A dual release nanofiber membrane, preparation and use thereof

Abstract

The application discloses a double sustained-release nanofiber membrane, and preparation and application thereof. The preparation of the double sustained-release nanofiber membrane comprises the following steps: S1, dissolving an efficacy molecule in a solution containing a hydrophobic polymer compound to obtain a core layer spinning precursor solution; S2, dissolving a metal nitrate in a solution containing a hydrophilic polymer compound to obtain a shell layer spinning precursor solution; S3, performing coaxial electrospinning on the core layer spinning precursor solution in step S1 and the shell layer spinning precursor solution in step S2, and preparing a nanofiber membrane with a coaxial nanostructure of a metal nitrate by means of an interface effect; and S4, immersing the nanofiber membrane prepared in step S3 in a phosphate solution to perform an anion exchange reaction, so as to obtain a double sustained-release nanofiber membrane with a coaxial nanostructure of a metal phosphate. The prepared double sustained-release nanofiber membrane can realize sustained release of the core layer efficacy molecule and the shell layer metal ion, and thus the skin condition can be further improved.

Description

Technical Field

[0001] This invention relates to the field of cosmetic nanomaterials technology. More specifically, it relates to a dual-release nanofiber membrane, its preparation, and its application. Background Technology

[0002] Facial masks are a common skincare product. Applying a mask containing active ingredients to the face promotes the absorption of these ingredients by the skin, enabling the skin to achieve desired effects such as whitening, moisturizing, and repair.

[0003] Traditional facial masks often have low concentrations of active ingredients and nutrients, with far less readily absorbed active ingredients. Furthermore, the active ingredients in these masks cannot be released continuously, failing to produce effective skincare results. Nanofibers, due to their high specific surface area, high porosity, and high encapsulation efficiency, and their suitability as a mask material, have wide applications in drug delivery and cosmetics. Electrospinning technology stands out among various nanofiber preparation technologies due to its ease of operation and low cost. Specifically, coaxial nanofibers prepared using needle- or needle-free coaxial electrospinning technology can encapsulate active molecules in the core layer, slowing down the burst release of active ingredients and protecting their activity from environmental degradation. This also reduces the widespread use of harmful ingredients such as preservatives and antioxidants in current cosmetic products.

[0004] Iron and zinc ions can improve the elasticity and resilience of skin and mucous membranes, making them more delicate and smooth. However, the hydrophilicity of zinc and iron nitrates makes them prone to burst release when applied to the skin. In previous studies, direct blending of zinc and iron phosphates often resulted in particle aggregation, uneven distribution of phosphate particles, low loading rate, and no good skin care effect.

[0005] Therefore, it is of great significance to develop a nanofiber mask with good dual sustained-release effect that can effectively improve skin condition. Summary of the Invention

[0006] To address the aforementioned problems, the first objective of this invention is to provide a method for preparing a dual-release nanofiber membrane. This preparation method is simple, has low production costs, and is easily mass-produced.

[0007] The second objective of this invention is to provide a dual-release nanofiber membrane prepared using the method described above. This dual-release nanofiber membrane achieves sustained release of active molecules from the core layer through a shell-core structure prepared using coaxial electrospinning technology, preventing burst release of active molecules and protecting its activity from environmental degradation without the need for preservatives or stabilizers. Simultaneously, it utilizes interfacial effects and anion exchange to prepare metal phosphate nanoaggregates, achieving a dual-release effect and further improving skin condition.

[0008] The third objective of this invention is to provide an application of the aforementioned dual-release nanofiber membrane in the preparation of sustained-release drugs and cosmetic products.

[0009] In this invention, the entire surface of a single fiber is decomposed, and each tiny region capable of undergoing the same deformation is considered a simple part, which can be called a finite element region.

[0010] To achieve the first objective mentioned above, the present invention adopts the following technical solution:

[0011] This invention discloses a method for preparing a dual-release nanofiber membrane, comprising the following steps:

[0012] S1. Dissolve the functional molecules in a solution containing a hydrophobic polymer compound to obtain a core spinning precursor solution.

[0013] S2. Dissolve the metal nitrate in a solution containing a hydrophilic polymer compound to obtain a shell spinning precursor solution;

[0014] S3. The core spinning precursor solution described in step S1 and the shell spinning precursor solution described in step S2 are coaxially electrospun, and a nanofiber membrane with a metal nitrate coaxial nanostructure is obtained by means of the interface effect.

[0015] S4. Immerse the nanofiber membrane prepared in step S3 into a phosphate solution to undergo an anion exchange reaction and obtain a dual-release nanofiber membrane with a metal phosphate coaxial nanostructure.

[0016] In this invention, the shell-core structure prepared by coaxial electrospinning technology enables the continuous release of active molecules in the core layer, preventing burst release behavior of active molecules, which is beneficial for the skin's absorption of active ingredients and improves facial condition. Furthermore, the light- and oxygen-barrier area formed within the shell layer effectively prevents active molecules from being oxidized by oxygen and degraded by light during shelf life without the addition of preservatives or stabilizers. This minimizes the time for active molecules to be oxidized and degraded, thus protecting the active ingredients and allowing them to fully act on the skin. Simultaneously, the inventors cleverly utilized interface effects and anion exchange to obtain a coaxial nanostructure with metal phosphates that also has the ability to continuously release metal ions. Moreover, the nanoaggregates have small particle sizes and good dispersion uniformity, which further improves skin condition, enhances the elasticity and resilience of the skin and mucous membranes, making them more delicate and smooth.

[0017] During the spinning process, as the high voltage electrostatic charge increases, the core layer solution and the shell layer solution are pulled out together from the spinneret droplet, forming a dynamic jet. As the jet is pulled towards the receiver by the electric field, the core layer solution evaporates with the solvent, and the inner layer jet is stretched and dried to form nanofibers. Meanwhile, the shell layer jet, attached to the core layer jet, experiences solvent evaporation. Due to the difference in hydrophilicity and hydrophobicity between the core and shell layer solutions, an interface forms between them. On one hand, the shell layer solution has a smaller proportion, resulting in a thinner coating layer; on the other hand, as the core and shell layer solvents evaporate, the hydrophilic / hydrophobic interface effect makes the interfacial stratification between the shell and core layer jets increasingly pronounced. The coating between the two then causes the shell layer to adhere to the core layer, completing the forming process. As the solvent evaporates, when the shell solution is insufficient to cover the entire core layer, the interfacial effect (interfacial stratification) causes it to agglomerate within the finite element region, adhering to the core layer and forming a coaxial metal nitrate nanostructure. (The fiber forming process is extremely fast, almost instantaneous. During this process, the shell solution is insufficient to cause large-area agglomeration, so it will self-agglomerate within the finite element region on the surface of the core fiber, forming a relatively uniformly distributed nanostructure.) Then, by immersing it in a phosphate solution, a metal phosphate coaxial nanostructure with low solubility is generated through anion exchange reaction, exhibiting a significant slow-release effect.

[0018] Furthermore, during coaxial electrospinning, the flow rate of the core layer spinning precursor solution is 0.3-1.5 ml / h, the flow rate of the shell layer spinning precursor solution is 0.1-0.5 ml / h, the spinning distance is 10-20 cm, the voltage is 13-20 kV, the temperature is 18-25℃, the humidity is 30-40%, and the drum speed is 200 r / min.

[0019] While experimenting with adding metal components to enhance the mask's effectiveness, the inventors discovered that during the spinning process, directly generating coaxial metal nitrate nanostructures without anion exchange resulted in a sudden release of the metal components in the mask. Conversely, directly generating coaxial metal phosphate nanostructures during spinning led to severe agglomeration, resulting in dispersion uniformity that did not meet application requirements. Therefore, the inventors utilized interfacial effects to first form coaxial metal nitrate nanostructures, and then used anion exchange to convert them into coaxial metal phosphate nanostructures. This not only achieved continuous release of metal ions but also mitigated agglomeration to some extent. The inventors further refined the preparation process, undergoing extensive... Quantitative experimental studies revealed that when the shell layer flow rate is greater than or close to the core layer flow rate, the interface effect easily forms a coating, but the metal nitrate coaxial nanostructure cannot be formed. When the shell layer flow rate is much less than the core layer flow rate, it affects the spinning stability and the dispersion uniformity of the metal nitrate coaxial nanostructure. Only when the core layer flow rate is slightly greater than the shell layer flow rate is it conducive to the microscopic finite element aggregation of the metal salt. Preferably, the flow rate of the core layer spinning precursor solution is 0.3-0.6 ml / h, and the flow rate of the shell layer spinning precursor solution is 0.1-0.2 ml / h. More preferably, the dispersion effect is best when the flow rate ratio of the core layer spinning precursor solution to the shell layer spinning precursor solution is 2.5-3.5:1.

[0020] Furthermore, the concentration of the hydrophobic polymer compound in the core spinning precursor solution is 2-20 wt%; exemplaryly, the concentration of the hydrophobic polymer compound in the core spinning precursor solution can also be 2-15 wt%, 2-10 wt%, 2-5 wt%, 5-20 wt%, 5-15 wt%, 5-10 wt%, 10-20 wt%, 10-15 wt%, 15-20 wt%, etc.

[0021] Furthermore, the amount of the active ingredient added is 0.5-5 wt% of the hydrophobic polymer compound; for example, the amount of the active ingredient added is 0.5 wt%, 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, 5 wt%, etc. of the hydrophobic polymer compound.

[0022] Furthermore, the concentration of the hydrophilic polymer in the shell spinning precursor solution is 2-20 wt%; exemplarily, the concentration of the hydrophobic polymer in the shell spinning precursor solution can also be 2-15 wt%, 2-10 wt%, 2-5 wt%, 5-20 wt%, 5-15 wt%, 5-10 wt%, 10-20 wt%, 10-15 wt%, 15-20 wt%, etc.

[0023] Furthermore, the amount of metal nitrate added is 0.5-5 wt% of the hydrophobic polymer compound; for example, the amount of metal nitrate added is 0.5 wt%, 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, 5 wt%, etc. of the hydrophobic polymer compound.

[0024] Furthermore, in step S4, the anion exchange reaction takes 10-60 minutes.

[0025] Furthermore, the hydrophobic polymeric compound includes, but is not limited to, one or two of polycaprolactone or polylactic acid; preferably, the active ingredient is a chemical component that is easily oxidized, including but not limited to one or more of amino acids, vitamin B2, hyaluronic acid, squalane, tranexamic acid, arbutin, and nicotinamide, and may also be vitamin C, vitamin E, pyridoxine dipalmitate, kojic acid palmitate, sodium ascorbate phosphate, magnesium ascorbate phosphate, ascorbate glucoside, 3-O-ethoxyascorbic acid, ascorbate palmitate, ascorbate tetraisocyanate palmitate, vitamin A, vitamin A acetate, ginkgo extract, resveratrol, ceramide, ginseng root extract, puerarin, riboflavin, vitamin B6, vitamin B6 dipalmitate, etc.

[0026] Furthermore, the hydrophilic polymer compound includes, but is not limited to, one or more of gelatin, polyvinyl alcohol, and polyvinylpyrrolidone.

[0027] Furthermore, the metal nitrates include, but are not limited to, one or more of ferric nitrate and zinc nitrate; they can also be salt compounds of other metals, and the metal phosphates include, but are not limited to, one or more of ferric phosphate and zinc phosphate. It should be noted that the above-mentioned anion exchange reaction can refer to precipitation-dissolution equilibrium. That is, when strong acid salts such as metal nitrates, metal sulfates, and metal hydrochlorides are selected in the shell material, they can be impregnated into solutions of medium-strong or weak acid salts to carry out anion exchange and form metal salt nano-aggregates with low solubility. The selected medium-strong or weak acid salts can be phosphates (e.g., diammonium hydrogen phosphate), oxalates (e.g., ammonium oxalate), carbonates (e.g., sodium carbonate, ammonium bicarbonate), etc.

[0028] Furthermore, the concentration of the impregnation solution (such as a phosphate solution) is 0.02-0.6 wt%; exemplaryly, the concentration of the impregnation solution may be 0.02 wt%, 0.04 wt%, 0.06 wt%, 0.08 wt%, 0.1 wt%, 0.15 wt%, 0.2 wt%, 0.25 wt%, 0.3 wt%, 0.35 wt%, 0.4 wt%, 0.45 wt%, 0.5 wt%, 0.55 wt%, 0.6 wt%, etc.

[0029] To achieve the second objective mentioned above, the present invention adopts the following technical solution:

[0030] This invention discloses a dual-release nanofiber membrane, which is prepared by the method described above.

[0031] Furthermore, the metal phosphate coaxial nanostructure is a metal phosphate nanoaggregate, and the particle size of the metal phosphate nanoaggregate is 20-190 nm; for example, the particle size of the metal phosphate nanoaggregate can be 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, etc., or any range formed by any two of these values.

[0032] Furthermore, the dispersion uniformity of the metal phosphate nanoaggregates is 2-26 particles / 100 nanometers square. Exemplarily, the dispersion uniformity of the metal phosphate nanoaggregates can also be 2-20 particles / 100 nanometers square, 2-15 particles / 100 nanometers square, 2-10 particles / 100 nanometers square, 2-5 particles / 100 nanometers square, 5-25 particles / 100 nanometers square, 5-20 particles / 100 nanometers square, 5-15 particles / 100 nanometers square, 5-10 particles / 100 nanometers square, 10-25 particles / 100 nanometers square, 10-20 particles / 100 nanometers square, 10-15 particles / 100 nanometers square, etc.

[0033] To achieve the third objective mentioned above, this invention discloses the application of the aforementioned dual-release nanofiber membrane in the preparation of sustained-release drugs and cosmetic products.

[0034] Furthermore, the cosmetic products include slow-release face masks, slow-release eye masks, slow-release neck masks, slow-release nasolabial fold masks, slow-release cheek wrinkle masks, or slow-release forehead wrinkle masks.

[0035] The aforementioned dual-release nanofiber membrane can be a solid mask. The usage method includes the following steps: After washing your face, moisten your skin with purified water or a spray, apply the mask to your face, and then replenish moisture to moisten your face as needed. Make the mask adhere to your face, massage to absorb, wait 15-20 minutes, then remove the mask and wash your face.

[0036] The beneficial effects of this invention are as follows:

[0037] This invention discloses a dual-release nanofiber membrane, its preparation and application, which has the following advantages:

[0038] 1. The dual-release nanofiber membrane provided by this invention has a large specific surface area and high porosity. It uses coaxial electrospinning technology to protect the activity of the active ingredients in the core layer. The shell layer generates hydrophobic nanoparticles of iron phosphate and zinc phosphate through interface effect and anion replacement, realizing the continuous release of zinc and iron ions, which is conducive to the skin's absorption of the active ingredients and improves the facial condition.

[0039] 2. From the perspective of the formation mechanism, the dual-release nanofiber membrane provided by this invention is based on the fact that the polymer solutions used in the core layer and shell layer are hydrophobic and hydrophilic polymers, so that a significant interface effect occurs during fiber formation; and the setting of the flow rate of the core layer and shell layer is more conducive to the microscopic finite element aggregation of the shell layer polymer and zinc-iron; the combined effect of the above two factors promotes the encapsulation of functional molecules in the core layer and the generation of coaxial nanofibers with zinc-iron salt nanoaggregates in the shell layer through the interface effect.

[0040] 3. The composite fiber structure provided by this invention, after subsequent anion exchange, generates more stable zinc-iron phosphate nanoaggregates. However, it differs from ordinary particle deposition, which leads to uneven dispersion of particles or aggregates (steric hindrance issues); and also from composite structures formed by layer-by-layer self-assembly (concentration gradient issues). Its dispersion uniformity is determined by the finite element aggregation at the interface, and the amount of zinc-iron cations determines its size, resulting in more uniform dispersion, more controllable size, and a more significant sustained-release effect. Furthermore, unlike the release of conventional particles or water-soluble metal salts, nanoscale particles more easily achieve particle wetting and controlled release.

[0041] 4. The dual-release fiber mask of the present invention is a dry mask, which is easy to store and convenient to use.

[0042] 5. The dual-release fiber mask of the present invention can simultaneously achieve the continuous release of multiple active ingredients, and through synergistic effect, improve the skin moisturizing and repairing effects.

[0043] 6. The preparation method of the dual-release fiber mask provided by the present invention is simple, has low production cost, and is easy to mass-produce. Attached Figure Description

[0044] The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0045] Figure 1 This is a SEM image of the nanofiber membrane before surface treatment in step 3 of Example 1.

[0046] Figure 2 This is a diameter distribution diagram of the nanofiber membrane before surface treatment in step 3 of Example 1;

[0047] Figure 3This is a TEM image of the nanofiber membrane before surface treatment in step 3 of Example 1;

[0048] Figure 4 This is a SEM image of the nanofiber surface after the nanofiber membrane is immersed in the phosphate solution in step 5 of Example 1.

[0049] Figure 5 The release curves of vitamin B2 within 30 min are shown in the samples prepared in Examples 1, 2 and Comparative Examples 1-3.

[0050] Figure 6 The release curves of iron ions in the samples prepared in Examples 1 and 2 and Comparative Examples 1 and 3 within 30 min are shown.

[0051] Figure 7 The release curves of zinc ions in the samples prepared in Examples 1 and 2 and Comparative Examples 1 and 3 within 30 min are shown. Detailed Implementation

[0052] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments and accompanying drawings, further explains the invention. Similar components in the drawings are indicated by the same reference numerals. Those skilled in the art should understand that the specific description below is illustrative rather than restrictive and should not be construed as limiting the scope of protection of the present invention.

[0053] Unless otherwise specified, all raw materials used in this invention are commercially available. Any range described in this invention includes end values, any values ​​between end values, and any sub-ranges formed by end values ​​or any values ​​between end values. Unless otherwise specified, all percentages are mass percentages.

[0054] Example 1

[0055] The raw materials and their mass percentages for the dual-release nanofiber mask prepared in Example 1 are as follows:

[0056] S1. Weigh 1g of polycaprolactone and dissolve it in 10ml of trifluoroethanol solution, stirring for 24h. Then weigh 0.05g of vitamin B2 and add it to the above solution, continuing to stir for 6h. This solution is used as a precursor solution for core spinning.

[0057] S2. Weigh 0.05g zinc nitrate and 0.05g ferric nitrate and dissolve them in 2ml deionized water. Then weigh 1g gelatin and dissolve it in 8ml trifluoroethanol. Mix and stir with the above solution for 6 hours to prepare the shell spinning precursor solution for later use.

[0058] S3. Using electrospinning technology, coaxial electrospinning is performed to prepare nanofiber membranes with a shell-core structure. The conditions for coaxial electrospinning are: core flow rate of 0.3 ml / h, shell flow rate of 0.1 ml / h, working voltage of 18 kV, working distance of 15 cm, roller speed of 200 r / min, ambient temperature of 18-25℃, and humidity of 30-40%.

[0059] S4. Weigh 0.006g of diammonium hydrogen phosphate and dissolve it in 10ml of water / ethanol (volume ratio 2 / 8) solution for later use.

[0060] S5. Then, the obtained nanofiber membrane is immersed in diammonium hydrogen phosphate solution for 10 minutes, then taken out, rinsed with ethanol, freeze-dried, sterilized by electron beam irradiation with an irradiation dose of 15 KGy, and vacuum-packed to obtain a double sustained-release nanofiber membrane.

[0061] Morphology characterization: The morphology of the nanofibers prepared in Experiment Example 1 was tested using scanning electron microscopy and transmission electron microscopy.

[0062] Conclusion: Figure 1 As shown, the shell-core structured nanofiber membrane prepared in step S3 of Example 1 has a smooth surface. ImageJ was used to statistically analyze the diameter distribution of the nanofibers, and the average diameter was 1.13 ± 0.16 μm. The results are as follows. Figure 2 As shown. Figure 3 This demonstrates that the nanofiber membrane possesses a core-shell structure. For example... Figure 4 As shown, after soaking in phosphate solution, nanoparticles are generated on the surface of nanofibers with an average particle size of 65 nm and a dispersion uniformity of 14 particles / 100 nm square.

[0063] Example 2

[0064] The raw materials and their mass percentages for the dual-release nanofiber mask prepared in Example 2 are as follows:

[0065] S1. Weigh 1g of polylactic acid and dissolve it in 10ml of chloroform / DMF (volume ratio 8:2) solution, and stir for 24h. Then weigh 0.05g of vitamin B2 and add it to the above solution, and continue stirring for 6h. This solution is used as a precursor solution for core layer spinning.

[0066] S2. Weigh 0.05g zinc nitrate and 0.05g ferric nitrate and dissolve them in 2ml deionized water. Then weigh 1g gelatin and dissolve it in 8ml trifluoroethanol. Mix and stir with the above solution for 6 hours to prepare the shell spinning precursor solution for later use.

[0067] S3. Using electrospinning technology, coaxial electrospinning is performed to prepare nanofiber membranes with a shell-core structure. The conditions for coaxial electrospinning are: core flow rate of 0.26 ml / h, shell flow rate of 0.1 ml / h, working voltage of 18 kV, working distance of 15 cm, roller speed of 200 r / min, ambient temperature of 18-25℃, and humidity of 30-40%.

[0068] S4. Weigh 0.006g of diammonium hydrogen phosphate and dissolve it in 10ml of water / ethanol (volume ratio 2 / 8) solution for later use.

[0069] S5. Then, the obtained nanofiber membrane is immersed in diammonium hydrogen phosphate solution for 10 minutes, then taken out, rinsed with ethanol, freeze-dried, sterilized by electron beam irradiation with an irradiation dose of 15 KGy, and vacuum-packed to obtain a double sustained-release nanofiber membrane.

[0070] Comparative Example 1

[0071] The raw materials and their mass percentages for the sustained-release nanofiber mask prepared in Comparative Example 1 are as follows:

[0072] S1. Weigh 1g of polycaprolactone and dissolve it in 10ml of trifluoroethanol solution, stirring for 24h. Then weigh 0.05g of vitamin B2 and add it to the above solution, continuing to stir for 6h. This solution is used as a precursor solution for core spinning.

[0073] S2. Weigh 0.05g zinc nitrate and 0.05g ferric nitrate and dissolve them in 2ml deionized water. Then weigh 1g gelatin and dissolve it in 8ml trifluoroethanol. Mix and stir with the above solution for 6 hours to prepare the shell spinning precursor solution for later use.

[0074] S3. Using electrospinning technology, coaxial electrospinning is performed to prepare nanofiber membranes with a shell-core structure. The conditions for coaxial electrospinning are: core flow rate of 0.3 ml / h, shell flow rate of 0.1 ml / h, working voltage of 18 kV, working distance of 15 cm, roller speed of 200 r / min, ambient temperature of 18-25℃, and humidity of 30-40%.

[0075] S4. After that, the nanofiber membrane is ventilated and placed for 48 hours for later use. It is then sterilized by electron beam irradiation with an irradiation dose of 15 kJ and vacuum packaged.

[0076] Comparative Example 2

[0077] The raw materials and their mass percentages for the sustained-release nanofiber mask prepared in Comparative Example 2 are as follows:

[0078] S1. Weigh 1g of polycaprolactone and dissolve it in 10ml of trifluoroethanol solution, stirring for 24 hours. Then weigh 0.05g of vitamin B2 and add it to the above solution, continuing to stir for 6 hours. This solution is then ready for use as a spinning solution.

[0079] S2. It adopts single-needle electrospinning technology, with a flow rate of 0.4ml / h, a working voltage of 18kv, a working distance of 15cm, a roller speed of 200r / min, an ambient temperature of 18-25℃, and a humidity of 30-40%.

[0080] S3. Allow the fiber to ventilate for 48 hours for later use, then sterilize it with electron beam irradiation at a dose of 15 KGy, and vacuum pack it.

[0081] Comparative Example 3

[0082] The raw materials and their mass percentages for the dual-slow-release nanofiber mask prepared in Comparative Example 3 are as follows:

[0083] S1. Weigh 1g of polycaprolactone and dissolve it in 10ml of trifluoroethanol solution, stirring for 24h. Then weigh 0.05g of vitamin B2 and add it to the above solution, continuing to stir for 6h. This solution is used as a precursor solution for core spinning.

[0084] S2. Weigh 0.05g zinc nitrate and 0.05g ferric nitrate and dissolve them in 2ml deionized water. Then weigh 1g gelatin and dissolve it in 8ml trifluoroethanol. Mix and stir with the above solution for 6 hours to prepare the shell spinning precursor solution for later use.

[0085] S3. Using electrospinning technology, coaxial electrospinning is performed to prepare nanofiber membranes with a shell-core structure. The conditions for coaxial electrospinning are: core flow rate of 0.4 ml / h, shell flow rate of 0.1 ml / h, working voltage of 18 kV, working distance of 15 cm, roller speed of 200 r / min, ambient temperature of 18-25℃, and humidity of 30-40%.

[0086] S4. Weigh 0.006g of diammonium hydrogen phosphate and dissolve it in 10ml of water / ethanol (volume ratio 2 / 8) solution for later use.

[0087] S5. Then, the obtained nanofiber membrane is immersed in diammonium hydrogen phosphate solution for 10 minutes, then taken out, rinsed with ethanol, freeze-dried, sterilized by electron beam irradiation with an irradiation dose of 15 KGy, and vacuum-packed to obtain a double sustained-release nanofiber membrane.

[0088] Comparative Example 4

[0089] The raw materials and their mass percentages for the dual-slow-release nanofiber mask prepared in Comparative Example 4 are as follows:

[0090] S1. Weigh 1g of polycaprolactone and dissolve it in 10ml of trifluoroethanol solution, stirring for 24h. Then weigh 0.05g of vitamin B2 and add it to the above solution, continuing to stir for 6h. This solution is used as a precursor solution for core spinning.

[0091] S2. Weigh 0.05g zinc nitrate and 0.05g ferric nitrate and dissolve them in 2ml deionized water. Then weigh 1g gelatin and dissolve it in 8ml trifluoroethanol. Mix and stir with the above solution for 6 hours to prepare the shell spinning precursor solution for later use.

[0092] S3. Using electrospinning technology, coaxial electrospinning is performed to prepare nanofiber membranes with a shell-core structure. The conditions for coaxial electrospinning are: core flow rate of 0.1 ml / h, shell flow rate of 0.1 ml / h, working voltage of 18 kV, working distance of 15 cm, roller speed of 200 r / min, ambient temperature of 18-25℃, and humidity of 30-40%.

[0093] S4. Weigh 0.006g of diammonium hydrogen phosphate and dissolve it in 10ml of water / ethanol (volume ratio 2 / 8) solution for later use.

[0094] S5. Then, the obtained nanofiber membrane is immersed in diammonium hydrogen phosphate solution for 10 minutes, then taken out, rinsed with ethanol, freeze-dried, sterilized by electron beam irradiation with an irradiation dose of 15 KGy, and vacuum-packed to obtain a double sustained-release nanofiber membrane.

[0095] Conclusion: When the core-shell flow rate ratio is 1:1, due to the relatively large liquid supply to the shell layer, it directly forms a thin film that encapsulates the fibers formed in the core layer, generating a conventional core-shell structure fiber (core layer fiber, shell layer film), rather than forming a dual-release nanofiber membrane with a metal phosphate coaxial nanostructure. Therefore, our dual-release design requirement cannot be achieved.

[0096] Experimental Example 1

[0097] Active component release experiment

[0098] Examples 1-2 and Comparative Examples 1-3 were selected as samples. 20 mg of each sample was accurately weighed and placed in a 10 ml centrifuge tube containing 5 ml of aqueous solution (pH=6, weakly acidic). The centrifuge tube was placed in a 37°C constant temperature shaking incubator at 60 rpm. At 2 min, 4 min, 6 min, 8 min, 12 min, 16 min, 20 min, and 30 min, 3 ml of solution was accurately pipetted and replenished with 3 ml of fresh aqueous solution (pH=6, weakly acidic). The absorbance of the pipetted solution at 475 nm (the characteristic UV absorption peak of vitamin B2) was measured. This 3 ml solution was then recovered, diluted 5 times, and the concentration of zinc and iron ions was determined using inductively coupled plasma atomic emission spectrometry (ICP-AES). Finally, a curve showing the release rate of the active ingredient versus time was plotted. (See attached diagram). Figures 5-7 .

[0099] like Figure 5 , 6As shown in Figures 7 and 8, the dual-release nanofiber masks in Examples 1-2 exhibited good sustained-release effects on vitamin B2 and zinc and iron ions. In Comparative Example 1, because no hydrophobic zinc phosphate and iron phosphate nanoparticles were generated on the surface, the hydrophilic zinc and iron ions in the shell were released rapidly, and the vitamin B2 in the core layer was also released more quickly due to the weakened barrier effect of the outer layer. In Comparative Example 2, due to the use of single-needle electrospinning and the lack of shell protection, vitamin B2 experienced a burst release. In Comparative Example 3, because the supply of shell solution per unit time was too small during the spinning process, the amount of shell solution accumulating in the finite element region on the surface of the core fiber was too small, resulting in small and irregular zinc phosphate and iron phosphate nanoparticles. Therefore, this led to the rapid release of zinc and iron particles. The accelerated disintegration rate of particles on the fiber surface also led to the rapid release of vitamin B2 from the core layer. This rapid release is detrimental to skin absorption.

[0100] Experimental Example 2

[0101] Moisturizing function test experiment

[0102] Based on the principle of voluntariness, 60 volunteers with an average age between 20 and 40 years old were selected, 30 men and 30 women. All of them had sunburned faces and were randomly divided into 4 groups, using the masks of Examples 1 and 2 and Comparative Examples 1-3 respectively.

[0103] Subjects were required not to use other products of the same type during the experiment, and no skin allergies, erythema, itching, or other adverse reactions occurred due to the use of the test samples. Before the test, subjects cleansed their faces and applied the masks prepared in the embodiments and comparative examples of this invention to their left cheeks as the experimental group. A non-woven fabric soaked in deionized water was applied to their right cheeks as the control group. After 15 minutes, the masks were removed, the faces were washed with water, and dried before the test. The test period lasted for 4 weeks, and the skin condition of the same areas on the left and right cheeks of the volunteers was tested using an Antera 3D instrument.

[0104] Table 1. Test data on skin change ratio before and after use.

[0105] Skin hemoglobin content stratum corneum moisture content Transepidermal water loss Example 1 80％ 87％ 70％ Example 2 83％ 86％ 73％ Comparative Example 1 42％ 46％ 45％ Comparative Example 2 35％ 41％ 40％ Comparative Example 3 57％ 66％ 63％

[0106] The test results are shown in Table 1. Compared with Comparative Examples 1-3, the test values ​​of the stratum corneum moisture content of the subjects' skin were significantly increased, while the test values ​​of transepidermal water loss rate and skin hemoglobin content were significantly reduced when using the masks of Examples 1-2. This indicates that the prepared dual-release nanofiber mask has good moisturizing and water-locking effects and soothing effects.

[0107] Experimental Example 3

[0108] Skin elasticity test experiment

[0109] Sixty female volunteers with an average age between 30 and 50 years old were selected. The masks from Examples 1 and 2, and Comparative Examples 1-3 were distributed to the participants. The participants were divided into four groups of 15 people each. Each group used a specific type of mask. Skin elasticity was tested using a skin analyzer before use, 15 days after use, and 30 days after use. The higher the value of the elastic stretch, the better the skin elasticity.

[0110] Table 2. Skin elasticity test data before and after use.

[0111] sample Before use After 15 days of use After 30 days of use Example 1 0.322 0.441 0.607 Example 2 0.314 0.437 0.599 Comparative Example 1 0.330 0.387 0.424 Comparative Example 2 0.318 0.345 0.379 Comparative Example 3 0.321 0.401 0.497

[0112] As shown in Table 2, the test results show that the skin elasticity of the subjects using the mask of the present invention was significantly improved; however, the sustained release and absorption of the mask without the formation of iron and zinc nanoparticles were poor, and the improvement on the skin was not obvious; Comparative Example 2, which did not consider the loading of trace elements such as iron and zinc, had the worst effect on skin elasticity; Comparative Example 3, which had small and irregular zinc and iron nanoparticles on the surface, also did not have an ideal effect on improving skin elasticity.

[0113] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all the implementation methods here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A method for preparing a dual-release nanofiber membrane, characterized in that, Includes the following steps: S1. Dissolve the functional molecules in a solution containing a hydrophobic polymer compound to obtain a core spinning precursor solution. S2. Dissolve the metal nitrate in a solution containing a hydrophilic polymer compound to obtain a shell spinning precursor solution; S3. The core spinning precursor solution described in step S1 and the shell spinning precursor solution described in step S2 are coaxially electrospun, and a nanofiber membrane with a metal nitrate coaxial nanostructure is obtained by means of the interface effect. S4. Immerse the nanofiber membrane prepared in step S3 into a phosphate solution to undergo an anion exchange reaction to obtain a dual-release nanofiber membrane with a metal phosphate coaxial nanostructure. During coaxial electrospinning, the flow rate of the core layer spinning precursor solution is 0.3-1.5 ml / h, the flow rate of the shell layer spinning precursor solution is 0.1-0.5 ml / h, the spinning distance is 10-20 cm, the voltage is 13-20 kV, the temperature is 18-25℃, the humidity is 30-40%, and the drum speed is 200 r / min. The flow rate ratio of the core spinning precursor solution to the shell spinning precursor solution is 2.5-3.5:1; The concentration of hydrophobic polymer compounds in the core spinning precursor solution is 2-20 wt%. The amount of the metal nitrate added is 0.5-5 wt% of the hydrophobic polymer compound; The concentration of the phosphate solution is 0.02-0.6 wt%.

2. The preparation method according to claim 1, characterized in that, The flow rate of the core spinning precursor solution is 0.3-0.6 ml / h, and the flow rate of the shell spinning precursor solution is 0.1-0.2 ml / h.

3. The preparation method according to claim 1, characterized in that, The amount of the functional molecule added is 0.5-5 wt% of the hydrophobic polymer compound.

4. The preparation method according to claim 1, characterized in that, The concentration of the hydrophilic polymer compound in the shell spinning precursor solution is 2-20 wt%.

5. The preparation method according to claim 1, characterized in that, In step S4, the anion exchange reaction takes 10-60 minutes.

6. The preparation method according to claim 1, characterized in that, The hydrophobic polymeric compound includes one or both of polycaprolactone or polylactic acid.

7. The preparation method according to claim 1, characterized in that, The active ingredients include one or more of the following: amino acids, vitamin B2, hyaluronic acid, squalane, tranexamic acid, arbutin, and nicotinamide.

8. The preparation method according to claim 1, characterized in that, The hydrophilic polymeric compound includes one or more of gelatin, polyvinyl alcohol, and polyvinylpyrrolidone.

9. The preparation method according to claim 1, characterized in that, The metal nitrate is selected from one or two of ferric nitrate and zinc nitrate.

10. The preparation method according to claim 1, characterized in that, The phosphate solution is a diammonium hydrogen phosphate solution.

11. The dual-release nanofiber membrane prepared by any one of the preparation methods described in claims 1-10.

12. The dual-release nanofiber membrane according to claim 11, characterized in that, The metal phosphate coaxial nanostructure is a metal phosphate nanoaggregate, and the particle size of the metal phosphate nanoaggregate is 20-190 nm.

13. The dual-release nanofiber membrane according to claim 11, characterized in that, The dispersion uniformity of the metal phosphate nanoaggregates is 2-26 particles / 100 nanometers square.

14. The application of a dual-release nanofiber membrane as described in any one of claims 11-13 in the preparation of sustained-release drugs and cosmetic products.

15. The application according to claim 14, characterized in that, The cosmetic products include slow-release face masks, slow-release eye masks, slow-release neck masks, slow-release nasolabial fold masks, slow-release cheek wrinkle masks, or slow-release forehead wrinkle masks.

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