Long-acting microbial inhibition paste based on microsphere slow release technology and preparation method thereof

Abstract

The invention provides a long-acting microbial inhibition paste based on a microsphere slow release technology and a preparation method thereof. The long-acting microbial inhibition paste based on the microsphere slow release technology comprises a chlorine dioxide slow release agent, an acidifying agent, a moisture guiding agent, a dispersing agent, a catalyst, an aromatic, a preservative, a plasticizer, sodium carboxymethyl cellulose, polyvinyl alcohol and an adhesive. The chlorine dioxide sustained-release agent is chlorine dioxide sustained-release microspheres; the effective component of the chlorine dioxide sustained-release microspheres comprises sodium chlorite. The long-acting microbial inhibition paste based on the microsphere slow-release technology provided by the invention can be used for continuously generating chlorine dioxide to achieve a slow-release effect; the microbial inhibition paste is convenient to carry, can be used as an antibacterial coating material for a long time, and is smeared on the surface of an object to achieve antibacterial and disinfection effects; wound infection, such as wound nursing after an operation, can be prevented; the traditional Chinese medicine composition can also be used for treating skin inflammation, acne and other problems, and has a wide application prospect.

Description

Technical Field

[0001] This invention relates to the field of bactericidal ointment technology, specifically to a long-acting microbial inhibitory ointment based on microsphere sustained-release technology and its preparation method. Background Technology

[0002] Chlorine dioxide is a safe, highly efficient, broad-spectrum, and potent non-toxic bactericide. Because it does not undergo a chlorine substitution reaction, it does not produce any teratogenic, carcinogenic, or other harmful substances. Its effective chlorine content is 2.63 times that of chlorine gas, its bactericidal ability is 5 times that of chlorine gas, and it is more than 50 times that of sodium hypochlorite. Therefore, it can exert a strong antibacterial effect even at low concentrations. Chlorine dioxide has no toxic side effects on the human body when used at low concentrations. Unlike some traditional antibacterial drugs, it does not cause drug resistance problems or damage the human immune system. After use, chlorine dioxide gradually decomposes into harmless substances and does not pollute the environment. Currently, existing surface disinfection methods are incomplete and short-lasting. There is no long-acting microbial inhibitory paste using chlorine dioxide in this field, and there is an urgent need to provide a new type of long-acting microbial inhibitory paste to overcome the shortcomings of existing surface disinfection methods. Summary of the Invention

[0003] To address the aforementioned technical problems, this invention provides a long-acting microbial inhibitory paste based on microsphere sustained-release technology and its preparation method. In this invention, the long-acting microbial inhibitory paste based on microsphere sustained-release technology inherently possesses antibacterial properties or has undergone antibacterial treatment to achieve antibacterial and bacteriostatic effects. It kills or inhibits the growth of microorganisms on the surface through chemical reactions or physical actions, thereby exerting an antibacterial effect. This invention can spontaneously undergo a chemical reaction in the air to produce chlorine dioxide for sterilization and disinfection. It has a large contact area with air, and the film material has a certain air-isolation effect. The chemical reaction proceeds slowly but continuously, allowing for the continuous production of chlorine dioxide and achieving a sustained-release effect.

[0004] According to this invention, unlike some short-acting antibacterial agents, chlorine dioxide microbial inhibitory ointment can continuously release chlorine dioxide molecules, thereby achieving a long-lasting antibacterial effect. After application, the ointment forms a protective film on the skin surface, continuously inhibiting microbial growth and prolonging the duration of its antibacterial effect. This is particularly important for the treatment of chronic wounds and the prevention of infection recurrence. Chlorine dioxide has no toxic side effects on the human body when used at low concentrations. It does not cause drug resistance problems like some traditional antibacterial drugs, nor does it damage the human immune system. This allows chlorine dioxide microbial inhibitory ointment to be used long-term without concern for adverse effects on the body. After use, chlorine dioxide gradually decomposes into harmless substances, without polluting the environment. Compared with some antibacterial agents containing heavy metals or other harmful substances, chlorine dioxide microbial inhibitory ointment is more environmentally friendly and safer, meeting the modern society's demand for green and environmentally friendly products.

[0005] In a first aspect, the present invention provides a long-acting microbial inhibitory paste based on microsphere sustained-release technology, comprising a chlorine dioxide sustained-release agent, an acidifier, a humectant, a dispersant, a catalyst, a fragrance, a preservative, a plasticizer, polyvinyl alcohol, and a binder; wherein the chlorine dioxide sustained-release agent is chlorine dioxide sustained-release microspheres; and the effective component of the chlorine dioxide sustained-release microspheres includes sodium chlorite.

[0006] Preferably, by weight, the product comprises: 16-24 parts of chlorine dioxide sustained-release microspheres, 45-86.5 parts of acidifier, 32-48 parts of humectant, 80-120 parts of dispersant, 0.2-0.36 parts of catalyst, 3-6 parts of fragrance, 0.3-1.2 parts of preservative, 10-24 parts of plasticizer, 8-15.5 parts of sodium carboxymethyl cellulose, 22-77.5 parts of polyvinyl alcohol, and 12-19.5 parts of binder. By optimizing the types and amounts of each component, this invention can fully leverage the synergistic effect between components, significantly improving the efficacy of the long-acting microbial inhibitory paste based on microsphere sustained-release technology. More preferably, the composition includes 16-24 parts of chlorine dioxide slow-release microspheres, 57-86.5 parts of acidifier, 32-48 parts of humectant, 80-120 parts of dispersant, 0.24-0.36 parts of catalyst, 4-6 parts of fragrance, 0.8-1.2 parts of preservative, 16-24 parts of plasticizer, 10.2-15.5 parts of sodium carboxymethyl cellulose, 51.5-77.5 parts of polyvinyl alcohol, and 12.8-19.5 parts of binder.

[0007] This invention utilizes a specific ratio of chlorine dioxide slow-release agent, acidifier, humectant, dispersant, catalyst, fragrance, preservative, plasticizer, polyvinyl alcohol, and binder to create a long-lasting microbial inhibitory ointment based on microsphere slow-release technology. Sodium chlorite in the chlorine dioxide slow-release agent serves as a precursor for chlorine dioxide and is mixed with activators, film-forming agents, and other raw materials. Finally, the mixture is applied to form a film, which spontaneously undergoes a chemical reaction in the air to produce chlorine dioxide for sterilization and disinfection. Thanks to the large surface area of ​​the film and its excellent air-sealing properties, the chemical reaction proceeds slowly but continuously, resulting in sustained chlorine dioxide production and a slow-release effect. The microbial inhibitory ointment is typically packaged in small tubes or bottles for easy portability. It can be used not only as an antibacterial coating material for long-term application, exerting antibacterial and disinfecting effects when applied to surfaces; it can also be used to prevent wound infections, such as in postoperative wound care; and it can be used to treat skin inflammation, acne, and other problems, demonstrating broad application prospects.

[0008] Preferably, the sodium chlorite content in the chlorine dioxide sustained-release microspheres is 10% to 60% by mass; for example, 20%, 30%, 40%, 50%, 55%, 60%, etc., preferably 30% to 52%. Using chlorine dioxide sustained-release microspheres containing a certain amount of sodium chlorite can better exert its effect in the long-acting microbial inhibitory ointment based on microsphere sustained-release technology of the present invention, further improving its overall performance.

[0009] Preferably, the chlorine dioxide slow-release microspheres are prepared by mixing a sodium chlorite-containing microsphere precursor with a calcium chloride solution, wherein the sodium chlorite-containing microsphere precursor is prepared by membrane emulsification.

[0010] Preferably, the acidifying agent is selected from one or more of sodium bisulfate, citric acid, malic acid, tartaric acid, fumaric acid, and sorbic acid; more preferably, the acidifying agent is citric acid. In this invention, by selecting a preferred acidifying agent, the pH value of the ointment can be effectively adjusted, promoting the release and activity of the components, improving the long-lasting antibacterial effect of the microbial inhibitory ointment, enhancing its antibacterial ability during use, and ensuring that the antibacterial effect of the product does not weaken after long-term use.

[0011] Preferably, the humectant is selected from one or more of calcium chloride, magnesium chloride, lithium chloride, silica gel, aluminum glue, zeolite, quicklime, charcoal, diatomaceous earth, and perlite; more preferably, the humectant is calcium chloride or magnesium chloride. By using humectants selected from the above, moisture can be effectively absorbed, maintaining the wettability of the ointment, increasing product stability, and extending its shelf life. This further enhances the long-lasting antibacterial effect and user experience of the microbial inhibitory ointment.

[0012] Preferably, the dispersant is selected from one or more of petrolatum, gelatin, pectin, gum arabic, and carrageenan; more preferably, the dispersant is gum arabic or pectin.

[0013] Preferably, the catalyst is selected from one or more of the following: solid acid catalysts, organic base catalysts, metal catalysts, metal oxide catalysts, complex catalysts, rare earth catalysts, molecular sieve catalysts, biocatalysts, and nanocatalysts. Examples include triethylamine, zinc oxide, ethylenediaminetetraacetic acid (EDTA) metal complexes, and cerium oxide.

[0014] Preferably, the fragrance is selected from one or more of benzene hydrocarbons, monobenzene aromatic hydrocarbons (such as benzene, phenol, halogenated benzene, toluene, etc.), polycyclic aromatic hydrocarbons, and polycyclic hydrocarbons having a benzene ring or a shared ring edge of heterocyclic compounds. Examples include benzyl alcohol, phenylethanol, and benzopyranone. Preferably, the preservative is selected from one or more of benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, and calcium propionate.

[0015] Preferably, the plasticizer is selected from one or more of triethyl citrate, tributyl citrate, isosorbide dioctanoate, PEG4000, sodium carboxymethyl cellulose, PEG8000, acetylated ricinoleic acid, dimethyl glycerol, and epoxidized soybean oil. More preferably, the plasticizer is PEG4000 or PEG8000.

[0016] Preferably, the adhesive is made of low-density polyethylene.

[0017] In this invention, the aforementioned raw materials work synergistically to solve and optimize the long-lasting antibacterial and disinfecting properties of the long-acting microbial inhibitory paste based on microsphere sustained-release technology. By optimizing the types and amounts of raw materials, the overall performance of the long-acting microbial inhibitory paste based on microsphere sustained-release technology can be further improved.

[0018] Further optimization yields the following components: 18-22 parts chlorine dioxide slow-release microspheres, 64.8-79.2 parts acidifier, 36-44 parts humectant, 90-110 parts dispersant, 0.27-0.33 parts catalyst, 4.5-5.5 parts fragrance, 0.9-1.1 parts preservative, 18-22 parts plasticizer, 11.52-14.08 parts sodium carboxymethyl cellulose, 57.96-70.84 parts polyvinyl alcohol, and 14.4-17.6 parts binder. Using the preferred weight ratios yields better results.

[0019] More preferably, the composition includes 19-21 parts of chlorine dioxide slow-release microspheres, 68.4-75.6 parts of citric acid, 38-42 parts of calcium chloride, 95-105 parts of gum arabic, 0.285-0.315 parts of zinc oxide, 4.75-5.25 parts of benzyl alcohol, 0.95-1.05 parts of benzoic acid, 19-21 parts of PEG4000, 12.16-13.44 parts of sodium carboxymethyl cellulose, 61.18-67.62 parts of polyvinyl alcohol, and 15.2-16.8 parts of low-density polyethylene.

[0020] Secondly, the method for preparing a long-acting microbial inhibitory ointment based on microsphere sustained-release technology provided by the present invention includes: 1) Polyvinyl alcohol gel is prepared using polyvinyl alcohol, water, plasticizer and sodium carboxymethyl cellulose; the polyvinyl alcohol gel, acidifier, catalyst, fragrance and preservative are mixed and dried to form a film to obtain paste A.

[0021] 2) Mix the dispersant, dichloromethane, chlorine dioxide slow-release microspheres and humectant, and dry to form a film to obtain paste B.

[0022] 3) Dry-combine the A paste and the B paste.

[0023] Preferably, the preparation of the chlorine dioxide sustained-release microspheres in the chlorine dioxide sustained-release agent includes: using an aqueous solution containing sodium chlorite and sodium alginate as the internal phase, and a mineral oil solution containing calcium disodium ethylenediaminetetraacetate or calcium chloride and Span 80 as the external phase, obtaining a microsphere precursor through membrane emulsification; then soaking the microsphere precursor in a calcium chloride solution, filtering, and drying to obtain chlorine dioxide sustained-release microspheres. The chlorine dioxide sustained-release microspheres prepared using the above preferred method can better exert the effect of sodium chlorite and further enhance the long-lasting antibacterial effect.

[0024] The long-acting microbial inhibitory ointment prepared by this invention, based on microsphere sustained-release technology, utilizes the large surface area of ​​the film-forming agent and a film-forming material with a certain, but not absolute, air-isolation effect to control the generation rate of chlorine dioxide, resulting in a significant sustained-release effect. This ointment can also be used as an antibacterial coating, applied to the surface of objects to exert antibacterial and disinfecting effects. The ointment is suitable for various types of wounds, including abrasions, cuts, burns, and scalds. It can also be used to prevent wound infection, such as in postoperative wound care. Furthermore, it can be used to treat skin inflammation, acne, and other problems, showing broad application prospects.

[0025] Preferably, in step 1), the polyvinyl alcohol gel and acidifier are mixed and stirred until there is no insoluble precipitate in the solution, and then the catalyst, fragrance and preservative are added; preferably, in step 1), the mass concentration of polyvinyl alcohol in the polyvinyl alcohol gel is 1% to 10%, the mass ratio of the plasticizer to polyvinyl alcohol is 5 to 20:100, and the mass ratio of carboxymethyl cellulose to polyvinyl alcohol is 0.1 to 0.5:1.

[0026] Preferably, in step 2), the ratio of the dispersant to dichloromethane is 10-15 g: 100 mL.

[0027] Preferably, in step 3), the amount of adhesive used is 10% to 50% of the mass of paste B.

[0028] Preferably, the preparation steps of the chlorine dioxide slow-release microspheres are as follows: 1) Disperse sodium chlorite in deionized water and stir to obtain a mixed solution.

[0029] 2) Add the mixed solution to the sodium alginate solution and stir to mix well to obtain a mixed solution of sodium alginate and sodium chlorite.

[0030] 3) Dissolve Span 80 in mineral oil, then dissolve calcium disodium ethylenediaminetetraacetate or calcium chloride. Crosslink the mixture via membrane emulsification. Immerse the resulting microsphere precursor in a calcium chloride solution, filter, centrifuge, collect, and freeze-dry to obtain chlorine dioxide sustained-release microspheres. The chlorine dioxide sustained-release microspheres prepared using the method of this invention exhibit better performance.

[0031] Further preferred, the preparation steps of the chlorine dioxide sustained-release microspheres are as follows: 1) Disperse 0.5~1.50 g of sodium chlorite into 50 mL of deionized water and stir to obtain a mixed solution.

[0032] 2) Add 50 mL of the mixed solution to 50 mL of a 3-5% sodium alginate solution, stir and mix well to obtain a mixed solution of sodium alginate and sodium chlorite.

[0033] 3) Dissolve 10% by mass of Span 80 in mineral oil, then dissolve 3-6% w / v of calcium disodium ethylenediaminetetraacetate (Ca). - Using EDTA or calcium chloride as the internal phase, a microsphere precursor is obtained by cross-linking via membrane emulsification. The microsphere precursor is then immersed in a 3-6% calcium chloride solution for 30-120 min, filtered, collected by centrifugation, and freeze-dried for 8-16 h to obtain chlorine dioxide slow-release microspheres.

[0034] The long-acting microbial inhibitory ointment based on microsphere sustained-release technology described in this invention can effectively generate chlorine dioxide. Hypochlorite ions in sodium chlorite undergo a redox reaction under acidic conditions to generate chlorine dioxide. The reaction equation is: 5ClO2 - +4H + →4ClO2+Cl - +2H₂O. This reaction requires an acidic environment in which chlorine dioxide is produced. The hygroscopic agent in this invention continuously absorbs moisture from the air, creating a micro-aquatic environment around it. In this aquatic environment, sodium chlorite and the acidifier react to release chlorine dioxide. The surface of the antibacterial film first releases chlorine dioxide upon contact with the air, and then the air gradually penetrates into the inner layer of the long-acting microbial inhibitory paste based on microsphere slow-release technology, further triggering the production of chlorine dioxide. This invention, by utilizing the large surface area of ​​the film agent and the film-forming material with a certain but not absolute air-barrier effect, controls the rate of chlorine dioxide production, resulting in a significant slow-release effect. Simultaneously, the film agent described in this invention can also be used as an antibacterial coating, applied to the surface of items to exert antibacterial and disinfecting effects.

[0035] According to some embodiments of the present invention, a method for preparing a long-acting microbial inhibitory paste based on microsphere sustained-release technology includes the following steps: Step 1: Prepare polyvinyl alcohol gel. Add a plasticizer to the polyvinyl alcohol gel and add sodium carboxymethyl cellulose to increase the stability of the film after drying. The amount of plasticizer added is 5% to 20% of the mass of polyvinyl alcohol in the hydrogel, and the mass ratio of the added carboxymethyl cellulose to polyvinyl alcohol is 0.1 to 0.5.

[0036] Step 2: Select hydrogel polyvinyl alcohol as the film-forming substrate. Add acidifier, catalyst, fragrance, and preservative to the hydrogel in sequence, and then dry it through a casting process to form paste A. In the preparation process of film A, the mass concentration of polyvinyl alcohol in the prepared polyvinyl alcohol gel is 1%~10%. When mixing polyvinyl alcohol gel and acidifier, mix polyvinyl alcohol gel and acidifier according to the mass ratio first, and stir continuously with an electric mixer until there is no insoluble precipitate in the solution, and then add catalyst, fragrance, and preservative.

[0037] Step 3: Dissolve the dispersant in dichloromethane, add chlorine dioxide slow-release microspheres, mix well, add a humectant, mix again, volatilize the dichloromethane at 50°C, and apply as paste B using a flatbed coater; wherein, when mixing dichloromethane and dispersant, the mass ratio of dispersant to volume of dichloromethane is 10~15g:100mL.

[0038] Step 4: When laminating paste A and paste B, use low-density polyethylene or an adhesive. The amount of adhesive used is 10% to 50% of the mass of film B.

[0039] The long-acting microbial inhibitory ointment based on microsphere sustained-release technology provided by this invention not only promotes wound healing and reduces inflammatory responses, but also inhibits the release of inflammatory mediators, reducing symptoms such as redness, swelling, and pain, creating a favorable environment for wound repair. It is also very convenient to use; the chlorine dioxide microbial inhibitory ointment typically has good texture and spreadability, making it easy to apply to the wound surface. It can evenly cover the wound, forming a protective film that effectively exerts its antibacterial and healing-promoting effects. The microbial inhibitory ointment is usually packaged in small tubes or bottles for easy portability. It can be used anytime, anywhere—at home, in the office, or while traveling—to conveniently address various sudden wound infections. The chlorine dioxide microbial inhibitory ointment is suitable for various types of wounds, including abrasions, cuts, burns, and scalds. It can also be used to prevent wound infection, such as in postoperative wound care. Furthermore, it can be used to treat skin inflammation, acne, and other problems, showing broad application prospects. Attached Figure Description

[0040] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0041] Figure 1 Images of responsive chlorine dioxide slow-release microspheres according to an embodiment of the present invention.

[0042] Figure 2 Images of the microbial inhibitory pastes from the embodiments and comparative examples of the present invention after overnight incubation. Detailed Implementation

[0043] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0044] The endpoints and any values ​​of the ranges disclosed in this invention are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this invention.

[0045] Unless otherwise specified, the techniques or conditions described in the embodiments of this invention shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Devices, instruments, reagents, etc., without specified manufacturers, are all conventional products that can be purchased through legitimate channels. All experimental reagents and raw materials involved are commercially available products, and all reagents are analytical grade products.

[0046] Example 1 This embodiment provides a long-acting microbial inhibitory paste based on microsphere sustained-release technology, with the following raw materials in the following weight ratio: sodium chlorite 2g, acidifier (citric acid) 4.6g, humectant (calcium chloride) 3.2g, dispersant (gum arabic) 8.92g, catalyst (zinc oxide) 0.02g, fragrance (benzyl alcohol) 0.3g, preservative (benzoic acid) 0.03g, plasticizer (PEG4000) 1g, sodium carboxymethyl cellulose 0.8g, polyvinyl alcohol 2.2g, and binder (low-density polyethylene) 1.412g.

[0047] This embodiment provides a method for preparing the above-mentioned long-acting microbial inhibitory paste based on microsphere sustained-release technology, including the following steps: Step 1: Weigh 2.2g of polyvinyl alcohol and dissolve it in 100mL of aqueous solution. Heat at 90℃ and stir constantly until the polyvinyl alcohol is dissolved.

[0048] Step 2: After the polyvinyl alcohol aqueous solution cools to room temperature, slowly add 1g of PEG4000 and 0.8g of sodium carboxymethyl cellulose to the solution in sequence, stirring while pouring with an electric mixer to prepare a polyvinyl alcohol gel of a certain concentration. After stirring evenly, slowly add 4.6g of citric acid powder to the gel.

[0049] Step 3: Use an electric mixer to continuously stir until there is no sediment. Then add 0.02g of catalyst, 0.3g of fragrance and 0.03g of preservative to the gel in sequence. Cast the gel into a film using an AFA-II automatic coating machine and dry it at 40℃ and RH24% for 12 hours to make paste A.

[0050] Step 4: Weigh 8.92g of gum arabic and dissolve it in 100mL of dichloromethane. Add 2g of sodium chlorite and mix well with an electric mixer. Then add 3.2g of calcium chloride and mix. Place the solution in a 50℃ drying oven to dry the dichloromethane. After cooling to room temperature, apply it as paste B using a flatbed coater.

[0051] Step 5: Apply a layer of low-density polyethylene adhesive to the dried A paste using an AFA-II automatic coating machine. At this time, the amount of low-density polyethylene used is 10% of the mass of B paste. Then, use a coating machine to laminate B paste to form a slow-release chlorine dioxide antibacterial film with a thickness of 0.29 mm.

[0052] Place 4g of antibacterial film in an open plastic bottle with a diameter of 3.67cm, a height of 4cm, and a volume of 110mL. In an environment of 24℃ and RH24%, close the bottle cap for 2 hours every 22 hours and then use a chlorine dioxide gas detector to measure the concentration of chlorine dioxide gas in the bottle. If the concentration can be measured, it indicates that the tablet is still releasing chlorine dioxide.

[0053] Example 2 This embodiment provides a long-acting microbial inhibitory paste based on microsphere sustained-release technology, comprising the following raw materials in the following weight ratio: 2g chlorine dioxide sustained-release microspheres, 7.2g acidifier (citric acid), 4g humectant (calcium chloride), 10g dispersant (gum arabic), 0.03g catalyst (zinc oxide), 0.5g fragrance (benzyl alcohol), 0.1g preservative (benzoic acid), 2g plasticizer (PEG4000), 1.28g sodium carboxymethyl cellulose, 6.44g polyvinyl alcohol, and 1.6g binder (low-density polyethylene). The chlorine dioxide sustained-release microspheres are prepared by mixing a sodium chlorite-containing microsphere precursor prepared via membrane emulsification with a calcium chloride solution. The sodium chlorite content in the chlorine dioxide sustained-release microspheres is 50% by mass.

[0054] The preparation steps of the chlorine dioxide sustained-release microspheres are as follows: 1) Disperse 1.5 g of sodium chlorite into 50 mL of deionized water and stir to obtain a mixed solution.

[0055] 2) Add 50 mL of the mixed solution to 50 mL of a 5% sodium alginate solution, stir and mix well to obtain a mixed solution of sodium alginate and sodium chlorite.

[0056] 3) Dissolve 10% Span 80 by mass in 100 mL of mineral oil, then dissolve 3% w / v calcium chloride as the internal phase, and crosslink the mixture via membrane emulsification to obtain a microsphere precursor; immerse the microsphere precursor in a 5% calcium chloride solution for 30 min, filter, collect by centrifugation, and freeze-dry for 8 h to obtain chlorine dioxide sustained-release microspheres. Figure 1 ), with a size of 11um ± 1.2um.

[0057] This embodiment provides a method for preparing the above-mentioned long-acting microbial inhibitory paste based on microsphere sustained-release technology, including the following steps: Step 1: Weigh 6.44g of polyvinyl alcohol and dissolve it in 100mL of aqueous solution. Heat at 90℃ and stir constantly until the polyvinyl alcohol is dissolved.

[0058] Step 2: After the polyvinyl alcohol aqueous solution cools to room temperature, slowly add 2g of PEG4000 and 1.28g of sodium carboxymethyl cellulose to the solution in sequence, stirring while pouring with an electric mixer to prepare a polyvinyl alcohol gel of a certain concentration. After stirring evenly, slowly add 7.2g of citric acid powder to the gel.

[0059] Step 3: Use an electric mixer to continuously stir until there is no sediment. Then add 0.03g of catalyst, 0.5g of fragrance and 0.1g of preservative to the gel in sequence. Cast the gel into a film using an AFA-II automatic coating machine and dry it at 40℃ and RH24% for 12 hours to make paste A.

[0060] Step 4: Weigh 10g of gum arabic and dissolve it in 100mL of dichloromethane. Then add 2g of chlorine dioxide slow-release microspheres and mix them evenly with an electric stirrer. Then add 4g of calcium chloride and mix. Place the solution in a 50℃ forced-air drying oven to dry the dichloromethane. After cooling to room temperature, apply it as paste B using a flat plate coater.

[0061] Step 5: Apply a layer of low-density polyethylene adhesive to the dried A paste using an AFA-II automatic coating machine. At this time, the amount of low-density polyethylene used is 10% of the mass of the B film. Then, use the coating machine to laminate the B paste to make a slow-release chlorine dioxide antibacterial film with a thickness of 0.34 mm.

[0062] Example 3 This embodiment provides a long-acting microbial inhibitory ointment based on microsphere sustained-release technology, using the same method as in Example 2, except that the calcium chloride in the internal phase of the chlorine dioxide sustained-release microsphere preparation process is replaced with calcium disodium ethylenediaminetetraacetate.

[0063] Comparative Example 1 This comparative example provides a microbial inhibitory paste, which uses the same method as in Example 2, except that it does not use a sustained-release agent or sustained-release microspheres.

[0064] Step 1: Slowly add 4.6g of citric acid powder to 10ml of aqueous solution.

[0065] Step 2: After no more precipitate is formed, add 0.02g of catalyst, 0.3g of fragrance and 0.03g of preservative to the solution in sequence. Cast the mixture into a film using an AFA-II automatic coating machine and dry it at 40℃ and RH24% for 12 hours to make paste A.

[0066] Step 3: Weigh 8.92g of gum arabic and dissolve it in 100mL of dichloromethane. Add 2g of sodium chlorite and mix well with an electric mixer. Then add 3.2g of calcium chloride and mix. Place the solution in a 50℃ forced-air drying oven to dry the dichloromethane. After cooling to room temperature, apply it as paste B using a flatbed coater.

[0067] Step 5: Apply a layer of low-density polyethylene adhesive to the dried A paste using an AFA-II automatic coating machine. At this time, the amount of low-density polyethylene used is 10% of the mass of B paste. Then, use a coating machine to laminate B paste to form a slow-release chlorine dioxide antibacterial film with a thickness of 0.29 mm.

[0068] Place 4g of antibacterial film in an open plastic bottle with a diameter of 3.67cm, a height of 4cm, and a volume of 110mL. In an environment of 24℃ and RH24%, close the bottle cap for 2 hours every 22 hours and then use a chlorine dioxide gas detector to measure the concentration of chlorine dioxide gas in the bottle. If the concentration can be measured, it indicates that the tablet is still releasing chlorine dioxide.

[0069] Experimental Example 1 Following the experimental method of Example 1, the antibacterial films (4g) of the above examples and comparative examples were placed in an open plastic bottle with a diameter of 3.67cm, a height of 4cm, and a volume of 110mL. At 24℃ and RH 24%, the bottle cap was closed for 2 hours every 22 hours, and the concentration of chlorine dioxide gas in the bottle was measured using a chlorine dioxide gas detector. If a concentration could be detected, it indicated that the tablets were still releasing chlorine dioxide slowly. The changes in chlorine dioxide concentration (ppm) of each example and comparative example over the number of days are shown in Table 1.

[0070] Table 1

[0071] Experiment Example 2 The long-acting antimicrobial ointments based on microsphere sustained-release technology from Examples 1-2 and Comparative Example 1 were tested as follows: 1. Spread 100g of sustained-release paste on a petri dish and place it in a 1 cubic meter test chamber at room temperature.

[0072] 2. On days 1, 7, and 15, 100 μL of E. coli (10⁶ CFU) was spread onto the adjacent glass slides.

[0073] 3. After 10 minutes, the sample was placed in a neutralizing agent (1L PBS with 1g sodium thiosulfate + 10g Tween 80 + 5g lecithin).

[0074] 4. Then centrifuge at 6000 rpm for 5 min, resuspend in 100 μL LB medium, spread on solid culture medium, and incubate overnight. Take photos, count, and analyze the results. (See attached image). Figure 2 The sustained-release ointment provided in Example 2 of this invention has the best long-lasting antibacterial effect.

[0075] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A long-acting antimicrobial ointment based on microsphere sustained-release technology, characterized in that, It includes a chlorine dioxide slow-release agent, an acidifier, a humectant, a dispersant, a catalyst, a fragrance, a preservative, a plasticizer, sodium carboxymethyl cellulose, polyvinyl alcohol, and an adhesive; the chlorine dioxide slow-release agent is chlorine dioxide slow-release microspheres; the effective component of the chlorine dioxide slow-release microspheres includes sodium chlorite.

2. The long-acting microbial inhibitory ointment based on microsphere sustained-release technology according to claim 1, characterized in that, By weight, it includes: 16-24 parts of chlorine dioxide slow-release microspheres, 45-86.5 parts of acidifier, 32-48 parts of humectant, 80-120 parts of dispersant, 0.2-0.36 parts of catalyst, 3-6 parts of fragrance, 0.3-1.2 parts of preservative, 10-24 parts of plasticizer, 8-15.5 parts of sodium carboxymethyl cellulose, 22-77.5 parts of polyvinyl alcohol, and 12-19.5 parts of binder.

3. The long-acting microbial inhibitory ointment based on microsphere sustained-release technology according to claim 2, characterized in that, The sodium chlorite content in the chlorine dioxide slow-release microspheres is 10%~60% by mass. And / or, the chlorine dioxide slow-release microspheres are prepared by mixing a sodium chlorite-containing microsphere precursor with a calcium chloride solution, wherein the sodium chlorite-containing microsphere precursor is prepared by membrane emulsification. And / or, the acidifying agent is selected from one or more of sodium bisulfate, citric acid, malic acid, tartaric acid, fumaric acid and sorbic acid; And / or, the humectant is selected from one or more of calcium chloride, magnesium chloride, lithium chloride, silica gel, aluminum glue, zeolite, quicklime, charcoal, diatomaceous earth, and perlite.

4. The long-acting microbial inhibitory ointment based on microsphere sustained-release technology according to any one of claims 1-3, characterized in that, The dispersant is selected from one or more of petrolatum, gelatin, pectin, gum arabic, and carrageenan.

5. The long-acting microbial inhibitory ointment based on microsphere sustained-release technology according to any one of claims 1-3, characterized in that, The catalyst is selected from one or more of the following: solid acid catalysts, organic base catalysts, metal catalysts, metal oxide catalysts, complex catalysts, rare earth catalysts, molecular sieve catalysts, biocatalysts, and nanocatalysts.

6. The long-acting microbial inhibitory ointment based on microsphere sustained-release technology according to any one of claims 1-3, characterized in that, The fragrance is selected from one or more of benzene hydrocarbons, monobenzene aromatic hydrocarbons, polycyclic aromatic hydrocarbons, and polycyclic hydrocarbons having a benzene ring or a heterocyclic ring shared by the ring.

7. The long-acting microbial inhibitory ointment based on microsphere sustained-release technology according to any one of claims 1-3, characterized in that, The preservative is selected from one or more of benzoic acid, sodium benzoate, sorbic acid, potassium sorbate, and calcium propionate.

8. The long-acting microbial inhibitory ointment based on microsphere sustained-release technology according to any one of claims 1-3, characterized in that, The plasticizer is selected from one or more of the following: triethyl citrate, tributyl citrate, isosorbide dioctanoate, PEG4000, PEG8000, acetylated ricinoleic acid, dimethyl glycerol, and epoxidized soybean oil. And / or, the adhesive is low-density polyethylene.

9. A method for preparing the long-acting microbial inhibitory ointment based on microsphere sustained-release technology according to any one of claims 1-8, characterized in that, include: 1) Polyvinyl alcohol gel was prepared using polyvinyl alcohol, water, plasticizer, and sodium carboxymethyl cellulose; The polyvinyl alcohol gel, acidifier, catalyst, fragrance and preservative are mixed and dried to form a film to obtain paste A; 2) Mix the dispersant, dichloromethane, chlorine dioxide slow-release agent, and humectant, and dry to form a film to obtain paste B; 3) Dry-combine the A paste and the B paste; The preparation of the chlorine dioxide sustained-release microspheres in the chlorine dioxide sustained-release agent includes: using an aqueous solution containing sodium chlorite and sodium alginate as the inner phase, and a mineral oil solution containing calcium disodium ethylenediaminetetraacetate or calcium chloride and Span 80 as the outer phase, obtaining a microsphere precursor through membrane emulsification; then soaking the microsphere precursor in a calcium chloride solution, filtering and drying to obtain chlorine dioxide sustained-release microspheres.

10. The method for preparing the long-acting microbial inhibitory ointment based on microsphere sustained-release technology according to claim 9, characterized in that, In step 1), the polyvinyl alcohol gel and acidifier are mixed and stirred until there is no insoluble precipitate in the solution, and then the catalyst, fragrance and preservative are added; and / or, in step 1), the mass concentration of polyvinyl alcohol in the polyvinyl alcohol gel is 1% to 10%, the mass ratio of the plasticizer to polyvinyl alcohol is 5 to 20:100, and the mass ratio of carboxymethyl cellulose to polyvinyl alcohol is 0.1 to 0.5:1; And / or, in step 2), the ratio of the dispersant to dichloromethane is 10~15g:100mL; And / or, in step 3), the amount of adhesive used is 10% to 50% of the mass of paste B.

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