein the fatty acid of the fatty acid glyceride is a fatty acid with a carbon number of C16 to C22.

[0011] Optionally, the anti-adherent agent for coating liquid is an anti-adherent agent for drug coating liquid, and the fatty acid glycerides include but are not limited to glyceryl monostearate, glyceryl distearate, glyceryl tristearate, glyceryl monopalmitate, glyceryl dipalmitate, glyceryl tripalmitate, glyceryl behenate, etc.

[0012] Preferably, the fatty acid glyceride is glyceryl monostearate and / or glyceryl distearate.

[0013] The present invention also provides a method for preparing the anti-adhesive agent for coating liquid, comprising the following steps: dissolving fatty acid glyceride in an organic solvent miscible with water to obtain an organic solution of fatty acid glyceride, adding the organic solution of fatty acid glyceride into water, and stirring during mixing to prepare a suspension containing the fatty acid glyceride nanoparticles, or mixing the organic solution of fatty acid glyceride and water using microfluidic technology to prepare a suspension containing the fatty acid glyceride nanoparticles.

[0014] Furthermore, pharmaceutical excipients (lyoprotectants, excipients, etc.) are added to the suspension containing fatty acid glyceride nanoparticles prepared by the above method, and the fatty acid glyceride nanoparticle solid powder is collected by freeze drying or spray drying. The fatty acid glyceride nanoparticle solid powder has a longer effective time.

[0015] When preparing the coating solution, the suspension containing fatty acid glyceride nanoparticles prepared by the above method can be directly used and prepared immediately, but the suspension must not be stored at room temperature for more than 48 hours; the fatty acid glyceride nanoparticle solid powder can also be re-dissolved to prepare the suspension.

[0016] Preferably, the organic solvent is selected from at least one of methanol, ethanol, dimethyl sulfoxide or ethyl acetate; and the concentration of the organic solution of fatty acid glyceride is 1-500 mg / mL.

[0017] The present invention also provides a water dispersion coating liquid, comprising the anti-sticking agent for the coating liquid. The water dispersion coating liquid can be used to coat a functional coating film on tablets, capsules or granules.

[0018] Preferably, the aqueous dispersion coating solution is composed of the following components in percentage by weight:

[0019] The coating solution contains 0.1-5% anti-adhesive agent;

[0020] Coating material 5-45%;

[0021] Plasticizer 0-5%;

[0022] The balance is water.

[0023] The coating material includes but is not limited to Eudragit L30D-55, L100-55, L100, E100, EPO, RL / RS series, NE / NM, FS or Series of polymers.

[0024] The plasticizer includes but is not limited to triethyl citrate, polyethylene glycol, propylene glycol, dibutyl sebacate and the like.

[0025] Optionally, a suspension containing the fatty acid glyceride nanoparticles is taken, diluted with water to a target solid content, stirred evenly, and set aside; or a solid powder of fatty acid glyceride nanoparticles is taken, redissolved with water and diluted to a target solid content, stirred evenly, and set aside. Subsequently, a suspension containing fatty acid glyceride nanoparticles with a target solid content, a uniformly dispersed plasticizer or pigment, etc., are added to a coating material dispersion under stirring to obtain a coating solution, which can be used to coat the preparation to form a coating film.

[0026] The present invention also provides a product, including a coating and contents (the contents can be selected as drug particles), wherein the coating is prepared from the aqueous dispersion coating liquid.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] (1) The present invention uses fatty acid glyceride nanoparticles as anti-sticking agents for the coating solution, which can reduce or completely eliminate the use of emulsifiers or cosolvents, reduce auxiliary material components, and improve the density of the coating film. The fatty acid glyceride nanoparticles prepared by the method of the present invention have a narrow particle size distribution and good size uniformity. The formed coating film has uniform properties and is more evenly dispersed in the coating solution, which can avoid the problem of excessive local content.

[0029] (2) Commercially available products HTP20 (fatty acid glyceride and plasticizer aqueous emulsion) is an aqueous suspension with a solid content of 20%, containing anti-adherent glyceryl monostearate, plasticizer triethyl citrate and emulsifier polysorbate. This product is a pre-formulated product. When used, it is shaken to reduce its viscosity, and then stirred and mixed with the coating material (polymer) dispersion for use. Compared with this product, the present invention uses fatty acid glyceride nanoparticles as an anti-adherent, does not need to add an emulsifier, and can independently adjust the amount of plasticizer added according to the prescription process requirements, and has a large operating space. The coating film made from the coating solution using fatty acid glyceride nanoparticles as an anti-adherent is more uniform in quality, has better density, and can quickly release drugs under pH conditions without interfering with drug dissolution. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a particle size distribution diagram of the suspension of fatty acid glyceride nanoparticles of different concentrations prepared in Example 1.

[0031] Figure 2 This is the particle size distribution diagram of the suspension of fatty acid glyceride nanoparticles with different concentrations prepared in Example 2.

[0032] Figure 3 This is a graph showing the effect of adding triethyl citrate on the particle size of fatty acid glyceride latex particles in Comparative Example 1.

[0033] Figure 4for Particle size distribution of HTP20.

[0034] Figure 5 Scanning electron micrographs of different free membrane cross sections.

[0035] Figure 6 The dissolution curves of different enteric-coated pellets. DETAILED DESCRIPTION

[0036] The present invention will be further described below in conjunction with the examples and drawings. It should be understood that these examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention. The operating methods in the following examples that do not specify specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturer. Contents not described in detail in this specification belong to prior art known to professionals and technicians in the field.

[0037] Example 1 Preparation of fatty acid glyceride nanoparticles by stirring method

[0038] Take 1000 mg of monostearate, add 10 ml of ethanol, heat at 50°C to dissolve the monostearate to prepare an ethanol solution of monostearate, pour the ethanol solution of monostearate into water under stirring, continue stirring for 5 minutes, and cool to room temperature to form a 10 mg / ml suspension of fatty acid glyceride nanoparticles.

[0039] Take 1500 mg of monostearate, add 10 ml of ethanol, heat at 50°C to dissolve the monostearate to prepare an ethanol solution of monostearate, pour the ethanol solution of monostearate into water under stirring, continue stirring for 5 minutes, and cool to room temperature to form a 15 mg / ml suspension of fatty acid glyceride nanoparticles.

[0040] Take 3000 mg of monostearate, add 10 ml of ethanol, heat at 50°C to dissolve the monostearate to prepare an ethanol solution of monostearate, pour the ethanol solution of monostearate into water under stirring, continue stirring for 5 minutes, and cool to room temperature to form a 30 mg / ml suspension of fatty acid glyceride nanoparticles.

[0041] Example 2 Preparation of fatty acid glyceride nanoparticles by microfluidics

[0042] Take 1500 mg of glyceryl monostearate, add 10 ml of ethanol, heat at 50°C to dissolve the glyceryl monostearate, and prepare an ethanol solution of glyceryl monostearate. Two active pumps assisted by heating equipment deliver water and ethanol solution of glyceryl monostearate at speeds of 27 ml / min and 3 ml / min, respectively. At 50°C, the liquids in the two channels are quickly mixed in the mixing chamber to prepare a 15 mg / ml suspension of fatty acid glyceride nanoparticles.

[0043] Take 2000 mg of glyceryl monostearate, add 10 ml of ethanol, heat at 50°C to dissolve the glyceryl monostearate, and prepare an ethanol solution of glyceryl monostearate. Two active pumps assisted by heating equipment deliver water and ethanol solution of glyceryl monostearate at speeds of 27 ml / min and 3 ml / min, respectively. At 60°C, the liquids in the two channels are quickly mixed in the mixing chamber to prepare a 20 mg / ml suspension of fatty acid glyceride nanoparticles.

[0044] Example 3 Particle size and stability determination of fatty acid glyceride nanoparticles

[0045] The suspension of fatty acid glyceride nanoparticles prepared by the stirring method in Example 1 has good light transmittance and presents a light blue opalescence. The higher the concentration, the lower the light transmittance. The particle size and distribution results are shown in Table 1. The concentration of fatty acid glyceride nanoparticles ranges from 10 mg / ml to 30 mg / ml, the average particle size is between 260 nm and 300 nm, the polydispersity index PDI is less than 0.3 or approximately equal to 0.3, and the particle size distribution diagram is shown in Table 1. Figure 1 The results show that the fatty acid glyceride nanoparticles are small, nano-sized, and have good uniformity.

[0046] In the suspension of fatty acid glyceride nanoparticles prepared by microfluidics, the particle size of fatty acid glyceride nanoparticles is similar to that prepared by stirring method, with a small increase. The particle size data are shown in Table 1, and the distribution diagram is shown in Figure 2 shown.

[0047] After being placed at room temperature for 6 hours, the stability results of the fatty acid glyceride nanoparticles of Example 1 are shown in Table 2. At a concentration of 10 mg / ml to 20 mg / ml, the particle size grows slightly, and the polydispersity index PDI is small, indicating that the fatty acid glyceride nanoparticles have good stability after being stored at room temperature for 6 hours. The particle size of the nano fatty acid glyceride of 30 mg / ml has a slight increase, the PDI is large, and the particle size is less than 500 nm, indicating that the particles are small, but the dispersion uniformity is slightly poor.

[0048] Table 1. Particle size and polydispersity coefficient of fatty acid glyceride nanoparticles

[0049]

[0050] Table 2. Particle size and polydispersity coefficient of the suspension of fatty acid glyceride nanoparticles after 6 h at room temperature

[0051]

[0052] Comparative Example 1: Preparation of anti-adhesive glyceryl monostearate emulsion according to the Eudragit manual

[0053] With reference to the preparation method of the anti-adherent agent in the enteric coating solution method of glyceryl monostearate as an anti-adherent agent in the manual of Eutectic, the prescription composition is shown in Table 3, and the specific preparation method is as follows: 40% of the water is heated to 70-80°C, a homogenizer is used, polysorbate 80 (Tween80) solution (33% aqueous solution), triethyl citrate and glyceryl monostearate are added to hot water, uniformly mixed for 10 minutes, the solid content is 15%, and a small amount of dimethyl silicone oil emulsion can be added as a defoamer when necessary to remove foam and obtain glyceryl monostearate emulsion. According to the liquid amount in Table 3, the volume is made up to a concentration of about 8.5mg / ml of glyceryl monostearate.

[0054] Table 3. Composition of enteric coating solution with glyceryl monostearate as anti-adhesive agent

[0055]

[0056] The glyceryl monostearate emulsion is white and has poor light transmittance. Its concentration is much lower than the suspension of fatty acid glyceride nanoparticles prepared in Examples 1 and 2. Compared with Examples 1 and 2, its light transmittance is the worst, indicating that its particles are the largest.

[0057] After the emulsion was diluted, its particle size was measured to be 1130nm and the polydispersity coefficient was 0.325. Considering that triethyl citrate has poor water solubility and may affect the particle size of monostearate glycerol emulsion droplets, the above emulsion preparation method was referred to, but triethyl citrate was removed, and the obtained emulsion particle size was 805nm. The particle size was reduced, but the PDI value increased, indicating that the dispersion was uneven. The particle size distribution is as follows Figure 3 and Table 4. The results showed that the glyceryl monostearate emulsion prepared according to the manual method had a large particle size and poor uniformity.

[0058] Table 4. Particle size and polydispersity coefficient of glyceryl monostearate emulsion

[0059]

[0060] Commercially available anti-adhesive agents After HTP20 dilution, the particle size measurement results are as follows Figure 4 As shown, the particle size is large, about 1500nm.

[0061] Example 4 Fatty acid glyceride nanoparticles used as anti-adhesive agent to prepare coating solution

[0062] Table 5. Composition of enteric coating solution with fatty acid glyceride nanoparticle suspension as anti-adhesive agent

[0063]

[0064] According to the above table, add the fatty acid glyceride nanoparticle suspension, plasticizer and water into the Eudragit L30D-55 dispersion, stir with a stirrer for 10 minutes, and pass the suspension through a 0.5 mm sieve to obtain an enteric coating solution for later use.

[0065] Comparative Example 2 Commercially available HTP20 is used as an anti-sticking agent to prepare coating liquid

[0066] Table 6. The formula composition of enteric coating solution with HTP20 as anti-adhesive agent

[0067]

[0068] HTP20 is a thixotropic liquid and must be shaken before use to reduce its viscosity. HTP20 was added to the Eudragit dispersion, stirred with a stirrer for 10 min, and the suspension was passed through a 0.5 mm sieve for later use.

[0069] Example 5 Preparation of free film and investigation of moisture permeability

[0070] Prepare enteric coating liquid with reference to the formula of Table 3, Table 5 and Table 6, prepare three kinds of free films by casting film method, measure about 30mL coating liquid respectively, pour into horizontally placed square box with polytetrafluoroethylene material at the bottom and size of 15.0cm×15.0cm×1.0cm, stand at room temperature until semi-solid state, stand in 30℃ oven until polymer dries into uniform and dense film. Then transfer to a desiccator (saturated KNO3 solution) with relative humidity of about 92.5% to soften it by moisture absorption. Remove the film, put it in a 30℃ oven again for drying, then move to a desiccator (saturated K2CO3 solution) with relative humidity of about 43% to store for testing, and name them as emulsion anti-adhesive film, nano anti-adhesive film and PlasACRYL film respectively.

[0071] The cup method is used to measure the moisture permeability of the free film. Take a number of vials, grind the bottle mouths, and put a sufficient amount of color-changing silica gel in the bottle as a moisture absorbent. Use glue to seal the free film on the bottle mouth, leave it at room temperature, let the glue dry, cut off the excess film on the edge of the bottle mouth, and grind it flat. After precise weighing, place the vial in a dryer (saturated KNO3 solution) at (25±2)℃ and RH of about 92.5%, and take out the vial at 12, 24, 36, 48, 60, and 72 hours, respectively, and weigh it. Calculate the film moisture permeability coefficient according to Fick's first law:

[0072] Q=K×ΔP×A×T / L

[0073] Where Q is the moisture permeability (g), K is the moisture permeability coefficient of the membrane (g·mm·kPa -1 ·m -2 ·h -1 ), ΔP is the water vapor partial pressure difference on both sides of the membrane (kPa), A is the moisture permeability area (m 2 ), T is the moisture permeability time (h), L is the thickness of the film (mm). The free film is sealed at the bottle mouth, and one side of the film is a substance with drying properties (color-changing silica gel), whose water vapor partial pressure is small and can be approximated to zero. At this time, ΔP is approximately equal to the vapor pressure P on the other side (P = ΦP0, Φ is the relative humidity of air, and P0 is the saturated vapor pressure of water). Linear regression is performed on Q against T, and the moisture permeability coefficient K can be calculated from the slope. The larger the moisture permeability coefficient K value, the stronger the moisture permeability of the free film and the worse the density.

[0074] After measurement, the value of the moisture permeability coefficient K is shown in Table 7:

[0075] Table 7 Free film moisture permeability coefficient

[0076]

[0077] From the results in the table above, we can see that the moisture permeability coefficient is emulsion anti-adhesive film>PlasACRYL film>nano anti-adhesive film, indicating that the nano anti-adhesive film made of enteric coating liquid with fatty acid glyceride nanoparticle suspension as anti-adhesive agent has the best density, which is better than PlasACRYL film and emulsion anti-adhesive film. The cross-sectional scanning electron microscopy results of the three films are shown in Figure 2. Figure 5 As shown, it can be seen that the nano anti-adhesive film has the best density.

[0078] Example 6 Application of Nano-fatty acid glyceride anti-adherent coating solution in preparing coated micropellets

[0079] Pantoprazole sodium was used as a model drug to prepare pantoprazole sodium-containing pellets. Enteric coating solutions were prepared using the formulas and preparation methods in Tables 3, 5, and 6. The same weight of enteric coating solution with glyceryl monostearate as an anti-adhesive agent, Pantoprazole sodium micropellets were coated with enteric coating liquid containing HTP20 as an anti-adhesive agent and enteric coating liquid containing fatty acid glyceride nanoparticle suspension as an anti-adhesive agent to prepare pantoprazole sodium enteric micropellets, which were named No. 1 micropellets, No. 2 micropellets and No. 3 micropellets respectively. The coating parameters were the same as follows: material temperature 28°C, air inlet temperature 37-39°C, atomization pressure 0.15, air volume 17-19m 3 / h. The coating process is smooth without any blockage or sticking.

[0080] The acid resistance test was used to examine the protection of the enteric-coated micropellets on the drug and to determine the quality of the coating film. The test method is as follows: According to the first method of the fourth dissolution test method of the Chinese Pharmacopoeia 2020, the speed was 100rpm and the temperature was (37±0.5)℃. Take the enteric-coated micropellets, accurately weigh them, and use 900ml of 0.1mol hydrochloric acid solution as the dissolution medium, and operate according to the law. After 2h, the dissolution medium was discarded, the rotating basket was removed, the micropellets were collected, the rotating basket was washed with deionized water several times until the washing liquid was neutral, and then rinsed with 0.001mol sodium hydroxide solution-acetonitrile (1:1.v:v), and the contents in the rotating basket were quantitatively transferred to a 100mL volumetric flask. Pantoprazole sodium was dissolved by water bath ultrasound, cooled, diluted with solvent, and fixed to volume. Centrifuge at 12000rpm for 10min, accurately measure 5mL of supernatant, add solvent to a 50mL volumetric flask for dilution, and make up to volume as the test solution. Determine the drug content by HPLC, and calculate the remaining drug content after 2h. The results are shown in Table 8, which show that No. 2 and No. 3 pellets have better protective effects on drugs.

[0081] Table 8 The protective effect of the coating films prepared by different coating solutions on drugs

[0082]

[0083] The dissolution test determines the dissolution of the drug in PBS solution with a pH of 6.8, which is a simulated intestinal fluid. The test method is as follows: Determine according to the first method of the dissolution test method in Part 4 of the Chinese Pharmacopoeia 2020, with a rotation speed of 100 rpm and a temperature of (37±0.5)°C. Take an appropriate amount of pantoprazole sodium pellets, accurately weigh them, use 900 mL of pH 6.8 PBS solution as the dissolution medium, operate according to the law, take samples at 5, 10, 15, 20, 25, 30, 45, and 60 minutes, filter with a 0.45um filter membrane, and determine the absorbance at a wavelength of 288nm by ultraviolet spectrophotometry. Substitute the absorbance into the standard curve equation to calculate the corresponding drug concentration and cumulative drug release percentage. The results are as follows. Figure 6 As shown, the No. 3 micropellets prepared with nano anti-adhesive agents can quickly respond to the pH environment, quickly release the drug, do not affect the dissolution of the drug, and achieve rapid onset of action.

[0084] The enteric coating film prepared from fatty acid glyceride nanoparticles can effectively protect the stability of drugs in acidic environments. The density of the enteric coating film is better than that of emulsion anti-adhesive agents and commercially available PlasACRYL anti-adhesive agents, and it can quickly release drugs under pH conditions without interfering with drug dissolution.

[0085] The embodiments described above provide a detailed description of the technical solutions of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, supplements or similar substitutions made within the scope of the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. Application of fatty acid glyceride nanoparticles as anti-adhesive agents for coating solutions.

2. An anti-adherent agent for a coating solution, characterized in that: The active ingredient of the anti-adhesive agent for coating liquid is fatty acid glyceride nanoparticles with an average particle size of less than 500 nm, and the anti-adhesive agent for coating liquid is a suspension or solid powder of the fatty acid glyceride nanoparticles; The fatty acid glyceride nanoparticles are prepared from fatty acid glyceride by an aqueous solvent diffusion method, wherein the fatty acid of the fatty acid glyceride is a fatty acid with a carbon number of C16 to C22.

3. The anti-adherent agent for coating solution according to claim 2, characterized in that: The anti-adhesive agent for coating liquid is an anti-adhesive agent for drug coating liquid, and the fatty acid glyceride includes glyceryl monostearate, glyceryl distearate, glyceryl tristearate, glyceryl monopalmitate, glyceryl dipalmitate, glyceryl tripalmitate or glyceryl behenate.

4. The anti-adherent agent for coating solution according to claim 3, characterized in that: The fatty acid glyceride is glyceryl monostearate and / or glyceryl distearate.

5. The method for preparing the anti-adherent agent for coating solution according to any one of claims 2 to 4, characterized in that: The following steps are involved: The fatty acid glyceride is dissolved in an organic solvent miscible with water to obtain an organic solution of the fatty acid glyceride; the organic solution of the fatty acid glyceride is added to water and stirred during mixing to prepare a suspension containing the fatty acid glyceride nanoparticles, or the organic solution of the fatty acid glyceride and water are mixed using microfluidic technology to prepare a suspension containing the fatty acid glyceride nanoparticles.

6. The method for preparing the anti-adherent agent for coating solution according to claim 5, characterized in that: The organic solvent is selected from at least one of methanol, ethanol, dimethyl sulfoxide or ethyl acetate; the concentration of the organic solution of fatty acid glyceride is 1-500 mg / mL.

7. An aqueous dispersion coating solution, characterized in that: The invention comprises the anti-adhesive agent for coating solution according to any one of claims 2 to 4.

8. The aqueous dispersion coating liquid according to claim 7, characterized in that: It is composed of the following ingredients in percentage by weight: The coating solution contains 0.1-5% anti-adhesive agent; Coating material 5-45%; Plasticizer 0-5%; The balance is water.

9. A product, characterized in that The invention comprises a coating and contents, wherein the coating is prepared from the water dispersion coating liquid according to claim 7 or 8.

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