Nasal protective gel as well as preparation method and preparation thereof

Abstract

The invention relates to the technical field of gel, in particular to nasal protective gel as well as a preparation method and a preparation thereof. The nasal protective gel comprises the following components in percentage by mass: 0.05%-6% of a biomolecule intercalation composite material, 0.04%-30% of an in-situ gel material, 0.01%-34% of an auxiliary material and the balance of water. The nasal protective gel prepared by the invention not only can form a barrier to block bacteria and viruses, but also can directly remove the bacteria and viruses, and secondly, the nasal protective gel can take effect in a short time and also has relatively long effective time due to long residence time and short film forming time.

Description

Technical Field

[0001] The present invention relates to the technical field of gels, and particularly relates to a nasal protective gel, a preparation method thereof, and a preparation. Background Art

[0002] The human nasal cavity is one of the most important olfactory organs, which can not only perceive the external environment, but also play an immune defense role. However, the nasal cavity is easily invaded by foreign harmful substances or allergenic substances, thus causing a series of common diseases, such as nasal congestion, allergic rhinitis, and respiratory tract infections. Nasal congestion may cause ear discomfort, auditory interference, and pronunciation problems, and in severe cases, it may even cause insomnia and sleep apnea. Allergic rhinitis, also known as allergic rhinitis, is a non-infectious nasal mucosal inflammatory disease caused by atopic individuals after contact with allergens. Its main feature is the release of mediators mediated by IgE, mainly histamine, and involves a variety of immune active cells and cytokines. Its occurrence requires three necessary conditions: specific antigen (substance that triggers the body's immune response), atopic individual (individual difference, allergic constitution), and the encounter of specific antigen and atopic individual. Statistical data in recent years have shown that the global prevalence of allergic rhinitis has been increasing year by year. Especially in China, the number of patients with allergic rhinitis is also rising continuously. This not only has a negative impact on the physical and mental health and quality of life of individuals, but also constitutes a certain burden on social economy. Therefore, allergic rhinitis has become a health problem that the general public is concerned about.

[0003] Currently, there are already some preparations for treating nasal congestion and allergic rhinitis on the market, mainly including decongestants, antihistamines, and hormonal drugs. These drugs can relieve the nasal congestion symptoms caused by allergies in the short term, but they are not suitable for long-term use, especially decongestants, because long-term use is likely to lead to abuse by patients, thus causing drug-induced rhinitis. In addition to treating nasal congestion and allergic rhinitis with drugs, the method of cutting off the transmission route can also be adopted. The prior art uses povidone iodine, in-situ gel materials, excipients, and water to prepare a gel preparation. Povidone forms a microcavity carrier and then complexes iodide ions in the cavity of the microcapsule, and exerts a powerful disinfection effect by continuously releasing free iodine. In the aqueous solution state, due to the affinity of povidone for cell membranes, iodine is introduced to the surface of pathogenic bacteria, destroying the cell membranes of pathogenic bacteria and their required nutrients, and then playing a role in quickly killing bacterial spores, fungi, viruses, and some protozoa. However, the retention percentage of the gel prepared by this method at 8 h is between 3.7 - 4.7%, thus resulting in poor defensive effects against viruses, bacteria, etc.

[0004] Therefore, it is necessary to provide a new nasal protective gel preparation and related preparation methods to solve the above problems. Summary of the Invention

[0005] Aiming at the problem that the nasal protective gel in the prior art has a poor defensive effect against viruses and bacteria, the present invention provides a nasal protective gel, a preparation method thereof and a preparation.

[0006] To achieve the above technical purpose, the present invention provides a nasal protective gel, which, by mass percentage, comprises 0.05%-6% of a biomolecule intercalation composite material, 0.04%-30% of an in-situ gel material, 0.01%-34% of an auxiliary material, and the balance is water.

[0007] In an optional embodiment, the preparation raw materials of the biomolecule intercalation composite material include a biomolecule and a carrier material; the biomolecule includes at least one of polysaccharides and proteins; the carrier material includes clay minerals.

[0008] In an optional embodiment, the clay minerals include at least one of bentonite, montmorillonite, laponite, kaolinite, and hydrotalcite-like compounds; the polysaccharides include at least one of chitosan, chitosan oligosaccharide, quaternized chitosan, quaternized chitosan oligosaccharide, β-glucan, and seaweed polysaccharide; the proteins include at least one of mussel adhesive protein and silk fibroin; the mass ratio of the biomolecule to the carrier material is (50-90):(5-50).

[0009] In an optional embodiment, the in-situ gel material includes at least one of a temperature-sensitive gel material, an ion-sensitive gel material, and a pH-sensitive gel material.

[0010] In an optional embodiment, the temperature-sensitive gel material includes at least one of poloxamer 407, poloxamer 188, poly(N-isopropylacrylamide), poly(ethylene oxide)-poly(lactic-co-glycolic acid) copolymer, methylcellulose, and xylan.

[0011] In an alternative embodiment, the temperature-sensitive gel material is poloxamer 407, and based on the mass of the nasal protective gel, the content of poloxamer 407 is 10-30%; or, the temperature-sensitive gel material is poloxamer 188, and based on the mass of the nasal protective gel, the content of poloxamer 188 is 5-30%; or, the temperature-sensitive gel material is poly(N-isopropylacrylamide), and based on the mass of the nasal protective gel, the content of poly(N-isopropylacrylamide) is 20-30%; or, the temperature-sensitive gel material is poly(ethylene glycol)-poly(lactic-co-glycolic acid) copolymer, and based on the mass of the nasal protective gel, the content of poly(ethylene glycol)-poly(lactic-co-glycolic acid) copolymer is 15-30%; or, the temperature-sensitive gel material is methylcellulose, and based on the mass of the nasal protective gel, the content of methylcellulose is 1-10%; or, the temperature-sensitive gel material is xylan, and based on the mass of the nasal protective gel, the content of xylan is 0.1-3%.

[0012] In an alternative embodiment, the ion-sensitive gel material includes at least one of deacetylated gellan gum, sodium alginate, xanthan gum, welan gum, and carrageenan.

[0013] In an alternative embodiment, the ion-sensitive gel material is deacetylated gellan gum, and based on the mass of the nasal protective gel, the content of deacetylated gellan gum is 0.04-3%; or, the ion-sensitive gel material is sodium alginate, and based on the mass of the nasal protective gel, the content of sodium alginate is 0.2-10%; or, the ion-sensitive gel material is xanthan gum, and based on the mass of the nasal protective gel, the content of xanthan gum is 0.1-8%; or, the ion-sensitive gel material is welan gum, and based on the mass of the nasal protective gel, the content of welan gum is 0.1-8%; or, the ion-sensitive gel material is carrageenan, and based on the mass of the nasal protective gel, the content of carrageenan is 0.04-2%.

[0014] In an alternative embodiment, the pH-sensitive gel material includes at least one of cellulose acetate phthalate and carbomer.

[0015] In an alternative embodiment, the pH-sensitive gel material is cellulose acetate phthalate, and based on the mass of the nasal protective gel, the content of cellulose acetate phthalate is 10-30%; or, the pH-sensitive gel material is carbomer, and based on the mass of the nasal protective gel, the content of carbomer is 0.01-0.5%.

[0016] In an alternative embodiment, the adjuvant comprises at least one of an osmotic pressure regulator, a gel regulator, a humectant, and a pH regulator.

[0017] In an alternative embodiment, the osmotic pressure regulator comprises at least one of mannitol, sorbitol, sodium citrate, potassium chloride, and sodium chloride; based on the mass of the nasal protective gel, the content of the osmotic pressure regulator is 0.05-5%; the gel regulator comprises at least one of pectin, hydroxyethyl cellulose, and hydroxypropyl cellulose; based on the mass of the nasal protective gel, the content of the gel regulator is 0.05-1%; the humectant comprises at least one of polyethylene glycol 400, glycerol, propylene glycol, and polysorbate; the pH regulator comprises at least one of sodium hydroxide, triethanolamine, potassium hydroxide, hydrochloric acid, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and dipotassium hydrogen phosphate; the pH of the nasal protective gel is 3.5-8.0.

[0018] In an alternative embodiment, the humectant is glycerol, and based on the mass of the nasal protective gel, the content of glycerol is 3-20%; or, the humectant is propylene glycol, and based on the mass of the nasal protective gel, the content of propylene glycol is 5-20%; or, the humectant is polysorbate, and based on the mass of the nasal protective gel, the content of polysorbate is 0.1-5%; or, the humectant is polyethylene glycol 400, and based on the mass of the nasal protective gel, the content of polyethylene glycol 400 is 5-10%.

[0019] On the other hand, the present invention also provides a method for preparing the nasal protective gel described above, comprising the following steps: Mix the adjuvant, the in-situ gel material, the biomolecule intercalation composite material with water to obtain the nasal protective gel.

[0020] In an alternative embodiment, the method for preparing the biomolecule intercalation composite material comprises: mixing a carrier material, a biomolecule with a solvent, reacting, separating the solid from the liquid, and drying to obtain the biomolecule intercalation composite material.

[0021] In an alternative embodiment, when mixing the carrier material, the biomolecule with the solvent, a surfactant is further added.

[0022] Optionally, the surfactant comprises cetyltrimethylammonium bromide and / or polyvinylpyrrolidone.

[0023] In an alternative embodiment, the solvent is an aqueous oxalic acid solution and / or water, and the mass concentration of the aqueous oxalic acid solution is 0.9-1.2%.

[0024] In an alternative embodiment, the reaction is carried out by at least one of the methods of ultrasound (water bath oscillation), stirring, supercritical fluid environment, and dialysis.

[0025] Optionally, the temperature of the ultrasound is 80 - 85 °C and the time is 2 - 48 h; Optionally, the temperature of the stirring is 20 - 80 °C and the time is 1 - 4 h; Optionally, the temperature in the supercritical fluid environment is 50 - 120 °C, the pressure is 7 - 16 Mpa, and the time is 2 - 12 h; Optionally, the temperature of dialysis is 2 - 8 °C, the time is 2 - 4 days, and the water in the dialysis bag is changed every 2 - 12 h.

[0026] On the other hand, the present invention also provides a preparation, including the nasal protective gel described above, or a nasal protective gel prepared according to the preparation method of the nasal protective gel.

[0027] Optionally, the type of the preparation includes at least one of spray and gel.

[0028] The technical solution of the present invention has the following beneficial effects: 1. A nasal protective gel provided by the present invention, by mass percentage, includes 0.05% - 6% of biomolecule intercalation composite material, 0.04% - 30% of in-situ gel material, 0.01% - 34% of excipients, and the balance is water. The nasal protective gel prepared by the present invention can not only form a barrier to block bacteria and viruses, but also directly scavenge bacteria and viruses. Secondly, due to the long residence time and short film-forming time, it can take effect in a short time and also has a long effective time.

[0029] 2. A nasal protective gel provided by the present invention can effectively prevent external harmful substances, such as viruses, bacteria, dust, etc. from entering the human body through the nasal cavity, thereby reducing the risk of infection and enhancing the preventive effect on diseases such as nasal congestion, allergic rhinitis, and respiratory tract infection. Specifically, this nasal protective gel aims to form a barrier inside the nasal cavity to block external substances from entering the body, and uses the adsorption ability of the carrier material to fix bacteria and viruses on the surface of the nasal protective gel, while using the antibacterial, antiviral or adsorption properties of biomolecules to effectively prevent their transmission. Compared with traditional treatment methods, the nasal protective gel provided by the present invention can quickly form a physical barrier in the nasal cavity. The biomolecule intercalation composite material therein can adsorb bacteria and viruses through electrostatic interaction, and the antibacterial, antiviral or adsorption function of biomolecules can also reduce the risk of infection. This multiple effect can more effectively prevent the spread of the infection source, thereby improving the ability to prevent infection.

[0030] 3. A nasal protective gel provided by the present invention, in which the layer spacing of the biomolecule intercalated composite material is significantly increased, and the overall surface area is significantly improved, thereby significantly enhancing the adsorption effect of the material.

[0031] 4. A nasal protective gel of the present invention has the following effects: (1) Dual antibacterial and antiviral effects: Compared with traditional treatment methods, it realizes the adsorption of bacteria and viruses, and at the same time has antibacterial and antiviral functions, thus improving the ability to prevent infection. (2) Long-lasting antibacterial and antiviral effects: Compared with traditional drug treatments, it can not only quickly relieve symptoms, but also maintain the protective effect for a long time, reducing the risk of re-infection. (3) Safety and usability: The materials of the nasal protective gel are all safe and easily accessible materials. Therefore, the nasal protective gel of the present invention has high safety and usability and can be widely applied to different age groups and populations. (4) High feasibility: The technical solution provided by the present invention has high feasibility. The materials are easy to synthesize and prepare, and the cost is relatively low, and it can be widely applied in the fields of healthcare and hygiene. (5) More comprehensive protection: The nasal protective gel of the present invention can not only be used to prevent diseases such as nasal congestion and allergic rhinitis, but also provide more comprehensive upper respiratory tract protection, which is of great significance especially during the epidemic prevention period. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for the description of the specific embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0033] Figure 1 It is the infrared spectrogram of montmorillonite, chitosan and the montmorillonite biomolecule intercalated composite material obtained in Example 1. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0034] The following embodiments are provided to better understand the present invention further. They are not limited to the best embodiments, and do not limit the content and protection scope of the present invention. Any product obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior art features that is the same as or similar to the present invention falls within the protection scope of the present invention.

[0035] For those steps or conditions not specified in the examples, the operations or conditions of the conventional experimental steps described in the literature in this field can be followed. For the reagents or instruments not specified by the manufacturer, they are all conventional reagent products that can be obtained through commercial purchase.

[0036] Table 1 Material Information

[0037] Example 1 This example provides a method for preparing a biomolecule intercalated composite material, including the following steps: S1. Add 10 g of montmorillonite to 100 g of deionized water, and stir and disperse evenly at a rotation speed of 2500 rpm at room temperature to obtain a first solution.

[0038] S2. Add 70 g of chitosan to 5000 g of an oxalic acid aqueous solution with a mass concentration of 1%, stir at room temperature and a rotation speed of 4000 rpm for 12 h, and after complete dissolution, obtain a second solution.

[0039] S3. Slowly add the first solution to the second solution, perform water bath oscillation at 85 °C for 48 h and then centrifuge. Take the centrifuged precipitate, put it into an oven, dry it at 100 °C for 2 h, take it out, and crush it for standby to obtain a montmorillonite biomolecule intercalated composite material.

[0040] S4. Verification: Detect montmorillonite, chitosan and the montmorillonite biomolecule intercalated composite material by a Fourier transform infrared spectrometer to obtain the infrared spectra of montmorillonite, chitosan and the montmorillonite biomolecule intercalated composite material obtained in Example 1, as Figure 1 shown (montmorillonite is marked as MMT, chitosan is marked as CS, and the montmorillonite biomolecule intercalated composite material obtained in Example 1 is marked as CS / MMT). Figure 1 As can be seen in, in the infrared spectrum of the montmorillonite biomolecule intercalated composite material, there are both the -OH stretching vibration peak of montmorillonite at 1010 cm -1 and the -SiO stretching vibration peak of montmorillonite at 1010 cm -1 , and there are also many characteristic absorption peaks of CS (chitosan), indicating that CS has been inserted into the interlayer of montmorillonite or adsorbed on the surface of montmorillonite. Use an X-ray diffractometer (XRD) to measure and calculate the layer spacing of montmorillonite and the layer spacing of the montmorillonite biomolecule intercalated composite material. The layer spacing of montmorillonite is 1.07 nm, while the layer spacing of the montmorillonite biomolecule intercalated composite material reaches 1.45 nm. From the change of the layer spacing, it can be seen that the addition of chitosan increases the layer spacing of montmorillonite, indicating that chitosan has successfully inserted into the interlayer of montmorillonite, and the montmorillonite biomolecule intercalated composite material has been successfully synthesized.

[0041] Example 2 This example provides a method for preparing a biomolecule intercalated composite material, including the following steps: S1. Add 10 g of bentonite to 120 g of deionized water, and stir until evenly dispersed to obtain a first solution.

[0042] S2. First, add 20 g of cetyltrimethylammonium bromide (CTMAB) and 40 g of hydroxypropyltrimethylammonium chloride chitosan (which belongs to a kind of quaternized chitosan) to the first solution at an interval of 0.5 h to obtain a second solution.

[0043] S3. Stir the second solution in a constant temperature water bath at 80 °C for 2 h, then cool it to room temperature, centrifuge it, take the precipitate after centrifugation and wash it with distilled water, and repeat the steps of centrifugation and washing with distilled water until the pH of the washed water is 7; then place the precipitate in an oven at 105 °C and dry it for 1.5 h, take it out, crush it, and set it aside to obtain a bentonite biomolecule intercalation composite material.

[0044] S4. Verification: Detect bentonite, hydroxypropyltrimethylammonium chloride chitosan, and the bentonite biomolecule intercalation composite material with a Fourier transform infrared spectrometer, compare the spectra. There is a strong broad peak at the position of 3421 cm -1 which is an overlapping absorption peak of the stretching vibrations of N-H and O-H. The absorption peaks at 2920 cm -1 are the symmetric and antisymmetric stretching vibration absorption peaks of -CH3 and -CH2, and the absorption peak at 1475 cm -1 is the bending vibration absorption peak of (CH3)3N + ; in addition, compare the spectra of hydroxypropyltrimethylammonium chloride chitosan and the bentonite biomolecule intercalation composite material. In the spectrum of hydroxypropyltrimethylammonium chloride chitosan, the characteristic peak of the glycosidic bond at 1060 cm -1 overlaps with the stretching vibration peak of Si-O-Si at 1039 cm -1 resulting in a relatively broad absorption peak at 1040 cm -1 in the bentonite biomolecule intercalation composite material. Most of the peaks in the range of 1000 cm -1 - 450 cm -1 in the spectra of the two substances change in area, indicating that the skeletons of the two substances are similar but not the same substance. Furthermore, it shows that hydroxypropyltrimethylammonium chloride chitosan has been successfully modified onto bentonite. Measure and calculate the layer spacing of bentonite and the layer spacing of the bentonite biomolecule intercalation composite material using XRD. The layer spacing of bentonite is 1.78 nm, while the layer spacing value of the bentonite biomolecule intercalation composite material reaches 3.95 nm. From the change in the layer spacing, it can be seen that the addition of hydroxypropyltrimethylammonium chloride chitosan increases the layer spacing of bentonite, meaning that hydroxypropyltrimethylammonium chloride chitosan has successfully inserted into the interlayer of bentonite, and the bentonite biomolecule intercalation composite material has been successfully synthesized.

[0045] Example 3 This example provides a preparation method of a biomolecule intercalation composite material, including the following steps: S1. Add 10 g of montmorillonite to 100 g of deionized water and stir until evenly dispersed to obtain a first solution.

[0046] S2. Add 10 g of cetyltrimethylammonium bromide and 30 g of chitosan oligosaccharide to the first solution successively, with an interval of 0.5 h in between, to obtain a second solution.

[0047] S3. Stir the second solution in a constant temperature water bath at 80 °C for 2 h, then cool it to room temperature, centrifuge, take the precipitate after centrifugation and wash it with distilled water. Repeat the steps of centrifugation and washing with distilled water until the pH of the washed water is 7. Then place the precipitate in an oven at 105 °C and dry it for 1.5 h, take it out, pulverize it, and set it aside to obtain a montmorillonite biomolecule intercalation composite material.

[0048] S4. Verification: Use XRD to measure and calculate the layer spacing of montmorillonite and the montmorillonite biomolecule intercalation composite material. The layer spacing of montmorillonite is 1.03 nm, while the layer spacing of the montmorillonite biomolecule intercalation composite material reaches 1.37 nm. From the change in the layer spacing, it can be seen that the addition of chitosan oligosaccharide increases the layer spacing of montmorillonite, indicating that chitosan oligosaccharide has successfully inserted into the interlayer of montmorillonite, and the montmorillonite biomolecule intercalation composite material has been successfully synthesized.

[0049] Example 4 This example provides a method for preparing a biomolecule intercalation composite material, including the following steps: S1. Add 10 g of montmorillonite to 100 g of deionized water and stir until evenly dispersed to obtain a first solution.

[0050] S2. Add 20 g of cetyltrimethylammonium bromide (CTMAB) and 20 g of quaternized chitosan oligosaccharide to the first solution successively, with an interval of 0.5 h in between, to obtain a second solution.

[0051] S3. Stir the second solution in a constant temperature water bath at 80 °C for 2 h, then cool it to room temperature, centrifuge, take the precipitate after centrifugation and wash it with distilled water. Repeat the steps of centrifugation and washing with distilled water until the pH of the washed water is 7. Then place the precipitate in an oven at 105 °C and dry it for 1.5 h, take it out, pulverize it, and set it aside to obtain a montmorillonite biomolecule intercalation composite material.

[0052] S4. Verification: Use XRD to measure and calculate the layer spacing of montmorillonite and the montmorillonite biomolecule intercalation composite material. The layer spacing of montmorillonite is 1.06 nm, while the layer spacing of the montmorillonite biomolecule intercalation composite material reaches 1.41 nm. From the change in the layer spacing, it can be seen that the addition of quaternized chitosan oligosaccharide increases the layer spacing of montmorillonite, indicating that quaternized chitosan oligosaccharide has successfully adhered to the surface of montmorillonite and inserted into the interlayer of montmorillonite, and the montmorillonite biomolecule intercalation composite material has been successfully synthesized.

[0053] Example 5 This embodiment provides a method for preparing a biomolecule intercalated composite material, comprising the following steps: S1. Add 2 g of hectorite to deionized water to prepare a 2 wt% hectorite colloidal solution, and stir at 1000 rpm until evenly dispersed to obtain a first solution.

[0054] S2. Add 2 g of β-glucan to 80 g of deionized water and stir for 3 h to obtain a second solution.

[0055] S3. Slowly add the first solution to the second solution, stir at 25 °C for 4 h, and centrifuge; take out the precipitate after centrifugation, dry it at 90 °C for 2 h, and set aside to obtain a hectorite biomolecule intercalated composite material.

[0056] S4. Verification: Use XRD to measure and calculate the layer spacing of hectorite and the layer spacing of the hectorite biomolecule intercalated composite material. The layer spacing of hectorite is 1.27 nm, while the layer spacing of the hectorite biomolecule intercalated composite material reaches 1.52 nm. From the change in the layer spacing, it can be seen that the addition of β-glucan increases the layer spacing of hectorite, indicating that β-glucan has successfully inserted into the interlayer of hectorite and adhered to its surface, and the hectorite biomolecule intercalated composite material has been successfully synthesized.

[0057] Example 6 This embodiment provides a method for preparing a biomolecule intercalated composite material, comprising the following steps: S1. Add 10 g of kaolinite to 50 g of deionized water and stir until evenly dispersed to obtain a first solution.

[0058] S2. Add 60 g of algal polysaccharide to 3000 g of deionized water and stir until completely dissolved to obtain a second solution.

[0059] S3. Slowly add the first solution to the second solution, stir at 25 °C for 4 h, and centrifuge; take out the precipitate after centrifugation, dry it at 80 °C for 3 h, and set aside to obtain a kaolinite biomolecule intercalated composite material.

[0060] S4. Verification: Use XRD to measure and calculate the layer spacing of kaolinite and the layer spacing of the kaolinite biomolecule intercalated composite material. The layer spacing of kaolinite is 0.77 nm, while the layer spacing of the kaolinite biomolecule intercalated composite material reaches 1.06 nm. From the change in the layer spacing, it can be seen that the addition of algal polysaccharide increases the layer spacing of kaolinite, indicating that algal polysaccharide has successfully inserted into the interlayer of kaolinite or adsorbed on its surface, and the kaolinite biomolecule intercalated composite material has been successfully synthesized.

[0061] Example 7 This embodiment provides a method for preparing a biomolecule intercalated composite material, comprising the following steps: S1. Add 10 g of hydrotalcite-like material to 150 g of deionized water and stir until evenly dispersed to obtain the first solution.

[0062] S2. Add 90 g of mussel adhesive protein to 500 g of deionized water and stir until completely dissolved to obtain the second solution.

[0063] S3. Add 30 g of polyvinylpyrrolidone to 500 g of deionized water and stir until completely dissolved to obtain the third solution.

[0064] S4. Slowly add the first solution to the third solution and stir at 160 rpm for 3 h to obtain the fourth solution; then slowly add the second solution to the fourth solution, slowly stir at 50 rpm for 4 h, put it into a dialysis bag, and then dialyze in deionized water at 4 °C for 3 days. Change the water every 3 h on the first day, every 6 h on the second day, and every 12 h on the third day. After dialysis, place the material in the dialysis bag in a vacuum drying oven and vacuum dry for five days. After completion, take it out, grind it to obtain the hydrotalcite-like material biomolecule intercalation composite.

[0065] S5. Verification: Use XRD to measure and calculate the layer spacing of the hydrotalcite-like material and the layer spacing of the hydrotalcite-like material biomolecule intercalation composite. The layer spacing of the hydrotalcite-like material is 0.17 nm, while the layer spacing of the hydrotalcite-like material biomolecule intercalation composite reaches 0.31 nm. From the change of the layer spacing, it can be seen that the addition of mussel adhesive protein increases the layer spacing of the hydrotalcite-like material, indicating that mussel adhesive protein has successfully inserted into the interlayer of kaolinite or adsorbed on its surface, and the hydrotalcite-like material biomolecule intercalation composite has been successfully synthesized.

[0066] Example 8 This example provides a preparation method of a biomolecule intercalation composite, including the following steps: S1. Add 10 g of montmorillonite to 100 g of deionized water and stir until evenly dispersed to obtain the first solution.

[0067] S2. Add 50 g of silk fibroin to 300 g of deionized water and stir until completely dissolved to obtain the second solution.

[0068] S3. Add 50 g of polyvinylpyrrolidone to 500 g of deionized water and stir until completely dissolved to obtain the third solution.

[0069] S4. Slowly add the first solution to the third solution, stir at 160 rpm for 3 h to obtain a fourth solution; then slowly add the second solution to the fourth solution, slowly stir at 30 rpm for 6 h, place it in a dialysis bag, and then dialyze in deionized water at 4 °C for 3 days. Change the water every 2 h on the first day, every 4 h on the second day, and every 8 h on the third day. After dialysis, place the material in the dialysis bag in a vacuum drying oven and vacuum dry for five days. After completion, take it out and grind it to obtain a montmorillonite biomolecule intercalation composite material.

[0070] S5. Verification: Use XRD to measure and calculate the layer spacing of montmorillonite and the layer spacing of the montmorillonite biomolecule intercalation composite material. The layer spacing of montmorillonite is 1.06 nm, while the layer spacing of the montmorillonite biomolecule intercalation composite material reaches 1.51 nm. From the change of the layer spacing, it can be seen that the addition of silk fibroin increases the layer spacing of montmorillonite, indicating that silk fibroin has successfully inserted into the interlayer of montmorillonite or adsorbed on its surface, and the montmorillonite biomolecule intercalation composite material has been successfully synthesized.

[0071] Example 9 This example provides a nasal protective gel with the following formula: 3 g of the biomolecule intercalation composite material prepared in Example 1, 0.175 g of an ion-sensitive gel material (xanthan gum), 5 g of a humectant (polysorbate-20), adjust the pH to 6.0 with a pH regulator (triethanolamine), 2 g of an osmotic pressure regulator (sorbitol), and make up to 100 g with deionized water.

[0072] The preparation method includes: according to the above formula, mix the biomolecule intercalation composite material, in-situ gel material, humectant, and osmotic pressure regulator, add water to 90 g, then add a pH regulator to adjust the pH to the target value, and finally add water to make up to 100 g to obtain the nasal protective gel.

[0073] Example 10 This example provides a nasal protective gel with the following formula: 0.05 g of the biomolecule intercalation composite material prepared in Example 2, 0.04 g of an ion-sensitive gel material (carrageenan), 0.1 g of a gel regulator (hydroxypropyl cellulose), 5 g of a humectant (glycerol), adjust the pH to 6.0 with a pH regulator (potassium dihydrogen phosphate), 0.05 g of an osmotic pressure regulator (sodium chloride), and make up to 100 g with deionized water.

[0074] The preparation method includes, according to the above formula, mix the biomolecule intercalation composite material, in-situ gel material, gel regulator, humectant, and osmotic pressure regulator, add water to 90 g, then add a pH regulator to adjust the pH to the target value, and finally add water to make up to 100 g to obtain the nasal protective gel.

[0075] Example 11 This example provides a nasal protective gel with the following formula: 4 g of the biomolecule intercalated composite material prepared in Example 3, 2.5 g of an ion-sensitive gel material (gellan gum), 10 g of a humectant (propylene glycol), the pH is adjusted to 6.0 with a pH regulator (sodium dihydrogen phosphate), 1 g of an osmotic pressure regulator (mannitol), and deionized water is added to make up to 100 g.

[0076] The preparation method is the same as that of Example 9.

[0077] Example 12 This example provides a nasal protective gel with the following formula: 0.5 g of the biomolecule intercalated composite material prepared in Example 4, 0.05 g of an ion-sensitive gel material (deacetylated gellan gum), 5 g of a humectant (propylene glycol), the pH is adjusted to 6.5 with a pH regulator (triethanolamine), 0.8 g of an osmotic pressure regulator (sodium chloride), and deionized water is added to make up to 100 g.

[0078] The preparation method is the same as that of Example 9.

[0079] Example 13 This example provides a nasal protective gel with the following formula: 6 g of the biomolecule intercalated composite material prepared in Example 5, 3 g of an ion-sensitive gel material (sodium alginate), 10 g of a humectant (propylene glycol), the pH is adjusted to 8.0 with a pH regulator (triethanolamine), 1 g of an osmotic pressure regulator (potassium chloride), and deionized water is added to make up to 100 g.

[0080] The preparation method is the same as that of Example 9.

[0081] Example 14 This example provides a nasal protective gel with the following formula: 5 g of the biomolecule intercalated composite material prepared in Example 6, 1.75 g of an ion-sensitive gel material (carrageenan), 0.05 g of a gel regulator (hydroxyethyl cellulose), 8 g of a humectant (glycerol), the pH is adjusted to 7.0 with a pH regulator (triethanolamine), 0.5 g of an osmotic pressure regulator (potassium chloride), and deionized water is added to make up to 100 g.

[0082] The preparation method is the same as that of Example 10.

[0083] Example 15 This example provides a nasal protective gel with the following formula: 2 g of the biomolecule intercalated composite material prepared in Example 7, 0.5 g of an ion-sensitive gel material (sodium alginate), 1 g of a gel regulator (pectin), 10 g of a humectant (propylene glycol), the pH was adjusted to 6.0 with a pH regulator (sodium dihydrogen phosphate), 1 g of an osmotic pressure regulator (sodium chloride), and deionized water was added to make up to 100 g.

[0084] The preparation method was the same as that of Example 10.

[0085] Example 16 This example provides a nasal protective gel with the following formula: 3.5 g of the biomolecule intercalated composite material prepared in Example 8, 0.225 g of an ion-sensitive gel material (carrageenan), 0.5 g of a gel regulator (pectin), 3 g of a humectant (glycerol), the pH was adjusted to 6.5 with a pH regulator (sodium dihydrogen phosphate), 2 g of an osmotic pressure regulator (mannitol), and deionized water was added to make up to 100 g.

[0086] The preparation method was the same as that of Example 10.

[0087] Example 17 This example provides a nasal protective gel with the following formula: 5 g of the biomolecule intercalated composite material prepared in Example 1, 30 g of a pH-sensitive gel material (cellulose acetate phthalate), 12 g of a humectant (propylene glycol), the pH was adjusted to 8.0 with a pH regulator (triethanolamine), 1.5 g of an osmotic pressure regulator (sodium chloride), and deionized water was added to make up to 100 g.

[0088] The preparation method was the same as that of Example 9.

[0089] Example 18 This example provides a nasal protective gel with the following formula: 0.1 g of the biomolecule intercalated composite material prepared in Example 2, 15 g of a pH-sensitive gel material (cellulose acetate phthalate), 0.8 g of a gel regulator (pectin), 10 g of a humectant (propylene glycol), the pH was adjusted to 5.5 with a pH regulator (sodium dihydrogen phosphate), 1 g of an osmotic pressure regulator (sodium chloride), and deionized water was added to make up to 100 g.

[0090] The preparation method was the same as that of Example 10.

[0091] Example 19 This example provides a nasal protective gel with the following formula: 2 g of the biomolecule intercalated composite material prepared in Example 3, 0.3 g of pH-sensitive gel material (carbomer 934), 0.05 g of gel regulator (hydroxyethyl cellulose), 20 g of humectant (glycerol), pH adjusted to 7.5 with pH regulator (triethanolamine), 0.5 g of osmotic pressure regulator (potassium chloride), and deionized water was added to make up to 100 g.

[0092] The preparation method was the same as that in Example 10.

[0093] Example 20 This example provides a nasal protective gel with the following formula: 3 g of the biomolecule intercalated composite material prepared in Example 4, 0.175 g of pH-sensitive gel material (carbomer 934), 4 g of humectant (glycerol), pH adjusted to 6.5 with pH regulator (triethanolamine), 2 g of osmotic pressure regulator (sorbitol), and deionized water was added to make up to 100 g.

[0094] The preparation method was the same as that in Example 9.

[0095] Example 21 This example provides a nasal protective gel with the following formula: 5.5 g of the biomolecule intercalated composite material prepared in Example 5, 0.1 g of pH-sensitive gel material (carbomer 940), 5 g of humectant (propylene glycol), pH adjusted to 6.5 with pH regulator (triethanolamine), 0.7 g of osmotic pressure regulator (mannitol), and deionized water was added to make up to 100 g.

[0096] The preparation method was the same as that in Example 9.

[0097] Example 22 This example provides a nasal protective gel with the following formula: 4 g of the biomolecule intercalated composite material prepared in Example 6, 0.225 g of pH-sensitive gel material (carbomer U21), 1 g of gel regulator (pectin), 8 g of humectant (glycerol), pH adjusted to 6.5 with pH regulator (sodium dihydrogen phosphate), 2 g of osmotic pressure regulator (mannitol), and deionized water was added to make up to 100 g.

[0098] The preparation method was the same as that in Example 10.

[0099] Example 23 This example provides a nasal protective gel with the following formula: 1 g of the biomolecule intercalated composite material prepared in Example 7, 20 g of pH-sensitive gel material (cellulose acetate phthalate), 8 g of humectant (propylene glycol), pH adjusted to 6.0 with pH regulator (sodium dihydrogen phosphate), 1 g of osmotic pressure regulator (sodium chloride), and deionized water was added to make up to 100 g.

[0100] The preparation method is the same as that of Example 9.

[0101] Example 24 This example provides a nasal protective gel with the following formula: 6 g of the biomolecule intercalated composite material prepared in Example 8, 10 g of a pH-sensitive gel material (cellulose acetate phthalate), 0.2 g of a gel regulator (hydroxypropyl cellulose), 5 g of a humectant (glycerol), the pH is adjusted to 5.0 with a pH regulator (potassium dihydrogen phosphate), 0.9 g of an osmotic pressure regulator (sodium chloride), and deionized water is added to make up to 100 g.

[0102] The preparation method is the same as that of Example 10.

[0103] Example 25 This example provides a nasal protective gel with the following formula: 3 g of the biomolecule intercalated composite material prepared in Example 1, 20 g of a temperature-sensitive gel material (polyethylene glycol - poly(lactic-co-glycolic acid) copolymer), 5 g of a humectant (polysorbate-20), the pH is adjusted to 7.5 with a pH regulator (triethanolamine), 2 g of an osmotic pressure regulator (sorbitol), and deionized water is added to make up to 100 g.

[0104] The preparation method is the same as that of Example 9.

[0105] Example 26 This example provides a nasal protective gel with the following formula: 1 g of the biomolecule intercalated composite material prepared in Example 2, 20 g of a temperature-sensitive gel material (poloxamer 407), 0.05 g of a gel regulator (hydroxymethyl cellulose), 15 g of a humectant (glycerol), the pH is adjusted to 7.0 with a pH regulator (triethanolamine), 0.5 g of an osmotic pressure regulator (sodium chloride), and deionized water is added to make up to 100 g.

[0106] The preparation method is the same as that of Example 10.

[0107] Example 27 This example provides a nasal protective gel with the following formula: 6 g of the biomolecule intercalated composite material prepared in Example 3, 10 g of a temperature-sensitive gel material (poloxamer 407), 0.1 g of a gel regulator (hydroxypropyl cellulose), 5 g of a humectant (glycerol), the pH is adjusted to 6.0 with a pH regulator (potassium dihydrogen phosphate), 0.5 g of an osmotic pressure regulator (sodium chloride), and deionized water is added to make up to 100 g.

[0108] The preparation method is the same as that of Example 10.

[0109] Example 28 This embodiment provides a nasal protective gel with the following formula: 4 g of the biomolecule intercalated composite material prepared in Example 4, 20 g of a temperature-sensitive gel material (poly(N-isopropylacrylamide)), 1 g of a gel regulator (pectin), 10 g of a humectant (propylene glycol), the pH is adjusted to 6.0 with a pH regulator (sodium dihydrogen phosphate), 1 g of an osmotic pressure regulator (potassium chloride), and deionized water is added to make up to 100 g.

[0110] The preparation method is the same as that of Example 10.

[0111] Example 29 This embodiment provides a nasal protective gel with the following formula: 2.5 g of the biomolecule intercalated composite material prepared in Example 5, 5 g of a temperature-sensitive gel material (poloxamer 188), 15 g of a humectant (propylene glycol), the pH is adjusted to 6.5 with a pH regulator (triethanolamine), 0.8 g of an osmotic pressure regulator (sodium chloride), and deionized water is added to make up to 100 g.

[0112] The preparation method is the same as that of Example 9.

[0113] Example 30 This embodiment provides a nasal protective gel with the following formula: 2 g of the biomolecule intercalated composite material prepared in Example 6, 3 g of a temperature-sensitive gel material (methylcellulose), 0.5 g of a gel regulator (pectin), 10 g of a humectant (glycerol), the pH is adjusted to 6.5 with a pH regulator (sodium dihydrogen phosphate), 2.0 g of an osmotic pressure regulator (mannitol), and deionized water is added to make up to 100 g.

[0114] The preparation method is the same as that of Example 10.

[0115] Example 31 This embodiment provides a nasal protective gel with the following formula: 5.5 g of the biomolecule intercalated composite material prepared in Example 7, 0.5 g of a temperature-sensitive gel material (xylan), 20 g of a humectant (propylene glycol), the pH is adjusted to 6.0 with a pH regulator (sodium dihydrogen phosphate), 1 g of an osmotic pressure regulator (potassium chloride), and deionized water is added to make up to 100 g.

[0116] The preparation method is the same as that of Example 9.

[0117] Example 32 This embodiment provides a nasal protective gel with the following formula: 0.05 g of the biomolecule intercalated composite material prepared in Example 8, 25 g of the temperature-sensitive gel material (poloxamer 188), 15 g of the humectant (propylene glycol), the pH was adjusted to 8.0 with the pH regulator (triethanolamine), 1 g of the osmotic pressure regulator (mannitol), and deionized water was added to make up to 100 g.

[0118] The preparation method is the same as that of Example 9.

[0119] Example 33 This example provides a nasal protective gel with the following formula: 0.05 g of the biomolecule intercalated composite material prepared in Example 8, 0.225 g of the ion-sensitive gel material (carrageenan), 0.5 g of the gel regulator (pectin), 3 g of the humectant (glycerol), the pH was adjusted to 6.5 with the pH regulator (sodium dihydrogen phosphate), 2.0 g of the osmotic pressure regulator (mannitol), and deionized water was added to make up to 100 g.

[0120] The preparation method is the same as that of Example 10.

[0121] Example 34 This example provides a nasal protective gel. The formula and preparation method are basically the same as those of Example 33, except that "0.05 g of the biomolecule intercalated composite material" is replaced by "0.2 g of the biomolecule intercalated composite material".

[0122] The preparation method is the same as that of Example 10.

[0123] Example 35 This example provides a nasal protective gel. The formula and preparation method are basically the same as those of Example 33, except that "0.05 g of the biomolecule intercalated composite material" is replaced by "1 g of the biomolecule intercalated composite material".

[0124] The preparation method is the same as that of Example 10.

[0125] Example 36 This example provides a nasal protective gel. The formula and preparation method are basically the same as those of Example 33, except that "0.05 g of the biomolecule intercalated composite material" is replaced by "2 g of the biomolecule intercalated composite material".

[0126] The preparation method is the same as that of Example 10.

[0127] Example 37 This example provides a nasal protective gel. The formula and preparation method are basically the same as those of Example 33, except that "0.05 g of the biomolecule intercalated composite material" is replaced by "4 g of the biomolecule intercalated composite material".

[0128] The preparation method is the same as that of Example 10.

[0129] Example 38 This example provides a nasal protective gel. The formulation and preparation method are basically the same as those in Example 33, except that "0.05 g of biomolecule intercalated composite material" is replaced with "6 g of biomolecule intercalated composite material".

[0130] The preparation method is the same as that in Example 10.

[0131] Comparative Example 1 This comparative example provides a nasal protective gel with the following formulation: 3 g of the biomolecule intercalated composite material prepared in Example 1, the pH is adjusted to 5.5 with a pH regulator (potassium dihydrogen phosphate), 1.0 g of an osmotic pressure regulator (sodium chloride), and deionized water is added to make up to 100 g.

[0132] The preparation method includes: according to the above formulation, the biomolecule intercalated composite material and the osmotic pressure regulator are mixed, water is added to 90 g, then the pH regulator is added to adjust the pH to the target value, and finally water is added to make up to 100 g to obtain the nasal protective gel.

[0133] Comparative Example 2 This comparative example provides a nasal protective gel with the following formulation: 1 g of chitosan, 0.2 g of an ion-sensitive gel material (xanthan gum), 0.2 g of a gel regulator (hydroxypropyl cellulose), 10 g of a humectant (propylene glycol), the pH is adjusted to 6.5 with a pH regulator (triethanolamine), 0.5 g of an osmotic pressure regulator (potassium chloride), and deionized water is added to make up to 100 g.

[0134] The preparation method includes, according to the above formulation, chitosan, an in-situ gel material, a gel regulator, an osmotic pressure regulator, and a humectant are mixed, water is added to 90 g, then the pH regulator is added to adjust the pH to the target value, and finally water is added to make up to 100 g to obtain the nasal protective gel.

[0135] Comparative Example 3 This comparative example provides a nasal protective gel with the following formulation: 1.25 g of montmorillonite, 0.1 g of an ion-sensitive gel material (carrageenan), 8 g of a humectant (glycerol), the pH is adjusted to 6.0 with a pH regulator (sodium dihydrogen phosphate), 2 g of an osmotic pressure regulator (sorbitol), and deionized water is added to make up to 100 g.

[0136] The preparation method includes: according to the above formulation, montmorillonite, an in-situ gel material, an osmotic pressure regulator, and a humectant are mixed, water is added to 90 g, then the pH regulator is added to adjust the pH to the target value, and finally water is added to make up to 100 g to obtain the nasal protective gel.

[0137] Comparative Example 4 This comparative example provides a nasal protective gel with the following formula: 1 g of chitosan, 1 g of montmorillonite, 0.175 g of ion-sensitive gel material (carrageenan), 4 g of humectant (glycerol), pH adjusted to 6.0 with pH regulator (triethanolamine), 1 g of osmotic pressure regulator (sodium chloride), and deionized water added to make up to 100 g.

[0138] The preparation method includes: according to the above formula, mixing chitosan, montmorillonite, in-situ gel material, osmotic pressure regulator and humectant, adding water to 90 g, then adding pH regulator to adjust the pH to the target value, and finally adding water to make up to 100 g to obtain the nasal protective gel.

[0139] Comparative Example 5 This comparative example provides a nasal protective gel with the following formula: 0.25 g of pH-sensitive gel material (carbomer 940), 0.2 g of gel regulator (hydroxypropyl cellulose), 15 g of humectant (propylene glycol), pH adjusted to 7.0 with pH regulator (triethanolamine), 0.5 g of osmotic pressure regulator (potassium chloride), and deionized water added to make up to 100 g.

[0140] The preparation method includes, according to the above formula, mixing in-situ gel material, gel regulator, osmotic pressure regulator and humectant, adding water to 90 g, then adding pH regulator to adjust the pH to the target value, and finally adding water to make up to 100 g to obtain the nasal protective gel.

[0141] Comparative Example 6 This comparative example provides a nasal protective gel with the following formula: 1 g of chitosan, 1 g of montmorillonite, 8 g of humectant (glycerol), pH adjusted to 6.0 with pH regulator (sodium dihydrogen phosphate), 2 g of osmotic pressure regulator (sorbitol), and deionized water added to make up to 100 g.

[0142] The preparation method includes, according to the above formula, mixing chitosan, montmorillonite, osmotic pressure regulator and humectant, adding water to 90 g, then adding pH regulator to adjust the pH to the target value, and finally adding water to make up to 100 g to obtain the nasal protective gel.

[0143] Comparative Example 7 This comparative example provides a nasal protective gel, the formula and preparation method are basically the same as those in Example 33, the only difference is that "0.05 g of biomolecule intercalated composite material" is replaced by "0.01 g of biomolecule intercalated composite material".

[0144] The preparation method is the same as that in Example 10.

[0145] Comparative Example 8 This comparative example provides a nasal protective gel, whose formulation and preparation method are basically the same as those of Example 33, except that "0.05 g of biomolecule intercalated composite material" is replaced with "0.04 g of biomolecule intercalated composite material".

[0146] The preparation method is the same as that of Example 10.

[0147] Comparative Example 9 This comparative example provides a nasal protective gel, whose formulation and preparation method are basically the same as those of Example 33, except that "0.05 g of biomolecule intercalated composite material" is replaced with "8 g of biomolecule intercalated composite material".

[0148] The preparation method is the same as that of Example 10.

[0149] Comparative Example 10 This comparative example provides a nasal protective gel, whose formulation and preparation method are basically the same as those of Example 33, except that "0.05 g of biomolecule intercalated composite material" is replaced with "10 g of biomolecule intercalated composite material".

[0150] The preparation method is the same as that of Example 10.

[0151] Experimental Example 1 The layer spacing of the carrier material before intercalation and the biomolecule intercalated composite material after intercalation in Examples 1 - 8 was statistically analyzed. The results are shown in Table 2. The layer spacing of the biomolecule intercalated composite materials prepared in Examples 1 - 8 was greatly increased, and the growth ratio was between 20% - 122%.

[0152] Table 2 Layer Spacing Results

[0153] Experimental Example 2 Shear viscosity tests were performed on the nasal protective gels prepared in Examples 17 - 24, Comparative Examples 1, 2, 4, 6, and the commercially available Bentrio. At the same time, the above samples were respectively mixed with artificial nasal fluid at a ratio of 1:1 (v / v) (wherein, the artificial nasal fluid was prepared as follows: 1.975 g of sodium chloride, 20.64 g of calcium chloride, and 0.92 g of potassium chloride were respectively weighed and dissolved in an appropriate amount of purified water. After adjusting the pH to 6.4, the volume was made up to 250 mL with purified water), and the shear viscosity tests were performed on the mixed samples respectively.

[0154] The method for the shear viscosity test is as follows: Turn on the rotational rheometer, install the 20 - mm upper plate, click the run sequence, set the test temperature to 25 °C, the test gap to 0.5 mm, the starting shear rate to 0.001 s -1 and the ending shear rate to 100 s -1, the number of sampling points between each order of magnitude is 10; click to load the sample when the temperature reaches 25 °C, and click to start the current sequence after placing the sample on the plate.

[0155] The measurement results are shown in Table 3 below. The viscosities of Examples 17 - 24 and Comparative Examples 1, 2, 4, and 6 before mixing with artificial nasal fluid are between 300 - 500 mPa·s, and they can be administered by nasal spray pump. However, the viscosity of commercially available Bentrio reaches 947 mPa·s, approaching 1000 mPa·s, with a relatively high viscosity. It is very difficult to spray out if administered by nasal spray pump. The gel viscosities of Examples 17 - 24 after mixing with artificial nasal fluid are between 1629 - 1776 mPa·s, showing good retention ability in the nasal cavity. The gel viscosities of Comparative Examples 1, 2, 4, and 6 after mixing with artificial nasal fluid are between 1321 - 1482 mPa·s, and their nasal retention ability is poorer than that of Examples 17 - 24. The viscosity of commercially available Bentrio after mixing with artificial nasal fluid is only 1147 mPa·s, and its adhesion ability in the nasal cavity is weaker compared with the examples and comparative examples.

[0156] Table 3 Measurement Results

[0157] Experimental Example 3 The methylene blue adsorption performance tests were carried out on the biomolecule intercalated composites prepared in Example 1, Examples 7 - 8, and the mixture of chitosan and montmorillonite in Comparative Example 4 (the mass ratio of chitosan to montmorillonite is 1:1).

[0158] Method: Take 1 g of each example / comparative example and add it to a 1000 mg / L methylene blue solution, adjust the pH to 6.4, and the temperature to 36 °C.

[0159] The measurement results are shown in Table 4. The adsorption amounts of Example 1, Examples 7 - 8 tend to be stable at about 6 h, and the stable adsorption amounts are between 114.1 mg / g - 122.4 mg / g, and do not decrease significantly at 10 h. The adsorption amounts at 10 h are between 111.3 mg / g - 122.7 mg / g. The adsorption amount of Comparative Example 4 approaches stability at 4 h, with an adsorption amount of 50.3 mg / g, and the adsorption amount at 8 h has started to decrease significantly. It shows that the biomolecule intercalated composites prepared in this application have better adsorption amounts and long-lasting effects.

[0160] Table 4 Measurement Results - Adsorption Amount

[0161] Experimental Example 4 Retention tests in the nasal cavity were conducted on the gels prepared in Examples 15 - 16, Example 25, and Comparative Examples 1 - 6, and the commercially available preparation Bentrio. Method: A fluorescent agent was added to the gel, and then it was filled into a spray bottle. The gel was sprayed into the nasal cavity of a single nostril of a rat in vivo, and the retention amount of the gel in the nasal cavity was determined by visually observing whether the fluorescence was visible. One rat was used in each group, and each group was tested 3 times, and the results were averaged.

[0162] The measurement results are shown in Table 5. The retention ability of the gels in Examples 15, 16, and 25 in the nasal cavity was significantly higher than that of the gels in Comparative Examples 1 - 6. After the gels in Comparative Examples 1 - 6 formed a film in the nasal cavity, due to the fluidity of the gels, they were quickly cleared by the nasal ciliary movement. Five minutes after the gel formed a film, the retention percentages were 38.3%, 27.9%, 59.6%, 70.4%, 63.9%, and 15.3% respectively; while for the commercially available product Bentrio and the gels in Examples 15, 16, and 25, because they could quickly gel and adhere to the nasal mucosa after reaching the film-forming site, 60 minutes after the film formed, the retention percentages in the nasal cavity were 42.5%, 57.3%, 55.8%, and 43.1% respectively. The gels in Examples 15, 16, and 25 were beneficial to increasing the retention time of the gel in the nasal cavity. The retention time was up to 10 hours, significantly higher than that of the commercially available product Bentrio (4 hours), providing an opportunity for the gel to be fully absorbed and transported, and could overcome the gravitational effect in the upright state of the human body, prevent nasal ciliary movement, and increase the retention time in the nasal cavity. The retention percentage of the gels prepared in Examples 15 - 16 was better because, due to the self-characteristics of proteins, it could additionally increase the film-forming property and adhesiveness of the gel.

[0163] Table 5 Measurement Results - Retention Percentage

[0164] Experimental Example 5 The bactericidal effects of the gels prepared in Examples 10, 15 - 18, 20, 25, 27, 29, 32 and Comparative Examples 1 - 6, and the commercially available Bentrio were determined.

[0165] Test strains: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, all provided by the Food Safety Culture Collection Center of the Guangdong Food Microbiology Safety Engineering Technology Research and Development Center; Culture medium: Tryptone Soy Agar Medium (TSA): 15 g of tryptone, 50 g of soy peptone, 5 g of sodium chloride, 16 g of agar, 1 L of water, pH 7.2 ± 0.2, autoclaved at 121 °C for 20 min; Neutralizing agent: 10 g of sodium thiosulfate + 2 g of Tween-80 + 1000 mL of PBS (phosphate buffer solution); Organic interfering substance: Bovine serum albumin solution with a mass fraction of 3% (prepared by dissolving BSA (bovine serum albumin) powder in deionized water); Main instruments and tools: Steam sterilizer, laminar flow hood, constant temperature incubator, petri dishes, glass bottles, graduated cylinders, pipettes; Method: Bacterial quantitative killing test according to the "Disinfection Technical Specification"; (1) Prepare tryptic soy agar medium (TSA), normal saline, neutralizing agent, and purified water, and then place them together with petri dishes and pipette tips in the sterilizer and sterilize at 121 °C for 20 min. After completion, take them out and place them in the laminar flow hood for standby (the medium is placed in a water bath at 42 ± 3 °C); (2) Prepare the test bacterial suspension with a concentration of 1×10 8 cfu / ml to 5×10 8 cfu / ml; (3) Take a sterile test tube for disinfection test, first add 0.5 ml of the test bacterial suspension, then add 0.5 ml of the organic interfering substance, mix well, place it in a 20 °C water bath for 5 min, and then use a sterile pipette to suck 4.0 ml of the gel and inject it into it, mix quickly and start timing immediately; (4) After the test bacterial suspension and the gel interact with each other for 0.5 min, 1.0 min, and 1.5 min respectively, suck 0.5 ml of the mixed solution of the test bacterial suspension and the gel and add it to 4.5 ml of the sterilized neutralizing agent, and mix well; (5) After the mixed solution of the test bacterial suspension and the gel in each tube is treated with the neutralizing agent for 10 min, respectively suck 1.0 ml of the sample solution, add it to the sterilized petri dish, and then add 15 ml of the medium, shake well, and incubate in an inverted position in a constant temperature incubator at 37 °C for 48 h; (6) At the same time, use normal saline to replace the gel and conduct a parallel test as a positive control; After the culture is completed, count and convert the technical results to the logarithm with base 10, that is, the killing logarithm value.

[0166] The results are shown in Table 6 - Table 23. The commercially available Bentrio and Comparative Examples 1 - 6 have poor killing effects on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with the killing logarithm value < 5; Examples 10, 15 - 18, 20, 25, 27, 29, and 32 have obvious inhibitory effects on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with the killing logarithm value > 5.

[0167] Table 6 Results - Positive control group

[0168] Table 7 Experimental Results - Example 10

[0169] Table 8 Experimental Results - Example 15

[0170] Table 9 Experimental Results - Example 16

[0171] Table 10 Experimental Results - Example 17

[0172] Table 11 Experimental Results - Example 18

[0173] Table 12 Experimental Results - Example 20

[0174] Table 13 Experimental Results - Example 25

[0175] Table 14 Experimental Results - Example 27

[0176] Table 15 Experimental Results - Example 29

[0177] Table 16 Experimental Results - Example 32

[0178] Table 17 Experimental Results - Commercially Available Bentrio

[0179] Table 18 Experimental Results - Comparative Example 1

[0180] Table 19 Experimental Results - Comparative Example 2

[0181] Table 20 Experimental Results - Comparative Example 3

[0182] Table 21 Experimental Results - Comparative Example 4

[0183] Table 22 Experimental Results - Comparative Example 5

[0184] Table 23 Experimental Results - Comparative Example 6

[0185] Experimental Example 6 A complete skin irritation test was conducted on the gels prepared in Example 9, Example 12, Example 19, Example 28, Example 30, Comparative Example 1 - Comparative Example 2, Comparative Example 6 and commercially available Bentrio.

[0186] Test samples: gels prepared in Example 9, Example 12, Example 19, Example 28, Example 30, Comparative Example 1 - Comparative Example 2, Comparative Example 6 and commercially available Bentrio; Test animals: ordinary New Zealand rabbits, 3 in each group, body weight range: 2.0 kg - 2.5 kg; Test method: "Disinfection Technical Specification" 2002 edition, Part 2, 2.3.3 Skin Irritation Test; Test conditions: environmental temperature 23°C ± 3°C, relative humidity 55% ± 15%; Test procedure: Before the test, the hair on both sides of the spine of the rabbits was shaved off, and the hair removal area was about 3 cm × 3 cm on the left and right sides respectively. The next day, 0.5 mL of the test sample was directly applied to one side of the skin, covered with a layer of non-irritating plastic film, and then fixed with non-irritating adhesive tape. The skin on the other side was used as a blank control. The closed test was adopted, and the application time was 4 h. After the experiment, the residual sample was removed with warm water; Result evaluation: The skin reaction results of the test sites were observed at 1 h, 24 h and 48 h after removing the sample. The skin reaction was scored according to the skin irritation reaction scoring table. According to the highest integral mean value at each observation point of 1 h, 24 h and 48 h, the skin irritation intensity was determined according to the scoring criteria of skin irritation reaction in Table 2 - 11 and the skin irritation intensity classification in Table 2 - 12 of the "Disinfection Technical Specification" 2002 edition, 2.3.3 Skin Irritation Test section. The scores of 3 animals were added up at each time point and divided by the number of animals to obtain the skin irritation reaction integral mean value (irritation index) at different time points. The test results are shown in Table 24. The results of the complete skin irritation test of commercially available Bentrio, Comparative Example 1, Comparative Example 2, Comparative Example 6 and the gels of Example 9, Example 12, Example 19, Example 28, Example 30 were all non-irritating, showing that the scoring results were all 0.

[0187] Table 24 Statistical Results / points

[0188] Experimental Example 7 Multiple complete skin irritation tests were conducted on the gels prepared in Example 10, Example 15, Example 20, Example 26, Example 31 and Comparative Examples 3 - 5, and commercially available Bentrio.

[0189] Test samples: Gels prepared in Example 10, Example 15, Example 20, Example 26, Example 31 and Comparative Examples 3 - 5, commercially available Bentrio; Test animals: Ordinary New Zealand rabbits, 3 in each group, body weight range: 2.0 kg - 2.5 kg; Test method and evaluation: "Disinfection Technical Specification" 2002 edition, Part 2, 2.3.3 Skin Irritation Test; Test conditions: Ambient temperature 23°C ± 3°C, relative humidity 55% ± 15%; Test procedure: 24 hours before the test, remove the hair on both sides of the spine on the back of the New Zealand rabbit with a depilatory agent, without damaging the skin. The hair removal area is about 3 cm × 3 cm on the left and right respectively. The next day, apply 0.5 mL of the test sample on the left skin, and the right skin is used as a blank control. After 4 hours of application, wash with water to remove the residue. Apply once a day for 14 consecutive days. Observe the results 24 hours after each application. According to the scoring criteria for skin irritation reaction in Table 2 - 11 and the skin irritation intensity classification in Table 2 - 12 of the "Disinfection Technical Specification" 2002 edition, 2.3.3 Skin Irritation Test section, score the erythema and edema formation on the animal skin. In order to facilitate the application of the test substance and the observation of the results, hair should be cut if necessary. The treatment method of the control area is the same as that of the test area; Evaluation regulations: Calculate the average score (irritation index) per animal per day according to the following formula, and evaluate the level of skin irritation intensity of the test substance to the animal skin according to the skin irritation intensity classification standard table.

[0190] Average score per animal per day = ∑(total score of erythema or edema of each animal on the Nth day) / (number of test animals × N).

[0191] The test results are shown in Table 25. The commercially available Bentrio and Comparative Examples 3 - 5 and the gels prepared in Example 10, Example 15, Example 20, Example 26, Example 31 were non - irritating in the multiple complete skin irritation test on New Zealand rabbits. The scoring results were all 0, meeting the requirements of the "Disinfection Technical Specification" (2002 edition).

[0192] Table 25 Statistical results / points

[0193] Experimental Example 8 For the gels prepared in Example 9, Example 11, Example 13, Example 22 and Comparative Examples 1 - 6, a commercially available Bentrio was subjected to an acute oral toxicity test.

[0194] Test samples: gels prepared in Example 9, Example 11, Example 13, Example 22 and Comparative Examples 1 - 6, commercially available Bentrio; Animal species and strain: SPF - level KM mice; 110 males and 110 females, body weight range 18g - 22g; Test method: "Disinfection Technical Specification" 2002 edition, Part 2, 2.3.1 Acute oral toxicity test; Dose level: single - limit method, that is, 220 animals were orally administered at 5000 mg / kg (dose / body weight); Test procedure: Before the test, the experimental animals were fasted overnight without restricting water intake; during the test, the body weights of the animals were weighed, randomly grouped, and gavaged orally once. The gavage volume each time was 0.2 ml / 10 g body weight. After gavage, they were fasted for another 3 h and then given normal diet; after exposure, a separate and comprehensive record was made for each animal, and the poisoning manifestations and death conditions of the experimental animals were observed. Then, a careful examination was carried out once a day. The body weights were measured on the first day D0, the seventh day D7, and the fourteenth day D14 after gavage, and the observation period was 14 days.

[0195] Result evaluation: The test statistical results are shown in Table 26. It can be seen from the table that the commercially available Bentrio, the gels prepared in Example 9, Example 11, Example 13, Example 22 and Comparative Examples 1 - 6 did not cause animal death during the experiment. Therefore, the acute oral toxicity LD50 of the above - mentioned gels for SPF - level KM mice is > 5000 mg / kg. According to the evaluation regulations, the above - mentioned gels are all actually non - toxic.

[0196] Table 26 Statistical results

[0197] Note: No obvious poisoning symptoms or death were observed in all test animals during the 14 - day observation period.

[0198] Experimental Example 9 For the gels prepared in Example 12, Example 14, Example 24 and Comparative Examples 1, 3, 6, a commercially available Bentrio was subjected to an acute eye irritation test.

[0199] Test samples: gels prepared in Example 12, Example 14, Example 24 and Comparative Examples 1, 3, 6, commercially available Bentrio; Test animals: ordinary - grade animal house, experimental animal use license number: SYXK(Guangdong)2016 - 0156; Animal species and strain: Ordinary New Zealand rabbits; 28 females; Body weight range: 2.0 kg - 2.2 kg; Animal certificate number: 44007600007442; Animal source: The experimental animals were provided by Huadong Experimental Animal Farm in Huadong, Huadu District, Guangzhou City (Production license number of experimental animals: SCXK (Guangdong) 2019 - 0023); Inspection method: "Disinfection Technical Specification" 2002 edition, Part 2, 2.3.4 Acute eye irritation test; Detection conditions: Ambient temperature 24°C ± 2°C, relative humidity 55% ± 15%; Test procedure: 24 hours before the test, conduct a routine examination on the two eyes of the experimental animals. During the test, drop 0.1 mL of the test sample into the conjunctival sac, passively close the eyes for 4 s to prevent the loss of the test sample, and rinse with physiological saline after 30 s. Use physiological saline as the normal control on the other side. Check the eyes at 1 h, 24 h, 48 h, and 72 h after the end of the test. At the same time, in order to avoid insufficient action of the sample in the short term, observe the eyes again 21 days after the end of the test. When observing, use 2% sodium fluorescein solution to check the changes in the cornea and iris, and record the integral according to the scoring standard of the acute eye irritation reaction of rabbits in each inspection.

[0200] Result evaluation: Score the acute irritation reactions of the rabbit cornea, iris, and conjunctiva, and calculate the scores of each group at different observation times (24 h, 48 h, and 72 h) respectively. Calculate the average score of each animal in the four aspects of corneal damage, iris damage, conjunctival congestion, and conjunctival edema at three different observation times (the sum of the scores of 24 h, 48 h, and 72 h of each animal divided by the number of observations 3). Determine the irritation intensity of the test sample on the eyes according to the scoring standard of the acute eye irritation reaction of rabbits.

[0201] The test results are shown in Table 27. The gels prepared in Example 12, Example 16, Example 24, and Comparative Example 1, Comparative Example 3, and Comparative Example 6, and the commercially available Bentrio are non - irritating to the eyes of New Zealand rabbits, and the average score results of corneal damage, iris damage, conjunctival bleeding, and conjunctival edema are 0, meeting the requirements of the "Disinfection Technical Specification" (2002 edition).

[0202] At the same time, it was observed that 21 days after the end of the test, there were no irritation reactions in the rabbit cornea, iris, and conjunctiva corresponding to each sample.

[0203] Table 27 Statistical results / points

[0204] Experimental Example 10 Virus elimination experiments were conducted on the gels prepared in Example 9, Example 13, Example 15, Example 20, Example 23, Comparative Example 1 - Comparative Example 3, and Comparative Example 5, commercially available Bentrio, and commercially available iodophor.

[0205] Experimental equipment: Test virus strains: Human coronavirus 229E, human coronavirus NL63, SARS-CoV (causing severe acute respiratory syndrome), novel coronavirus SARS-CoV-2, MERS-CoV (causing Middle East respiratory syndrome), H1N1, HIV-1 virus; Host cells: Vero cells, MT4 cells; Virus-inactivating active ingredient: nasal protective gel; Main instruments and tools: cell culture flasks and 96-well culture plates, constant temperature water bath, carbon dioxide incubator, biosafety cabinet, adjustable pipette, and sterile equipment; Reagents: cell maintenance medium, cell complete medium, fetal bovine serum, deionized water, and standard hard water; Organic interferent: 3% bovine serum albumin solution by mass (prepared by dissolving BSA powder in deionized water); Neutralizer: 10 g / L histidine aqueous solution, 3.0% Tween-80 aqueous solution, and 3 g / L lecithin solution (solvent is PBS); Experimental groups: gels prepared in Example 9, Example 13, Example 15, Example 20, Example 23, Comparative Example 1 - Comparative Example 3, and Comparative Example 5, commercially available Bentrio, and commercially available iodophor; Experimental method: Using human coronavirus 229E with a TCID50 (median tissue culture infective dose) of 10 7 ~10 8 , human coronavirus NL63 with a TCID50 of 10 7 ~10 8 , SARS-CoV (severe acute respiratory syndrome caused by coronavirus) with a TCID50 of 10 7 ~10 8 , SARS-CoV-2 (severe respiratory syndrome coronavirus-2) with a TCID50 of 10 7 ~10 8 , MERS-CoV (Middle East respiratory syndrome coronavirus) with a TCID50 of 10 7 ~10 8 , H1N1 (human influenza A H1N1 virus) with a TCID50 of 10 7 ~10 8 , and HIV-1 virus with a TCID50 of 107 ~10 8 The suspension of HIV-1 virus (human immunodeficiency virus type 1) with a titer of ~10 was diluted 10 times with 3% bovine serum albumin solution and reserved for use; Neutralizer identification test: The residual disinfectant was removed by the neutralization dilution method. The gel of the present invention was used as the stock solution in the test, with an action time of 3 min, an experimental temperature of 20°C ± 1°C, and the test was repeated 3 times; Various virus removal tests: The residual preparation was removed by the neutralization dilution method. The gel of the present invention was used as the stock solution in the test, with action times of 1.5 min, 3 min, and 4.5 min, an experimental temperature of 20°C ± 1°C, and the test was repeated 3 times.

[0206] The experimental results are shown in Table 28. For the gels prepared in Example 9, Example 13, Example 15, Example 20, Example 23 and Comparative Example 1 - Comparative Example 3, Comparative Example 5, commercially available Bentrio, and commercially available iodophor, under the condition of an experimental temperature of 20°C ± 1°C, after 3 repeated tests, for the gels of Example 9, Example 13, Example 15, Example 20, and Example 23 with the stock solution acting for 3 minutes, the average log removal values for human coronavirus 229E, human coronavirus NL63, SARS-CoV, novel coronavirus SARS-CoV-2, MERS-CoV, H1N1, and HIV-1 virus are all far greater than 5, and the effect is far better than the gels prepared in Comparative Example 1 - Comparative Example 3, Comparative Example 5, commercially available iodophor, and commercially available Bentrio, further indicating that the gel of the present invention has a better virus removal effect. The gels prepared by using mussel adhesive protein in Example 15 and Example 23 have a better antiviral effect.

[0207] It shows that the neutralizer used in the neutralization dilution method can effectively neutralize the gel of the present invention, and the neutralizer solution and the neutralization product solution have no effect on the growth of human coronavirus 229E, human coronavirus NL63, SARS-CoV (causing severe acute respiratory syndrome), novel coronavirus SARS-CoV-2, MERS-CoV (causing Middle East respiratory syndrome), H1N1, HIV-1 virus and cells; under the condition of an experimental temperature of 20°C ± 1°C, when the nasal protective gel preparation of the present invention acts for 3 min, the log removal values for human coronavirus 229E, human coronavirus NL63, SARS-CoV (causing severe acute respiratory syndrome), novel coronavirus SARS-CoV-2, MERS-CoV (causing Middle East respiratory syndrome), H1N1, and HIV-1 virus are all greater than 5.00; it is proved that the nasal protective gel preparation of the present invention is effective in removing viruses and is superior to the existing marketed products in terms of effect.

[0208] Table 28 Statistical Results - Virus Removal Experiment - Average Log Removal Value

[0209] Experimental Example 11 Perform a test on the ability of the gels prepared in Example 9, Example 15, Example 20, Example 23, and Comparative Examples 4 - 5 to relieve virus infection.

[0210] Experimental equipment: Virus strains for the test: SARS-CoV-2, the novel coronavirus; Host cells: human respiratory epithelial cells, Vero cells; Antiviral active ingredient: nasal protective gel; Main instruments and tools: cell culture flasks and 96-well culture plates, constant temperature water bath, carbon dioxide incubator, biosafety cabinet, adjustable pipettor, and sterile equipment; Reagents: cell maintenance medium, cell complete medium, fetal bovine serum, deionized water, and standard hard water; Organic interferent: bovine serum albumin solution with a mass fraction of 3% (prepared by dissolving BSA powder in deionized water); Neutralizer solution: 10 g / L histidine aqueous solution, 3.0% Tween-80 aqueous solution, and 3 g / L lecithin solution (the solvent is PBS); Experimental groups: gels prepared in Example 9, Example 15, Example 20, Example 23, and Comparative Examples 4 - 5; Control group: normal saline group; Experimental method: To test the ability of the gel to reduce the infection of existing viruses in nasal epithelium, 24 hours after the cells were infected with SARS-CoV-2, the gels prepared in Example 9, Example 15, Example 20, Example 23, and Comparative Examples 4, 5 and normal saline were respectively mixed with the cells, the cells were treated, and the virus titer was detected.

[0211] The experimental results are shown in Table 29. In the case of infection with SARS-CoV-2, Comparative Examples 4 - 5 and the normal saline group showed higher virus titers, while the samples treated with Example 9, Example 15, Example 20, and Example 23 showed lower virus titers. On the second day of treatment, the virus titer of the comparative examples was 4.8 to 6.91 times that of the examples, and the virus titer of the normal saline group was 5.4 to 7.5 times that of the examples. On the third day of treatment, the virus titer of the examples had started to decline, while the virus titers of Comparative Examples 4 - 5 and the normal saline group remained the same or increased. Therefore, the gel prepared in this application has stronger antiviral ability.

[0212] Table 29 Statistical results / PFU / mL

[0213] Experimental Example 12 Perform film-forming property tests on the gels prepared in Example 23, Example 24, Example 26, Example 27 and Comparative Example 1, and the commercially available Bentrio.

[0214] Take 3 mL of the gel and drop it into a petri dish with a diameter of 80 mm. After putting on disposable rubber gloves, evenly apply the gel with fingers to make the gel disperse evenly. Place the petri dish containing the gel in a constant temperature and humidity chamber at a temperature of 37 °C and a humidity of 65% RH ± 15% RH, and dry for five minutes to observe whether a film is formed.

[0215] The experimental results are shown in Table 30. Since the gel component was not added in Comparative Example 1, no film was formed. The commercially available Bentrio also did not form a film within five minutes, while the gels in Example 23 - Example 24 and Example 26 - Example 27 could form films. Therefore, the gel prepared in this application has a fast film-forming speed, further improving the blocking effect on viruses, microorganisms or bacteria.

[0216] Table 30 Experimental Results

[0217] Experimental Example 13 Test the bacteriostatic performance of the gels prepared in Example 13 - Example 14, Example 31 - Example 32, Comparative Example 2 - Comparative Example 3 and the commercially available Bentrio through a dry-state bacteriostatic test device.

[0218] Challenge inoculum preparation: Take 0.1 mL of Serratia marcescens liquid and drop it onto a nutrient agar medium. Use a sterile L-shaped spreading rod to spread the bacterial liquid evenly on the plate in the same direction so that the bacterial liquid penetrates into the medium, and incubate overnight at 26 °C to obtain the challenge inoculum. Serratia marcescens is selected because it is the smallest among the currently known bacteria, and using this bacterium for the test is representative.

[0219] Experimental group sample preparation: Take a nylon filter membrane (pore size 10 μm, diameter 150 mm) and a petri dish, and perform high-pressure steam sterilization. Sterilization conditions: 121 °C, 30 min. Lay the nylon filter membrane flat in the petri dish, and evenly and dispersedly drop the gel on the nylon filter membrane with a sterile dropper, and spread it evenly. The amount dropped should completely wet the entire nylon filter membrane (2 mL). Place it in a laminar flow hood and dry for 24 h to form a film. Ensure that the pores on the nylon filter membrane are completely covered by the protective film formed by the gel. After obtaining the sample (the nylon filter membrane completely covered by the gel film), note that the nylon filter membrane should not be bent when taken out to prevent damage to the formed film.

[0220] Positive control (nylon filter membrane bacteria penetration verification) group sample preparation: Take a nylon filter membrane (pore size 10 μm, diameter 150 mm), and the other test steps are the same as those for the experimental group sample preparation except that the gel is not dropped.

[0221] Detection method: Clamp the sample between the challenge chamber and the sampling chamber, with the gel drop surface of the sample facing the challenge chamber. Fix it firmly with the fixing screws to ensure no leakage of the challenging microorganisms. Wipe the challenging inoculum with a sterile swab and inoculate it onto the surface of the sample through the opening of the challenge chamber, spreading it as evenly as possible (spreading with a force that does not poke out pits). Seal the openings of the challenge chamber and the sampling chamber of the test device, and place the test device in an incubator at 26°C. After 24 hours, take it out, pre-wet a sterile swab in sterile physiological saline and squeeze out the excess water, then wipe all the inner surfaces of the sample as much as possible through the opening of the sampling chamber, rotating and wiping back and forth 3 times (wiping with a force that does not poke out pits), and then inoculate it in the way of wiping the surface of a nutrient agar plate. Use 3 sterile swabs to wipe each sample and inoculate them on 3 nutrient agar plates respectively. Place the 3 nutrient agar plates in an incubator at 26°C for 24 hours. After the specified time, sample and analyze whether Serratia marcescens grows on the 3 sampling surfaces of the nutrient agar plates; in the same way, wipe all the inner surfaces of the sample as much as possible through the opening of the challenge chamber, rotating and wiping back and forth 3 times (wiping with a force that does not poke out pits), and then inoculate it in the way of wiping the surface of a nutrient agar plate. Use 3 sterile swabs to wipe each sample and inoculate them on 3 nutrient agar plates respectively. Place the 3 nutrient agar plates in an incubator at 26°C for 24 hours. After the specified time, sample and analyze whether Serratia marcescens grows on the 3 challenge chamber sampling surfaces of the nutrient agar plates.

[0222] The results are shown in Table 31. Examples 13 - 14 and Examples 31 - 32 all passed the bacteria barrier test. It was shown that no Serratia marcescens grew in the sampling chamber of the sample, while Serratia marcescens grew in the challenge chamber of the sample. That is, after the bacteria were fixed on the membrane, due to the strong adsorption ability of the biomolecular intercalation composite material, the bacteria could not pass through the membrane. While the commercially available Bentrio, Comparative Example 2, and Comparative Example 3 did not pass the bacteria barrier test, and it was shown that Serratia marcescens grew in both the sampling chamber and the challenge chamber of the sample, because they either did not have adsorption ability or had low adsorption ability. Serratia marcescens grew in the sampling chamber of the positive control, indicating that the nylon filter membrane itself could allow bacteria to pass through. Therefore, the gel prepared in this application has a dual protection function, which can not only form a film to block bacteria but also prevent the bacteria adhered to the surface of the membrane from passing through the membrane.

[0223] Table 31 Experimental Results

[0224] Note: "+" indicates the growth of Serratia marcescens; "-" indicates no growth of Serratia marcescens.

[0225] In summary, (1) the gel prepared by the present invention has no skin irritation, no acute oral toxicity, and no acute eye irritation; (2) the gel prepared by the present invention has an effective and persistent scavenging effect on human coronavirus 229E, human coronavirus NL63, SARS-CoV, novel coronavirus SARS-CoV-2, MERS-CoV, H1N1, and HIV-1 viruses; (3) the gel prepared by the present invention not only has a bactericidal effect on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, but also has a role in blocking bacteria; (4) the gel prepared by the present invention can quickly form a film within 5 minutes, showing instantaneity; (5) the action time of the gel prepared by the present invention is persistent, with the retention percentage at 10 h ranging from 3.2% to 10.3%; (6) the adsorption amount of the biomolecule intercalated composite material prepared by the present invention is relatively excellent, with the adsorption amount at 10 h ranging from 111.3 mg / g to 122.7 mg / g.

Claims

1. A nasal protective gel, characterized in that: Calculated by mass percentage, the composition comprises 0.05%-6% of biomolecule intercalation composite material, 0.04%-30% of in-situ gel material, 0.01%-34% of auxiliary material, and the balance is water.

2. The nasal protective gel according to claim 1, characterized in that The raw materials for preparing the biomolecule intercalation composite material include biomolecules and carrier materials; The biomolecule includes at least one of a polysaccharide and a protein; The support material includes a clay mineral.

3. The nasal protective gel according to claim 2, characterized in that: At least one of the following conditions is met: (1) The clay mineral includes at least one of bentonite, montmorillonite, laponite, kaolinite and hydrotalcite; (2) The polysaccharide comprises at least one of chitosan, chitosan oligosaccharide, quaternized chitosan, quaternized chitosan oligosaccharide, β-glucan, and seaweed polysaccharide; (3) The protein includes at least one of mussel mucin and silk fibroin; (4) The mass ratio of the biomolecule to the carrier material is (50~90):(5~50).

4. The nasal protective gel according to any one of claims 1 to 3, characterized in that: The in-situ gel material includes at least one of a temperature-sensitive gel material, an ion-sensitive gel material, and a pH-sensitive gel material.

5. The nasal protective gel according to claim 4, characterized in that: The temperature-sensitive gel material includes at least one of poloxamer 407, poloxamer 188, poly (N-isopropylacrylamide), polyoxyethylene-polylactic acid-co-glycolic acid, methyl cellulose, and xylan.

6. The nasal protective gel according to claim 5, characterized in that: The temperature-sensitive gel material is poloxamer 407, and the content of poloxamer 407 is 10-30% based on the mass of the nasal protective gel; or The temperature-sensitive gel material is poloxamer 188, and based on the mass of the nasal protective gel, the content of poloxamer 188 is 5-30%; or The temperature-sensitive gel material is poly(N-isopropylacrylamide), and the content of poly(N-isopropylacrylamide) is 20-30% based on the mass of the nasal protective gel; or The temperature-sensitive gel material is polyoxyethylene-polylactic-co-glycolic acid copolymer, and the content of the polyoxyethylene-polylactic-co-glycolic acid copolymer is 15-30% based on the mass of the nasal protective gel; or The temperature-sensitive gel material is methyl cellulose, and the content of methyl cellulose is 1-10% based on the mass of the nasal protective gel; or The temperature-sensitive gel material is xylan, and based on the mass of the nasal protective gel, the content of xylan is 0.1-3%.

7. The nasal protective gel according to claim 4, characterized in that: The ion-sensitive gel material includes at least one of deacetylated gellan gum, sodium alginate, xanthan gum, Brunei gum and carrageenan.

8. The nasal protective gel according to claim 7, characterized in that: The ion-sensitive gel material is deacetylated gellan gum, and the content of the deacetylated gellan gum is 0.04-3% based on the mass of the nasal protective gel; or The ion-sensitive gel material is sodium alginate, and the content of sodium alginate is 0.2-10% based on the mass of the nasal protective gel; or The ion-sensitive gel material is xanthan gum, and the content of xanthan gum is 0.1-8% based on the mass of the nasal protective gel; or The ion-sensitive gel material is Brunei gum, and the content of Brunei gum is 0.1-8% based on the mass of the nasal protective gel; or The ion-sensitive gel material is carrageenan, and based on the mass of the nasal protective gel, the content of carrageenan is 0.04-2%.

9. The nasal protective gel according to claim 4, characterized in that: The pH sensitive gel material includes at least one of cellulose acetate phthalate and carbomer.

10. The nasal protective gel according to claim 9, characterized in that The pH sensitive gel material is cellulose acetate phthalate, and the content of cellulose acetate phthalate is 10-30% based on the mass of the nasal protective gel; or The pH sensitive gel material is carbomer, and based on the mass of the nasal protective gel, the content of carbomer is 0.01-0.5%.

11. The nasal protective gel according to any one of claims 1 to 3, characterized in that: The auxiliary material includes at least one of an osmotic pressure regulator, a gel regulator, a moisturizer, and a pH regulator.

12. The nasal protective gel according to claim 11, characterized in that At least one of the following conditions is met: (1) The osmotic pressure regulator includes at least one of mannitol, sorbitol, sodium citrate, potassium chloride, and sodium chloride; (2) Based on the mass of the nasal protective gel, the content of the osmotic pressure regulator is 0.05-5%; (3) The gel regulator includes at least one of pectin, hydroxymethyl cellulose and hydroxypropyl cellulose; (4) Based on the mass of the nasal protective gel, the content of the gel regulator is 0.05-1%; (5) The moisturizer includes at least one of polyethylene glycol 400, glycerin, propylene glycol, and polysorbate; (6) The pH adjuster includes at least one of sodium hydroxide, triethanolamine, potassium hydroxide, hydrochloric acid, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate and dipotassium hydrogen phosphate; (7) The pH of the nasal protective gel is 3.5-8.

0.

13. The nasal protective gel according to claim 11, characterized in that The moisturizing agent is glycerin, and the content of glycerin is 3-20% based on the mass of the nasal protective gel; or The moisturizing agent is propylene glycol, and the content of propylene glycol is 5-20% based on the mass of the nasal protective gel; or The moisturizing agent is polysorbate, and the content of polysorbate is 0.1-5% based on the mass of the nasal protective gel; or The moisturizing agent is polyethylene glycol 400, and the content of polyethylene glycol 400 is 5-10% based on the mass of the nasal protective gel.

14. A method for preparing the nasal protective gel according to any one of claims 1 to 13, characterized in that: The following steps are involved: The auxiliary material, the in-situ gel material, the biomolecule intercalation composite material and water are mixed to obtain the product.

15. The method for preparing the nasal protective gel according to claim 14, characterized in that: The preparation method of the biomolecule intercalation composite material comprises: mixing the carrier material, biomolecules and solvent, reacting, solid-liquid separation, and drying to obtain the composite material.

16. A preparation, characterized in that The nasal protective gel comprises the nasal protective gel according to any one of claims 1 to 13 or the nasal protective gel prepared according to the preparation method of the nasal protective gel according to claim 14 or 15.

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