Human respiratory tract bionic coating liquid as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of biological medicine, particularly relates to bionic coating liquid as well as a preparation method and application thereof, and more particularly relates to bionic coating liquid with physicochemical properties close to those of human respiratory tract liquid, which is used for a coating on the inner wall of a human respiratory system bionic model constructed by a 3D printing technology. A model close to a human physiological environment can be constructed to eliminate bounce of particles so as to better capture deposited drugs, and research on distribution and deposition of inhaled preparations in a human body, research and development of innovative drugs of the inhaled preparations, research on consistency evaluation of imitated drugs and the like can be carried out.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and in particular, relates to a human respiratory tract biomimetic coating liquid and a preparation method and application thereof. Background Art

[0002] The aerodynamic properties of fine particles are important quality indicators for inhalation dosage forms. Currently, the classic cascade impactor method is the dominant method. However, the structure of a cascade impactor is not similar to that of the human respiratory system, and this method cannot accurately reflect the deposition and distribution of drug particles in various parts of the human respiratory system. Biomimetic models of the human respiratory system constructed using 3D bioprinting technology more closely resemble the actual structure of the human respiratory system and can more accurately reflect the deposition and distribution of drug particles in various parts of the human respiratory system. Therefore, they are increasingly being used to study the aerodynamic properties of inhalation dosage forms.

[0003] The surface of the respiratory system bionic model constructed based on biological 3D printing technology needs to be coated with a viscous liquid to simulate the respiratory mucus in the body to eliminate the bouncing of particles and thus better capture and deposit them. Currently, glycerol or silicone oil is mostly used as the coating liquid. However, the composition, pH value, viscosity and other physical and chemical properties of single glycerol or silicone oil are different from those of the respiratory mucus in the human body, and cannot truly reflect the physiological environment of the human respiratory system.

[0004] Therefore, there is an urgent need to develop a bionic coating liquid that can better simulate human respiratory mucus. Summary of the Invention

[0005] In order to solve at least one of the above problems, the present invention intends to prepare a bionic coating liquid with physical and chemical properties close to those of human respiratory mucus, which is used for coating the inner wall of a bionic model of the human respiratory system constructed using 3D printing technology, thereby constructing a model that is closer to the human physiological environment for the study of the aerodynamic characteristics of fine particles in inhaled preparations.

[0006] To this end, the present invention provides a biomimetic coating liquid on one hand, wherein the components of the biomimetic coating liquid include mucin and a nonionic surfactant.

[0007] The present invention prepares a bionic coating liquid with physical and chemical properties close to those of human respiratory fluid, which is used for coating the inner wall of a bionic model of the human respiratory system constructed using 3D printing technology. This model, which is closer to the human physiological environment, can be used to eliminate the bouncing of particles to better capture deposited drugs. It can also be used to study the distribution and deposition of inhalation preparations in the body, develop innovative inhalation preparations, and evaluate the consistency of generic drugs.

[0008] According to a specific embodiment of the present application, the mucin includes at least one originating from the lungs, eyes, mouth, small intestine, and stomach.

[0009] According to a specific embodiment of the present application, the mass percentage concentration of the mucin in the bionic coating liquid is 0.4-1%. The bionic coating liquid prepared within this range is more in line with the physiological environment of the human body.

[0010] According to the specific implementation scheme of the present application, the nonionic surfactant includes at least one of polyethylene glycol and polyethylene oxide lauryl ether. Preferably, the nonionic surfactant is polyethylene oxide lauryl ether, and the mass percentage concentration of polyethylene oxide lauryl ether in the bionic coating liquid is 0.6-1.5%. The bionic coating liquid prepared within this range has good stability and is not prone to sedimentation, thereby affecting the experimental results, and can improve the reliability of the simulation results. It should be noted that all design ideas that are the same as those of the present application are within the scope of patent protection of the present application. For example, the stabilizer selected in the present application is a nonionic surfactant, more specifically polyethylene oxide lauryl ether, but it does not mean that only polyethylene oxide lauryl ether is suitable for the present application. Those skilled in the art can expand the screening and screen out other nonionic surfactants with the same or similar functions as polyethylene oxide lauryl ether.

[0011] According to a specific embodiment of the present application, the biomimetic coating liquid further includes glycerol, which can be used as the main solvent of the coating liquid to adjust the viscosity of the coating liquid to make it closer to the viscosity of human respiratory mucus.

[0012] According to a specific embodiment of the present application, the volume percentage of the glycerol in the bionic coating liquid is 43-78%. The bionic coating liquid prepared within this range is more consistent with the physiological environment of the human body.

[0013] According to a specific embodiment of the present application, the pH of the biomimetic coating liquid is 7.1-7.8.

[0014] The reference range of serum viscosity is 1.5-2 mPa.s. With the development of microfluidics in recent years, it has been shown that the viscosity of human respiratory mucus under wet conditions is about 5-20 times that of serum (Rubinstein et al. al., 2013), therefore, the viscosity of normal human respiratory mucus ranges from 7.5 to 40 mPa.s. Glycerol is a colorless, non-toxic, viscous liquid and is one of the common moisturizers. It is also used in respiratory coating fluids. However, traditional respiratory coating fluids are usually 100% glycerol, which is quite different from the physical and chemical properties of human respiratory coating fluids. The inventors of this application have screened out the optimal glycerol volume percentage (43%-78%) in the coating fluid by exploring the glycerol concentration. However, the ordinary coating fluid prepared with pure glycerol, even if its viscosity is similar to that of the human respiratory tract, still cannot simulate the interaction between exogenous molecules and proteins in the human respiratory tract. Moreover, the ordinary coating fluid without the addition of mucin will form a large number of bubbles on the inner wall of the bionic model, resulting in insufficient surface tension and failure to achieve the biomimetic effect. Therefore, the inventors added human respiratory tract to the improved coating fluid. The inventors made improvements to the protein (mucin) that accounts for the largest proportion in the human respiratory tract. During the trial process, the inventors found that the bionic coating liquid with further addition of mucin would show sedimentation after being placed for a long time and was extremely unstable. Therefore, the inventors added a non-ionic surfactant to the bionic coating liquid and screened out a non-ionic surfactant that is most suitable for the bionic coating liquid of this application. Finally, the inventors of this application further verified that the bionic coating liquid prepared in this application has characteristics close to the physical and chemical properties of human respiratory tract fluid through the study of the distribution and deposition of inhalation preparations in the body, and can be used for coating the inner wall of the bionic model of the human respiratory system constructed by 3D printing technology, and constructing a model that is closer to the human physiological environment to eliminate the bouncing of particles to better capture deposited drugs. It can also be used for research on the distribution and deposition of inhalation preparations in the body, the development of innovative inhalation preparations, and the consistency evaluation of generic drugs.

[0015] The second aspect of the present application provides a method for preparing the biomimetic coating liquid of the first aspect, comprising:

[0016] Follow these steps:

[0017] S1. dissolving and mixing mucin and a nonionic surfactant in a buffer solution to obtain a mixed solution;

[0018] S2, mixing the mixed solution with glycerol in a volume ratio of 1: (0.75-3) to obtain a biomimetic coating solution,

[0019] in,

[0020] The nonionic active agent is at least one of polyethylene oxide lauryl ether and polyethylene glycol.

[0021] According to a specific embodiment of the present invention, the biomimetic coating liquid prepared by the method of the present application has a mucus protein content of 0.67%, a volume proportion of glycerol of about 43-78%, and a concentration of polyethylene oxide lauryl ether of about 1%, which is closest to the physical and chemical properties of human respiratory mucus.

[0022] According to the specific implementation scheme of the present application, the mass percentage concentration of the mucin in the bionic coating liquid is 0.4-1%. Within this range, it can not only simulate the interaction between molecular drugs and proteins, but also increase the tension of ordinary bionic liquid. The prepared bionic coating liquid is more in line with the physiological environment of the human body.

[0023] According to a specific embodiment of the present application, the mass percentage concentration of the polyethylene oxide lauryl ether in the bionic coating liquid is 0.6-1.5%. The bionic coating liquid prepared within this range is more in line with the physiological environment of the human body.

[0024] According to the specific implementation scheme of the present application, the buffer solution is a phosphate buffer solution. It should be noted that the buffer solution here is not limited, and any buffer solution that is suitable for the human body is applicable to the present application.

[0025] According to a specific embodiment of the present application, the pH of the biomimetic coating liquid is 7.1-7.8.

[0026] According to a specific embodiment of the present application, the bionic coating liquid is a human respiratory tract bionic coating liquid.

[0027] The third aspect of the present application provides the use of the bionic coating liquid described in the first aspect in constructing a bionic model of the respiratory system.

[0028] According to the specific implementation scheme of the present application, the respiratory system bionic model is a structural model constructed based on 3D printing technology. The bionic coating liquid of the present application is more compatible with the structural model constructed by 3D printing technology, and is preferably a respiratory system structural model.

[0029] According to a specific embodiment of the present application, the respiratory system bionic model is used for studying the distribution and deposition of inhaled preparations in vivo.

[0030] The present invention prepares a bionic coating liquid with physical and chemical properties close to those of human respiratory fluid, which is used for coating the inner wall of a bionic model of the human respiratory system constructed using 3D printing technology. This model, which is closer to the human physiological environment, can be used to eliminate the bouncing of particles to better capture deposited drugs. It can also be used to study the distribution and deposition of inhalation preparations in the body, develop innovative inhalation preparations, and evaluate the consistency of generic drugs.

[0031] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the following description of the embodiments with reference to the accompanying drawings, in which:

[0033] Figure 1 This is a schematic diagram of the structure of the respiratory system bionic model in Example 5 of the present application;

[0034] Figure 2 This is a graph showing the drug deposition analysis results of the tiotropium bromide inhalation spray and inhalation powder in Example 5 of the present application;

[0035] Figure 3 This is the situation of the ordinary coating liquid in the inner wall of the bionic model in Example 5 of the present application. DETAILED DESCRIPTION

[0036] The embodiments of the present invention are described in detail below, and examples of the embodiments are shown in the accompanying drawings. The embodiments described below with reference to the accompanying drawings are exemplary and intended to be used to explain the present invention, but should not be understood as limiting the present invention.

[0037] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of the technical features being referred to. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "plurality" means at least two, such as two, three, etc., unless otherwise specifically defined.

[0038] As used herein, the terms "approximately" or "substantially" or "substantially" may mean that a value includes the standard deviation of the error of the device or method used to determine the value. The numerical ranges and parameters used to define the present invention are all approximate values, and the relevant numerical values in the specific embodiments have been presented as accurately as possible. However, any numerical value inherently inevitably contains a standard deviation caused by the aforementioned testing device or method. Therefore, unless otherwise expressly stated, it should be understood that all ranges, quantities, values and percentages used in the present invention are modified by "approximately". Here, "approximately" generally means that the standard deviation of the actual value and the theoretical model or theoretical data is within 3%, preferably 2%, and more preferably 1%.

[0039] The endpoints of the ranges and any values disclosed herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0040] Terms and Definitions

[0041] In order to make the present invention more easily understood, certain technical and scientific terms are specifically defined below. Unless otherwise clearly defined elsewhere in this document, all other technical and scientific terms used herein have the meaning commonly understood by those skilled in the art to which the present invention belongs.

[0042] In the present invention, the term "bio3D printing" is an emerging technology, which refers to the use of "three-dimensional printing" technology to produce personalized in vitro three-dimensional biological structure models according to the requirements of biomimetic morphology, organism function, or cell-specific microenvironment.

[0043] In this application, the term "structural model" refers to three-dimensional biological structures in biology, such as organoids created using 3D bioprinting. These models can mimic the genetic and epigenetic characteristics of target tissues or organs and have broad application prospects in various fields.

[0044] For the purposes of this invention, the term "mucin" refers to a large glycoprotein secreted by animal epithelial cells. They constitute the primary structural component of mucus and possess viscoelastic, lubricating, and moisturizing properties. Approximately 80% of the molecular weight of mucin is composed of oligosaccharide chains attached to threonine, serine, or proline residues in the protein core via O-glycosidic bonds. At the amino and carboxyl termini, these regions are rich in cysteine and extensively cross-linked via disulfide bonds. Mucins form a protective layer on the mucosal surface, protecting the mucosa from chemical, enzymatic, and mechanical damage. They also possess adhesive properties, capable of adhering to other substances through hydrogen bonds, hydrophobic interactions, and electrostatic interactions to form gel-like aggregates. Mucins physiologically play a role in protecting and lubricating epithelial surfaces, maintaining epithelial integrity, facilitating cell adhesion, and providing protection against the invasion of pathogens, toxins, and foreign particles.

[0045] In the present invention, the term "polyoxyethylene lauryl ether", also known as Brij-35, is a nonionic surfactant whose chemical name is polyoxyethylene lauryl ether. It is a polyoxyethylene compound generated by the reaction of ethylene oxide and lauryl alcohol and is widely used in detergents, emulsifiers, leveling agents and other fields.

[0046] The reference range of serum viscosity is 1.5-2 mPa.s. With the development of microfluidics in recent years, it has been shown that the viscosity of human respiratory mucus under wet conditions is about 5-20 times that of serum (Rubinstein et al., 2013). Therefore, the viscosity of normal human respiratory mucus ranges from 7.5-40 mPa.s. Glycerol is a colorless, non-toxic viscous liquid and is one of the common moisturizers. It is also used in respiratory coating fluids. However, traditional respiratory coating fluids are usually 100% glycerol, which has significant differences in physical and chemical properties from human respiratory coating fluids. The inventors of this application have screened out the optimal glycerol volume percentage (43%-78%) in the coating fluid through exploration of glycerol concentration. However, pure glycerol, even if its viscosity is similar to that of the human respiratory tract, still cannot simulate the interaction between exogenous molecules and proteins in the human respiratory tract. Therefore, the inventors added the protein (mucin) that accounts for the largest proportion in the human respiratory tract to the improved coating fluid in order to achieve a biomimetic effect. The inventors have tried a large number of The inventors conducted tests and found that the bionic coating liquid containing only mucin would settle after being placed for a long time and was extremely unstable. Therefore, the inventors further added a non-ionic surfactant to the bionic coating liquid and screened out a non-ionic surfactant that was most compatible with the bionic coating liquid of the present application. Finally, the inventors of the present application further verified that the bionic coating liquid prepared in the present application has characteristics close to the physical and chemical properties of human respiratory fluid through the study of the distribution and deposition of inhalation preparations in the body. It can be used for coating the inner wall of a bionic model of the human respiratory system constructed by 3D printing technology, and for constructing a model that is closer to the human physiological environment to eliminate the bouncing of particles to better capture deposited drugs. It can also be used for research on the distribution and deposition of inhalation preparations in the body, the development of innovative inhalation preparations, and the consistency evaluation of generic drugs.

[0047] The purpose of the present invention is to use a bionic model of the human respiratory system constructed using 3D printing technology to study the aerodynamic characteristics of fine particles of inhalation preparations. The bionic coating liquid prepared by the present invention is coated on the inner wall of the bionic model to establish a system model close to the human physiological environment, which is used to eliminate the bouncing of particles to better capture deposited drugs. The distribution and deposition of inhalation preparations in the body can be studied, and it is suitable for the research and development of innovative inhalation preparations and the consistency evaluation of generic drugs.

[0048] The present invention will be explained below in conjunction with the embodiments. Those skilled in the art will understand that the following embodiments are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. Where specific techniques or conditions are not specified in the examples, the techniques or conditions described in the literature in this field or in accordance with the product instructions are used. The following are the purchase sources and product numbers of the main reagents and consumables used in the examples of the present invention.

[0049] Mucin, purchased from Merck, catalog number M2378;

[0050] Polyoxyethylene lauryl ether (brij35), purchased from Merck, batch number S8405062406;

[0051] Glycerol (propylene glycol) was purchased from Sinopharm Group, batch number 20240522.

[0052] In the present invention, the viscosity test was performed using a rotary viscometer, model RheolabQC, purchased from Anton Paar, at a test temperature of 37° C. All reagents or instruments used without manufacturer indicated were commercially available conventional products.

[0053] Example 1

[0054] The coating solution was prepared according to the ratio shown in Table 1, and the viscosity and pH value of the coating solution were measured. The results showed that when the volume percentage of glycerol in the coating solution was 43-78%, the viscosity of the prepared coating solution was closest to the viscosity of human respiratory tract mucus (7.5-40 mPa.s).

[0055] Table 1

[0056] sample Phosphate buffer (ml) 100% glycerol (ml) Viscosity (mPa.s) pH value 1 100 200 14.6 7.32 2 100 75 6.83 7.19 3 100 300 30.5 7.45 4 100 350 40.2 7.63

[0057] Example 2

[0058] Taking sample 1 in Example 1 as an example, a biomimetic coating liquid was prepared by the following method:

[0059] 1) Add mucin and polyoxyethylene lauryl ether (Brij35) to 100 ml of phosphate buffer (pH 7.6) and stir to dissolve.

[0060] 2) The solution prepared in step 1) was mixed with glycerol in a volume ratio of 1:2 to obtain a biomimetic coating solution.

[0061] The components were adjusted according to the ratio shown in Table 2, and the viscosity, pH value and stability of the prepared biomimetic coating liquid were measured. Among them, the stability was determined by measuring the transmittance of 50 ml of the biomimetic coating liquid at a wavelength of 420 nm before and after standing for 3 hours. The best result was a transmittance change of less than 1% in 3 hours.

[0062] Table 2

[0063]

[0064] The respiratory tract of a healthy adult secretes about 10–100 mL of mucus per day, containing about 0.2–5 g of mucin. As shown in Table 2, the bionic coating liquid prepared in this application has a total mucin content of 0.67%, which is consistent with the bionic respiratory physicochemical properties. On this basis, the bionic coating liquid without non-ionic surfactants has poor stability and is easy to settle after standing. When the mass concentration of non-ionic surfactants in the bionic coating liquid is about 1%, the stability of the bionic coating liquid can be greatly improved.

[0065] Example 3

[0066] Tween 20 is a common nonionic surfactant and a viscous liquid. A biomimetic coating solution using Tween 20 as the primary solvent was prepared as shown in Table 3. The diluent used was a phosphate buffer solution. The results showed that while Tween 20 possesses some characteristics of both glycerol and nonionic surfactants, its viscosity after dilution cannot be precisely adjusted, resulting in either excessively high or low viscosity. This makes it a poor substitute for glycerol or poly(ethylene oxide) lauroyl ether.

[0067] Table 3

[0068]

[0069]

[0070] Example 4

[0071] The nonionic surfactant in Example 2 was replaced by polyethylene glycol 400 from polyethylene oxide lauryl ether. The test results are shown in Table 4. Within 3 hours, the change in transmittance was 2% or more, indicating that even though both are nonionic surfactants, the effect of polyethylene glycol 400 is still not as good as polyethylene oxide lauryl ether.

[0072] Table 4

[0073]

[0074] From Examples 1-4, it can be seen that when the mucus protein concentration in the prepared biomimetic coating is about 0.67%, the volume proportion of glycerol is about 43-78%, and the concentration of polyethylene oxide lauryl ether is about 1%, which is closest to the physical and chemical properties of human respiratory mucus.

[0075] Example 5

[0076] Three batches of tiotropium bromide inhalation spray (Spirivar, specification: 2.5 μg / dose, 2 doses / inhalation) and three batches of tiotropium bromide inhalation powder (Spirivar Respimat, specification: 18 μg / dose, 1 dose / inhalation) were taken respectively, and the aerodynamic characteristics of each fine particle inhalation were studied in a 3D printed human respiratory system bionic model (the model data was obtained from the computed tomography (CT) image of the subject approved by the Institutional Review Board of the Second Affiliated Hospital of Xi'an Jiaotong University, and commissioned by Southeast University) coated with the bionic coating liquid prepared by sample 5 of the present invention. The drug deposition amount in the left and right lung parts of the respiratory system bionic model was collected and measured. The bionic model is shown in FIG. Figure 1 , the measurement results are as follows Figure 2 As shown in the results, the average lung deposition of tiotropium bromide inhalation spray (5 μg / inhalation) was 0.63 μg (n=33), and the average lung deposition of tiotropium bromide inhalation powder (18 μg / inhalation) was 0.68 μg (n=33), with no significant difference between the two (p>0.05), which is consistent with the results of the literature "Wise RA, Anzueto A, Cotton D, et al. Tiotropium Respimat inhaler and the risk of death in COPD. [J]. N Engl J Med, 2013, 369 (16): 1491-1501.", while the ordinary coating solution without adding mucin formed a large number of bubbles on the inner wall of the bionic model ( Figure 3 ), it can be seen that mucin has a great influence on the surface tension of the coating liquid. The addition of mucin makes the coating liquid closer to the physical and chemical properties of the human body, and can more truly reflect the physiological environment of the respiratory system in the human body. It is proved that the bionic coating liquid prepared by the method of the present application can be used to study the distribution and deposition of inhalation preparations in the body, and is suitable for the research and development of innovative inhalation preparations and the consistency evaluation of generic drugs.

[0077] In summary, applying the biomimetic coating fluid prepared in this application to the inner wall of a biomimetic model can establish a system model that closely resembles the human physiological environment, eliminating particle bounce and better capturing and depositing the drug. The biomimetic coating fluid prepared in this application can be used to study the distribution and deposition of inhalation preparations in the body and is suitable for the development of innovative inhalation preparations and the consistency evaluation of generic drugs.

[0078] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0079] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention.

Claims

1. A biomimetic coating liquid, characterized in that: The components of the biomimetic coating liquid include mucin and non-ionic surfactant.

2. The biomimetic coating liquid according to claim 1, characterized in that The mucus protein includes at least one of the mucus protein originating from the lungs, eyes, mouth, small intestine, and stomach; Optionally, the mass percentage concentration of the mucin in the biomimetic coating liquid is 0.4-1%.

3. The biomimetic coating liquid according to claim 1, characterized in that The nonionic active agent includes at least one of polyethylene glycol and polyethylene oxide lauryl ether; Optionally, the mass percentage concentration of polyethylene oxide lauryl ether in the biomimetic coating liquid is 0.6-1.5%.

4. The biomimetic coating liquid according to claim 1, characterized in that The biomimetic coating solution further includes glycerol; Optionally, the volume percentage of the glycerol in the biomimetic coating liquid is 43-78%.

5. The biomimetic coating liquid according to claim 1, characterized in that The pH value of the biomimetic coating liquid is 7.1-7.

8.

6. A method for preparing the biomimetic coating liquid according to any one of claims 1 to 5, characterized in that: include: S1. dissolving and mixing mucin and a nonionic surfactant in a buffer solution to obtain a mixed solution; S2, mixing the mixed solution with glycerol in a volume ratio of 1: (0.75-3) to obtain a biomimetic coating solution, in, The nonionic active agent includes at least one of polyethylene glycol and polyethylene oxide lauryl ether.

7. The method according to claim 6, characterized in that The mass percentage concentration of the mucin in the biomimetic coating liquid is 0.4-1%; Optionally, the mass percentage concentration of the polyethylene oxide lauryl ether in the biomimetic coating solution is 0.6-1.5%; Optionally, the buffer is a phosphate buffer; Optionally, the pH of the biomimetic coating solution is 7.1-7.

8.

8. The method according to claim 6, characterized in that The bionic coating liquid is a human respiratory tract bionic coating liquid.

9. Use of the bionic coating liquid according to any one of claims 1 to 5 in constructing a bionic model of the respiratory system.

10. The use according to claim 9, characterized in that The respiratory system bionic model is a structural model constructed based on 3D printing technology; Optionally, the respiratory system biomimetic model is used for in vivo distribution and deposition studies of inhaled formulations.

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