Micro-current eye patch for fading dark circles and preparation method of micro-current eye patch

Abstract

The invention discloses a micro-current eye patch for fading dark circles and a preparation method of the micro-current eye patch, and relates to the technical field of eye care patches. The micro-current eye patch comprises a conducting layer and a liquid medicine layer located above the conducting layer, and the conducting layer is provided with electrodes. The liquid medicine layer is prepared from the following raw materials in percentage by mass: 76 to 84 percent of radix salviae miltiorrhizae extract, 0.072 to 0.089 percent of borneol, 1.98 to 2.18 percent of propylene glycol, 3.6 to 4.4 percent of glycerol, 0.75 to 0.94 percent of Tween, 0.0003 to 0.0015 percent of PEG-ZnO nanoparticles and the balance of normal saline. The PEG-ZnO nanoparticles are prepared by wrapping the outer part of ZnO nanoparticles with PEG (Polyethylene Glycol). According to the micro-current eye patch provided by the invention, through the mutual synergistic effect of the radix salviae miltiorrhizae extract and the PEG-ZnO nanoparticles, the electrical conductivity of liquid medicine and the skin permeation efficiency are improved, the medicine permeation efficiency is improved by 30-50%, and the local tissue medicine concentration is remarkably enhanced.

Description

Technical Field

[0001] The present invention relates to the technical field of eye care patches, and particularly to a microcurrent eye patch for lightening dark circles and a preparation method thereof. Background Art

[0002] The skin around the eyes of humans is distributed with very dense nerve fibers and capillaries. When the eyes are over-fatigued or damaged due to bad living habits (such as staying up late, long-term sun exposure, smoking, drinking, emotional distress, etc.), the skin around the eyes is likely to have congestion due to poor blood circulation, resulting in dullness and pigmentation of the skin around the eyes, and then forming dark circles. The incidence of dark circles is high, and it seriously affects the appearance and mental health of patients.

[0003] In order to lighten dark circles, a large number of eye mask patches with the function of removing dark circles have appeared on the market. Research shows that microcurrent stimulation can play a protective role in retinal neurons. When retinal nerve cells are damaged, providing microcurrent stimulation to them can promote the secretion of neurotrophic factors and repair damaged neurons; it can also soothe the eye muscles and activate the cellular immune activity. However, the drug conductivity of existing microcurrent drug delivery devices is relatively low, and only the effects of microcurrent or drugs are unidirectionally concerned. Moreover, the preparation method causes a large loss of conductive drug active ingredients, and the synergistic effect of microcurrent and drugs cannot be fully exerted, so there is still room for improvement in the effect of lightening dark circles. Summary of the Invention

[0004] The present invention provides a microcurrent eye patch for lightening dark circles and a preparation method thereof. By selecting salvia miltiorrhiza extract and borneol as raw materials and adding polyethylene glycol (PEG)-modified zinc oxide (ZnO) nanoparticles, through the synergistic effect of salvia miltiorrhiza extract and PEG-modified zinc oxide nanoparticles, not only the absorption of drugs by the skin is promoted, but also the charge transfer is promoted, the conductivity of the drug layer of the patch is enhanced, and the effect of lightening dark circles is significantly improved. Specifically, it is achieved through the following technologies.

[0005] A microcurrent eye patch for lightening dark circles, comprising a conductive layer and a liquid medicine layer located above the conductive layer, wherein a positive electrode and a negative electrode are provided on the conductive layer; the liquid medicine layer is composed of microcapsules filled with liquid medicine, and the raw materials of the liquid medicine include 76-84% of salvia miltiorrhiza extract, 0.072-0.089% of borneol, 1.98-2.18% of propylene glycol, 3.6-4.4% of glycerol, 0.75-0.94% of tween, 0.0003-0.0015% of PEG-ZnO nanoparticles by mass percentage, and the balance is normal saline;

[0006] The preparation method of the PEG-ZnO nanoparticles is as follows:

[0007] Mix an aqueous zinc salt solution with an excessive amount of alkali solution and stir to obtain a white suspension. Filter and wash the precipitate, heat and calcine it, and then add PEG and stir to dissolve. The mass ratio of the PEG to ZnO (the mass of ZnO can be theoretically calculated based on the hydrothermal reaction process of the zinc salt and the alkali solution) is 1:(5 - 10);

[0008] Perform a hydrothermal reaction at 170 - 190 °C for 5 - 10 h. During the reaction process, adjust the pH value of the reaction system to 9.5 - 10.5 to obtain a PEG-ZnO precursor;

[0009] Centrifuge to obtain the precipitate, disperse it in absolute ethanol, add a silane coupling agent with a dosage of 0.5 - 1% of the mass of ZnO (the mass of ZnO can be theoretically calculated based on the hydrothermal reaction process of the zinc salt and the alkali solution), and reflux at 50 - 70 °C for 1.5 - 3 h to obtain the PEG-ZnO nanoparticles.

[0010] Furthermore, in the preparation method of the PEG-ZnO nanoparticles, the conditions for the hydrothermal reaction are to react at 180 °C for 6 h.

[0011] Furthermore, in the preparation method of the PEG-ZnO nanoparticles, the reflux conditions after adding the silane coupling agent are to reflux at 60 °C for 2 h.

[0012] Optionally, in the above preparation method of the PEG-ZnO nanoparticles, the aqueous zinc salt solution can be selected from zinc nitrate (such as zinc nitrate, Zn(NO3)2), zinc sulfate (ZnSO4), zinc acetate (Zn(CH2COO)2), zinc chloride (ZnCl2), (Zn5(CO3)2(OH)6), etc., which are water-soluble zinc salts.

[0013] Optionally, in the above preparation method of the PEG-ZnO nanoparticles, the selected alkali solution can be sodium hydroxide (NaOH) solution, potassium hydroxide (KOH), ammonia water (NH3·H2O), urea (CO(NH2)2), etc. The concentration of these alkali solutions can be adjusted arbitrarily as long as it ensures that the pH value of the final reaction system is satisfied.

[0014] Optionally, in the above preparation method of the PEG-ZnO nanoparticles, the silane coupling agent can be selected from commercially available common types of products, such as silane coupling agent KH550 (3-aminopropyltriethoxysilane), KH560 (3-glycidoxypropyltrimethoxysilane), KH570 (3-methacryloxypropyltrimethoxysilane), KH792 (N-(β-aminoethyl)-γ-aminopropyltrimethoxysilane), MPTMS (3-mercaptopropyltrimethoxysilane), etc.

[0015] Among the raw materials of the microcurrent eye patch for lightening dark circles provided by the present invention, the polyethylene glycol for preparing PEG-ZnO nanoparticles can be selected from commercially available products with common molecular weights, such as those with molecular weights of 2000-5000 Da.

[0016] Further, the raw materials of the liquid medicine include 84% of salvia miltiorrhiza extract, 0.075% of borneol, 1.98% of propylene glycol, 4% of glycerol, 0.8% of tween, and 0.0015% of PEG-ZnO nanoparticles by mass percentage, and the rest is normal saline.

[0017] Further, the preparation method of the salvia miltiorrhiza extract is as follows: taking the medicinal material salvia miltiorrhiza and soaking it with normal saline; adding an ethanol solution to the mixture until the volume concentration of ethanol in the system is 30%, and standing at 4°C for 10-14 h to complete primary alcohol precipitation;

[0018] Adding ethanol (either ethanol solution or absolute ethanol) to the supernatant after primary alcohol precipitation until the volume concentration of ethanol in the system is 60%, and standing at 4°C for 5-7 h to complete secondary alcohol precipitation;

[0019] Adding ethanol (either ethanol solution or absolute ethanol) to the supernatant after secondary alcohol precipitation until the volume concentration of ethanol in the system is 80%, and standing at 4°C for 5-7 h to complete final alcohol precipitation;

[0020] Taking the supernatant after final alcohol precipitation and vacuum concentrating it at low temperature to a relative density of 1.15-1.20 at 25°C to obtain the salvia miltiorrhiza extract.

[0021] Further, a first non-woven fabric layer is provided below the conductive layer.

[0022] Furthermore, a skin-friendly adhesive layer is provided around the lower surface of the first non-woven fabric layer. In order to reserve the area for contacting the eyes, the skin-friendly adhesive layer is not provided in the middle of the lower surface of the first non-woven fabric layer.

[0023] Further, a breathable and waterproof cotton cloth layer is provided above the liquid medicine layer.

[0024] Furthermore, a second non-woven fabric layer is provided above the breathable and waterproof cotton cloth layer.

[0025] In order to provide a microcurrent eye patch that can lighten dark circles, the present invention selects salvia miltiorrhiza to prepare salvia miltiorrhiza extract, combines borneol as the active ingredient of the liquid medicine layer of the patch, and also adds PEG-ZnO nanoparticles to the liquid medicine layer.

[0026] The salvia miltiorrhiza extract has pharmacological effects of anti-inflammatory, antioxidant, promoting blood circulation to remove blood stasis, and promoting skin repair, and can lighten dark circles by targeting and improving microcirculation around the eyes. Borneol can promote drug absorption and help relieve symptoms such as inflammation or poor blood circulation around the eyes.

[0027] In addition to combining the above-mentioned effects of danshen and borneol, by jointly applying the danshen extract and PEG-ZnO nanoparticles, compared with using the danshen extract alone or using PEG-ZnO nanoparticles alone, the drug conductivity of the eye patch is significantly improved, and the drug introduction efficiency is greatly enhanced.

[0028] In the present invention, the liquid medicine is encapsulated in microcapsules. When in use, the microcapsules are squeezed to rupture the wall material, and the contained liquid medicine is released to the primary battery layer, causing the printed primary battery to conduct and discharge, and forming a microcurrent between the eye patch and the eye skin. The charged danshen extract and borneol liquid medicine ions penetrate the skin tissue barrier and enter the human body under the action of the microcurrent. The microcurrent simultaneously stimulates the local tissue cell metabolism of the eyes, promotes blood circulation, and relaxes the spasm of the eye muscle groups around the eyes. Its physical effect synergizes with the pharmacological effect of the danshen liquid medicine to enhance the effect of dark circle fading from multiple channels.

[0029] Optionally, the conductive layer provided by the present invention is generally prepared by printing positive and negative electrode pastes on medical flexible water-permeable materials such as non-woven fabric, polyurethane (PU) film, thermoplastic polyurethane (TPU), ePTFE film, polyester / nylon mesh cloth, etc. Its structure and preparation method are relatively mature technologies in the art, and there are a large number of commercially available products.

[0030] Optionally, the conductive layer provided by the present invention can be directly obtained by purchasing from the market.

[0031] Optionally, the conductive layer provided by the present invention can also be self-prepared by screen printing technology or the like, and the positive and negative electrodes are printed on the above-mentioned medical flexible water-permeable materials.

[0032] Optionally, the voltage of the conductive layer is 0.4 - 0.7 V, and the microcurrent is 0.35 - 0.71 mA.

[0033] The main function of the microcapsules selected when preparing the liquid medicine layer in the present invention is to encapsulate the danshen extract, borneol, and other liquid medicine components. Therefore, as long as it can meet the above requirements and is a pharmaceutically acceptable excipient, it can be used as the raw material of the microcapsules.

[0034] Optionally, the coating material of the microcapsules is poly(D,L-lactic acid-co-glycolic acid) or polyethylene glycol.

[0035] Optionally, the particle size of the microcapsules encapsulating the liquid medicine is 100 - 150 mesh.

[0036] As a preferred structure of the microcurrent eye patch provided by the present invention, in addition to setting a conductive layer and a liquid medicine layer, a first non-woven fabric layer can also be provided below the conductive layer.

[0037] Furthermore, a skin-friendly adhesive layer is provided around the lower surface of the first non-woven fabric layer. The coverage area of the skin-friendly adhesive layer can correspond to the area range in contact with the skin, and a part in contact with the eye skin should be reserved.

[0038] As a preferable structure of the microcurrent eye patch provided by the present invention, in addition to providing a conductive layer and a liquid medicine layer, a breathable and waterproof cotton cloth layer can also be provided above the liquid medicine layer.

[0039] Furthermore, a second non-woven fabric layer can also be provided above the breathable and waterproof cotton cloth layer.

[0040] As an optimal structure, the structure of the microcurrent eye patch provided by the present invention can adopt the above method, and at the same time, the above-mentioned first non-woven fabric layer, skin-friendly adhesive layer, breathable and waterproof cotton cloth layer and second non-woven fabric layer are provided.

[0041] The present invention also provides a preparation method of the microcurrent eye patch according to any one of the above, including the following steps:

[0042] Add borneol to propylene glycol and stir to dissolve, then add Tween and mix evenly, and then add the PEG-ZnO nanoparticles and mix evenly to obtain a mixed system; stir and mix the salvia miltiorrhiza extract, glycerol, the mixed system and physiological saline evenly, and adjust the pH value of the system to neutral to obtain the liquid medicine;

[0043] Encapsulate the liquid medicine with a microcapsule material to form microcapsules, and place them on the conductive layer.

[0044] In the preparation method of the microcurrent eye patch provided by the present invention, borneol is first dissolved in propylene glycol and Tween, the raw materials of the liquid medicine layer, to prepare a borneol solution, and then PEG-ZnO nanoparticles are added. This can further avoid the aggregation of PEG-ZnO nanoparticles and improve the stability of PEG-ZnO nanoparticles. If borneol, propylene glycol, Tween and PEG-ZnO nanoparticles are directly added together, it may affect the dissolution rate of borneol and the stability of the whole system.

[0045] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0046] 1. The present invention provides a salvia miltiorrhiza microcurrent eye patch for lightening dark circles under the eyes, and its raw materials are selected from salvia miltiorrhiza extract and nano-zinc oxide encapsulated with polyethylene glycol (PEG-ZnO nanoparticles). Encapsulating PEG on nano-zinc oxide can also improve the dispersibility of nano-zinc oxide and increase the effective conductive area.

[0047] The synergistic effect between the danshen extract and the PEG-ZnO nanoparticles can also promote charge transfer, further enhance the conductivity of the drug, and make its conductivity adapt to the requirements of microcurrent action (0.35 - 0.71 mA), ensuring the stable triggering of the electroosmotic effect and breaking through the bottleneck of the passive penetration efficiency of traditional eye patches.

[0048] 2. In the preparation method of the danshen microcurrent eye patch for lightening dark circles provided by the present invention, different components in the danshen medicinal liquid are extracted in stages (i.e., "gradient ethanol precipitation method") to obtain the final danshen extract, avoiding the destruction of charged active components by high-concentration ethanol at one time; the medicinal liquid is concentrated at a low temperature (50 - 60°C) in a vacuum environment, which can reduce the boiling point of the solution, reduce the risk of thermal decomposition, and also retain more conductive active components, improving the conductivity of the drug itself.

[0049] 3. Based on the composite structure of the conductive carrier layer and the medicinal liquid layer, the directional transdermal penetration of active components driven by microcurrent is realized in a closed circuit, enabling the drug penetration efficiency to be increased by 30 - 50% compared to the patch without microcurrent generation, and significantly enhancing the drug concentration in local tissues. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figure 1 It is a schematic structural diagram of the microcurrent eye patch provided by the present invention.

[0051] Figure 2 It is a schematic structural diagram (tilted upward view) of the first non-woven fabric layer (lower surface) and the skin-friendly adhesive layer in the microcurrent eye patch provided by the present invention.

[0052] In the figure: 1. Conductive layer; 2. Medicinal liquid layer; 3. First non-woven fabric layer; 4. Breathable and waterproof cotton cloth layer; 5. Second non-woven fabric layer; 6. Skin-friendly adhesive layer. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0053] The technical solutions of the present invention will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of them. All other embodiments obtained by those of ordinary skill in the art without creative efforts based on the embodiments of the present invention belong to the scope of protection of the present invention.

[0054] In some embodiments of the present invention, the microcurrent eye patch provided includes a conductive layer 1 and a medicinal liquid layer 2 located above the conductive layer 1. The conductive layer 1 is provided with positive and negative electrodes, and a first non-woven fabric layer 3 is further provided below the conductive layer 1; a breathable and waterproof cotton cloth layer 4 is provided above the medicinal liquid layer 2, and a second non-woven fabric layer 5 is provided above the breathable and waterproof cotton cloth layer 4. Figure 1 As shown, it includes a conductive layer 1 and a medicinal liquid layer 2 located above the conductive layer 1. The conductive layer 1 is provided with positive and negative electrodes, and a first non-woven fabric layer 3 is further provided below the conductive layer 1; a breathable and waterproof cotton cloth layer 4 is provided above the medicinal liquid layer 2, and a second non-woven fabric layer 5 is provided above the breathable and waterproof cotton cloth layer 4.

[0055] Furthermore, as shown in Figure 2As shown, a skin-friendly adhesive layer 6 is provided on the lower surface of the first non-woven fabric layer 3. The coverage area of the skin-friendly adhesive layer can correspond to the area range in contact with the skin. Generally, it is coated around the periphery, leaving an area in the middle for contact with the skin of the eyes.

[0056] The raw materials of the liquid medicine layer include, by mass percentage, 76 - 84% of salvia miltiorrhiza extract, 0.072 - 0.089% of borneol, 1.98 - 2.18% of propylene glycol, 3.6 - 4.4% of glycerol, 0.75 - 0.94% of tween, 0.0003 - 0.0015% of PEG-ZnO nanoparticles, and the balance is normal saline.

[0057] In some embodiments of the present invention, the preparation method of PEG-ZnO nanoparticles is as follows:

[0058] Mix and stir an aqueous zinc salt solution with an excessive amount of alkali solution to obtain a white suspension, and add 1 - 3% of PEG by total mass and stir to dissolve; optionally, the aqueous zinc salt solution is zinc nitrate (such as zinc nitrate hexahydrate, Zn(NO3)2·6H2O), zinc sulfate (ZnSO4·7H2O), zinc acetate (Zn(CH2COO)2·2H2O), zinc chloride (ZnCl2), (Zn5(CO3)2(OH)6), etc., which are water-soluble zinc salts; the alkali solution can be sodium hydroxide (NaOH) solution, potassium hydroxide (KOH), ammonia water (NH3·H2O), urea (CO(NH2)2), etc., and a commercially available common model of silane coupling agent can be selected, such as silane coupling agent KH550 (3-aminopropyltriethoxysilane), KH560 (3-glycidoxypropyltrimethoxysilane), KH570 (3-methacryloxypropyltrimethoxysilane), KH792 (N-(β-aminoethyl)-γ-aminopropyltrimethoxysilane), MPTMS (3-mercaptopropyltrimethoxysilane), etc.; polyethylene glycol can be selected from commercially available products with common molecular weights, such as those with a molecular weight of 2000 - 5000 Da.

[0059] Subject the above mixed system to hydrothermal reaction at 170 - 190 °C for 5 - 10 h, and adjust the pH value of the reaction system to 9.5 - 10.5 during the reaction process to obtain a PEG-ZnO precursor;

[0060] Centrifuge to obtain the precipitate, disperse it in absolute ethanol, add a silane coupling agent in an amount of 0.5 - 1% of the mass of ZnO, and reflux at 50 - 70 °C for 1.5 - 3 h to obtain the PEG-ZnO nanoparticles.

[0061] In some embodiments of the present invention, the preparation method of salvia miltiorrhiza extract is as follows:

[0062] Take the medicinal material Salvia miltiorrhiza, soak it with physiological saline (for example, the material-liquid ratio is 1:8 - 10 (kg:L)), then add 90% ethanol solution until the final volume concentration is 30%, and let it stand at 4°C for 12 h to complete the primary alcohol precipitation;

[0063] Centrifuge and take the supernatant after the primary alcohol precipitation, add ethanol (either ethanol solution or absolute ethanol) until the concentration is 60%, and let it stand at 4°C for 6 h to complete the primary alcohol precipitation;

[0064] Take the supernatant after the primary alcohol precipitation, add ethanol until the volume concentration of ethanol in the system is 60 - 65%, and let it stand at 4°C for 8 - 10 h to complete the secondary alcohol precipitation;

[0065] Take the supernatant after the secondary alcohol precipitation, add ethanol until the volume concentration of ethanol in the system is 80 - 85%, and let it stand at 4°C for 5 - 7 h to complete the final alcohol precipitation;

[0066] Take the supernatant after the final alcohol precipitation, and concentrate it under vacuum at low temperature to a relative density of 1.15 - 1.20 at 25°C to obtain the Salvia miltiorrhiza extract.

[0067] Example 1

[0068] For the microcurrent eye patch for lightening dark circles provided in this example, the raw materials of the liquid medicine layer include, by mass percentage: 84% of Salvia miltiorrhiza extract, 0.075% of borneol, 1.98% of propylene glycol, 4% of glycerol, 0.8% of Tween, 0.0015% of PEG-ZnO nanoparticles, and the rest is physiological saline.

[0069] After weighing the above raw materials according to the mass percentage, the preparation method of the microcurrent eye patch includes the following steps:

[0070] 1. Prepare Salvia miltiorrhiza extract

[0071] (1) Weigh 5 kg of Salvia miltiorrhiza medicinal material, crush it, add 40 L of physiological saline (material-liquid ratio 1:8 (kg:L)), and soak it at room temperature for 30 min;

[0072] (2) Perform gradient ethanol precipitation:

[0073] Primary alcohol precipitation: Add 90% ethanol to the mixture until the volume concentration of ethanol in the system is 30% (v / v), and let it stand at 4°C for 12 h;

[0074] Secondary alcohol precipitation: Take the supernatant after the primary alcohol precipitation, add ethanol until the volume concentration of ethanol in the system is 60%, and let it stand at 4°C for 8 h;

[0075] Final alcohol precipitation: Take the supernatant after the secondary alcohol precipitation, add ethanol until the volume concentration of ethanol in the system is 80%, and let it stand at 4°C for 6 h.

[0076] The supernatant after final alcohol precipitation is concentrated under vacuum at low temperature, with the temperature controlled at 45°C and the vacuum degree at -0.08 to -0.1 MPa, until the relative density reaches 1.15 - 1.20 (25°C), obtaining the Salvia miltiorrhiza extract.

[0077] 2. Preparation of borneol solution

[0078] Weigh borneol and grind it into powder, add propylene glycol and stir to dissolve, then add Tween 80 and mix evenly to obtain the borneol solution;

[0079] 3. Preparation of PEG-ZnO nanoparticles

[0080] (1) Mix the Zn(NO3)2 solution (0.1 mol / L) and the NaOH solution (0.2 mol / L) at a volume ratio of 1:2 (the NaOH solution is in excess), and stir magnetically at 500 rpm for 30 min to form a white suspension.

[0081] (2) Add PEG (molecular weight 3500 Da, accounting for 3% of the total mass of PEG-ZnO nanoparticles), and continue stirring for 10 min until completely dissolved.

[0082] (3) Transfer the mixed system to a reaction vessel such as a reaction kettle, and carry out hydrothermal reaction at 180°C for 6 h;

[0083] During the hydrothermal reaction, by regulating the pH value to 9.5 - 10.5, hydrogen bonds are formed between the hydroxyl groups (-OH) on the ZnO surface and the carboxyl groups at the ends of PEG, realizing preliminary physical adsorption and generating the PEG-ZnO precursor.

[0084] (4) Centrifuge and separate the reaction product containing the PEG-ZnO precursor, and then disperse it in anhydrous ethanol.

[0085] (5) Add the silane coupling agent KH550 (3-aminopropyltriethoxysilane), with a dosage of 0.8% of the ZnO mass, and reflux at 60°C for 2 h. PEG forms Si-O-Zn covalent bonds with the ZnO surface through amino groups, enhancing the coating stability.

[0086] 4. Preparation of the liquid medicine in the liquid medicine layer

[0087] (1) Add the PEG-ZnO nanoparticles to the borneol solution, and perform ultrasonic treatment at 40 kHz for 30 min. Utilize the emulsifying effect of Tween 80 and the solubility of propylene glycol to uniformly disperse the PEG-ZnO nanoparticles.

[0088] (2) Add the Salvia miltiorrhiza extract and glycerol to the above mixed system of PEG-ZnO nanoparticles and borneol (avoid direct contact with high ionic strength physiological saline); then add physiological saline and adjust the pH value to 7.0, avoiding premature adjustment of the pH to affect the stability of the nanoparticles.

[0089] 5. Preparation of Conductive Layer

[0090] (1) Mix the aqueous conductive carbon paste with the positive electrode material (MnO2) and the negative electrode material (Zn) evenly. The mass ratio of the aqueous conductive carbon paste, the positive electrode material, and the negative electrode material is (3 - 5):0.5:0.5 (specifically, 5:0.5:0.5 can be selected) to prepare conductive ink.

[0091] (2) Use a rheology modifier to adjust the viscosity of the conductive ink to 3000 - 4000 mPa·s (specifically, 3500 mPa·s can be selected); deposit the conductive ink on the surface of the substrate (specifically, non-woven fabric can be selected) by screen printing.

[0092] The deposition method can be to use a squeegee to scrape evenly at a 45° angle (pressure 0.2 - 0.4 MPa, speed 10 - 20 cm / s). Repeat printing 3 times to ensure uniform electrode thickness (deposition thickness 10 - 20 μm).

[0093] (3) Cure in an oven at 120°C for 30 min.

[0094] 6. Preparation of Microcurrent Eye Patch

[0095] (1) Mix the medicinal liquid (containing salvia extract, borneol, PEG-ZnO) with the PEG solution (10% w / v, molecular weight 3500 Da) at a volume ratio of 1:1, add 0.1% (w / v) Tween 80 as an emulsifier, and homogenize (8000 rpm, 5 min) to form a stable emulsion.

[0096] The emulsion is atomized into tiny droplets through a nozzle, and the solvent (water) evaporates quickly to form microcapsules with the medicinal liquid encapsulated in a poly(D,L-lactic acid-co-glycolic acid) matrix. Collect the microcapsule powder, dry it in vacuum at 40°C for 2 h to remove residual moisture, sieve (150 mesh) for grading, and place it on the conductive layer printed with positive and negative electrodes to form a medicinal liquid layer;

[0097] (2) Bond each layer of the first non-woven fabric layer, the skin-friendly adhesive layer, the breathable and waterproof cotton cloth layer, and the second non-woven fabric layer according to the Figure 1 and Figure 2 structure to obtain the finished microcurrent eye patch.

[0098] The coating material used for the microcapsules provided in this example is poly(D,L-lactic acid-co-glycolic acid), the particle size of the microcapsules is 100 - 150 mesh, the conductive layer is a non-woven fabric printed with electrodes, the voltage is 0.4 - 0.7 V, and the current is 0.35 - 0.71 mA.

[0099] Examples 2 and 3: Influence of PEG with Different Molecular Weights on the Performance of PEG-ZnO Nanoparticles

[0100] This test example aims to study the influence of PEG with different molecular weights on the performance of PEG-ZnO nanoparticles. The preparation method of the microcurrent eye patch provided in this example is basically the same as that in Example 1, except that PEG with molecular weights of 2000, 3500 (in Example 1), and 5000 Da are used respectively in this example. When preparing the liquid medicine for the liquid medicine layer, the PEG-ZnO nanoparticles are added to the borneol solution, and the ultrasonic treatment time at 40 kHz is adjusted to 45 min to ensure the uniform dispersion of PEG with different molecular weights.

[0101] Example 4: Influence of the gradient ethanol precipitation method on the extraction effect of Salvia miltiorrhiza extract

[0102] The preparation method of the microcurrent eye patch provided in this example is basically the same as that in Example 1, except for the gradient ethanol precipitation method, which is shown in Table 1 below.

[0103] Table 1

[0104]

[0105] According to the test method of the retention rate in the following test examples, the retention rates of the thermosensitive components salvianolic acid B, tanshinone IIA, and total polysaccharides are detected.

[0106] The test results are shown in Table 2 below. It can be seen that combining low temperature (45°C) with low-concentration ethanol gradient precipitation can significantly improve the retention rate of thermosensitive components.

[0107] Table 2

[0108]

[0109] Examples 5 - 8 and Comparative Example 1: Influence of the raw material dosage of different liquid medicine layers on the microcurrent eye patch

[0110] The preparation methods of the microcurrent eye patches provided in Examples 5 - 8 and Comparative Example 1 are basically the same as that in Example 1, except for the raw material dosage of each liquid medicine layer. Borneol is not added to the liquid medicine raw materials in Comparative Example 1. The details are shown in Table 3 below.

[0111] Table 3

[0112] Comparative Example 2

[0113] The preparation method of the microcurrent eye patch provided in this comparative example is basically the same as that in Example 1. The difference is that no electrodes are printed on the conductive layer in the microcurrent eye patch of this comparative example.

[0114] Comparative Example 3

[0115] The preparation method of the microcurrent eye patch provided in this comparative example is basically the same as that of Example 1. The difference is that in the microcurrent eye patch of this comparative example, the PEG-ZnO nanoparticles are replaced with conventional ZnO nanoparticles (0.03% w / v), that is, no PEG coating is carried out.

[0116] The preparation method of ZnO nanoparticles is as follows: Mix a Zn(NO3)2 solution (0.1 mol / L) and an NaOH solution (0.2 mol / L) at a volume ratio of 1:2 (the NaOH solution is in excess), and stir magnetically at 500 rpm for 30 min to form a white suspension; transfer it to a high-pressure reaction kettle, carry out a hydrothermal reaction at 180 °C for 6 h, centrifuge and wash after cooling, and dry to obtain ZnO.

[0117] Comparative Example 4

[0118] The preparation method of the microcurrent eye patch provided in this comparative example is basically the same as that of Example 1. The difference is that no PEG-ZnO nanoparticles or conventional ZnO nanoparticles are added to the microcurrent eye patch of this comparative example.

[0119] Comparative Example 5

[0120] The preparation method of the microcurrent eye patch provided in this comparative example is basically the same as that of Example 1. The difference is that when preparing the salvia miltiorrhiza extract in this comparative example, gradient ethanol precipitation is not used, but the salvia miltiorrhiza medicinal materials soaked in physiological saline are directly precipitated with 80% (v / v) ethanol at one time.

[0121] Test Example: Performance Test of Microcurrent Eye Patch

[0122] The performance test methods and results of the microcurrent eye patches prepared in the above Examples 1-8 and Comparative Examples 1-6 are shown as follows.

[0123] 1. Conductivity

[0124] Immerse the conductivity meter probe in a standard potassium chloride solution, and adjust it to the conductivity value corresponding to 25 °C (1.413 mS / cm) to complete the calibration. After keeping the mixed medicinal liquid in a water bath at 25 °C for 30 minutes, take 50 mL of the medicinal liquid and inject it into the sample cup, insert the probe (make sure it is completely immersed and there are no bubbles), and let it stand for 10 seconds to read the value. Each sample is measured 3 times repeatedly, and the average value is taken.

[0125] 2. Transdermal Efficiency

[0126] Use a Franz diffusion cell. Place porcine skin (porcine skin of 1-month-old Bama pigs, purchased from Guangquan Biotechnology (Shandong) Co., Ltd.) in the receiving chamber of the diffusion cell, with the side attached with the eye patch mixture facing the supply chamber, and take out the receiving liquid from the receiving chamber at 5, 10, 20, 30, and 40 min.

[0127] Determine the concentrations of the main active ingredients (total polysaccharides, salvianolic acid B, tanshinone) in the Danshen extract using HPLC. Plot the transdermal curves based on the cumulative drug permeation amount and time, and calculate the permeation efficiency of the main active ingredients in the Artemisia argyi liquid. The results of the permeation efficiency are shown in Table 1, where the permeation efficiency = the content of the main active ingredient in the receiving solution / the content of the main active ingredient in the Danshen extract.

[0128] 3. Sedimentation rate at 8 hours

[0129] Vertically fix the colorimetric tube containing the eye patch mixture in the incubator and let it stand for 48 hours; do not vibrate or tilt it during this period. Carefully pipette the upper layer liquid, dilute it to the original concentration; measure the absorbance using a spectrophotometer at a wavelength of 600 nm.

[0130] Formula for calculating the sedimentation rate:

[0131]

[0132] 4. ΔE reduction rate

[0133] Select 130 volunteers with dark eye circles, and then divide the volunteers into 13 groups, with 10 people in each group. Then, in each group, apply Examples 1 - 8 and Comparative Examples 1 - 5 to the eyes of different volunteers respectively. Apply twice a day for 60 days. Measure the color difference (ΔE) between the normal skin color before and after use using a colorimeter. The formula for calculating the color difference reduction rate is:

[0134]

[0135] 5. Retention rate

[0136] Use a Franz diffusion cell, place the skin model in the receiving chamber of the diffusion cell, with the side attached with the eye patch mixture facing the supply chamber. Take out the receiving solution from the receiving chamber at 5, 10, 20, 30, 40 min, and determine the concentrations of the main active ingredients (total polysaccharides, salvianolic acid B, tanshinone) in the Danshen extract and the receiving solution using HPLC, and calculate the above - mentioned main active ingredients in the Danshen extract and the receiving solution. The formula for calculating the retention rate of the main active ingredient is:

[0137]

[0138] The test results of the conductivity, transdermal efficiency, 48 - h sedimentation rate, ΔE reduction rate, and retention rate of the micro - current eye patches prepared in Examples 1 - 8 and Comparative Examples 1 - 6 are shown in Tables 4 and 5 below.

[0139] Table 4

[0140]

[0141] Table 5 Retention Rate of Active Ingredients

[0142]

[0143] Based on Table 4 above, from the test results of Examples 1-3 and Comparative Examples 3-4, it can be seen that PEG with a molecular weight of 3500 Da achieves the best balance in conductivity, stability, and transdermal efficiency.

[0144] From the test results of Examples 1, 5 and Comparative Example 5, it can be seen that low temperature (45°C) combined with low-concentration ethanol gradient precipitation can significantly improve the retention rate of thermosensitive components. If the gradient ethanol precipitation method is replaced with a one-time precipitation of 80% ethanol, there will be problems of greater loss of thermosensitive components and lower conductivity.

[0145] From the test results of Examples 1, 5-8 and Comparative Examples 1, 3, 4, it can be seen that changing the dosage of each raw material component will affect the conductivity of the eye patch extract. Especially when borneol is not added, or PEG-ZnO nanoparticles / ordinary ZnO nanoparticles are not added, or PEG-ZnO nanoparticles are replaced with conventional ZnO nanoparticles, it will not only affect the stability of the eye patch mixture, but also reduce the conductivity of the drug, thereby affecting the skin penetration efficiency of the drug. This also fully demonstrates that the synergistic application of salvia extract and PEG-ZnO nanoparticles has a very significant positive impact on the conductivity and transdermal efficiency of the liquid medicine layer.

[0146] The above specific embodiments have described the implementation of the present invention in detail. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the claims and technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple variations all belong to the protection scope of the present invention.

Claims

1. A micro-current eye patch for reducing dark circles, characterized in that: It comprises a conductive layer and a drug solution layer located above the conductive layer, wherein a positive electrode and a negative electrode are arranged on the conductive layer; the drug solution layer is composed of microcapsules filled with drug solution, wherein the raw materials of the drug solution include 76-84% of salvia miltiorrhiza extract, 0.072-0.089% of borneol, 1.98-2.18% of propylene glycol, 3.6-4.4% of glycerol, 0.75-0.94% of Tween, 0.0003-0.0015% of PEG-ZnO nanoparticles, and the rest is physiological saline according to mass percentage; The preparation method of the PEG-ZnO nanoparticles is: The zinc salt aqueous solution and excess alkali solution are mixed and stirred to obtain a white suspension, and PEG is added and stirred to dissolve; the mass ratio of PEG to ZnO is 1:(5-10); Hydrothermal reaction was carried out at 170-190°C for 5-10 h, during which the pH value of the reaction system was adjusted to 9.5-10.5 to obtain a PEG-ZnO precursor; The precipitate was collected by centrifugation and dispersed in anhydrous ethanol. A silane coupling agent in an amount of 0.5-1% by weight of ZnO was added, and the mixture was refluxed at 50-70° C. for 1.5-3 h to obtain the PEG-ZnO nanoparticles.

2. The microcurrent eye patch for reducing dark circles according to claim 1, characterized in that: In the preparation method of the PEG-ZnO nanoparticles, the hydrothermal reaction conditions are 180° C. for 6 hours.

3. The microcurrent eye patch for reducing dark circles according to claim 1, characterized in that: In the preparation method of the PEG-ZnO nanoparticles, the reflux condition after adding the silane coupling agent is reflux at 60° C. for 2 h.

4. The microcurrent eye patch for reducing dark circles according to claim 1, characterized in that: The raw materials of the medicinal solution include 84% of salvia miltiorrhiza extract, 0.075% of borneol, 1.98% of propylene glycol, 4% of glycerol, 0.8% of Tween, 0.0015% of PEG-ZnO nanoparticles, and the rest is normal saline according to mass percentage.

5. The microcurrent eye patch for reducing dark circles according to claim 1, characterized in that: The preparation method of the salvia miltiorrhiza extract is as follows: taking the medicinal material salvia miltiorrhiza and soaking it in physiological saline; adding ethanol solution to the mixed solution until the ethanol volume concentration in the system is 30-25%, and standing at 4°C for 10-14 hours to complete primary alcohol precipitation; Take the supernatant after the primary alcohol precipitation and add ethanol to the system until the ethanol volume concentration is 60-65%, and let it stand at 4°C for 8-10 hours to complete the secondary alcohol precipitation; Take the supernatant after the secondary alcohol precipitation and add ethanol until the ethanol volume concentration in the system is 80-85%, and let it stand at 4°C for 5-7 hours to complete the final alcohol precipitation; The supernatant after the final alcohol precipitation is taken and concentrated at low temperature under vacuum to a relative density of 1.15-1.20 at 25° C. to obtain the Danshen extract.

6. The microcurrent eye patch for reducing dark circles according to claim 1, characterized in that: A first non-woven fabric layer is also provided below the conductive layer.

7. The micro-current eye patch for reducing dark circles according to claim 6, characterized in that: A skin-friendly adhesive layer is arranged around the lower surface of the first non-woven fabric layer.

8. The micro-current eye patch for reducing dark circles according to claim 1, characterized in that: A breathable and waterproof cotton cloth layer is arranged above the liquid medicine layer.

9. The micro-current eye patch for reducing dark circles according to claim 8, characterized in that: A second non-woven fabric layer is arranged above the breathable and waterproof cotton fabric layer.

10. A method for preparing the microcurrent eye patch for reducing dark circles according to any one of claims 1 to 9, characterized in that: The following steps are involved: Add borneol to propylene glycol and stir to dissolve, then add Tween and mix evenly, then add the PEG-ZnO nanoparticles and mix evenly to obtain a mixed system; stir and mix the salvia miltiorrhiza extract, glycerol, the mixed system and physiological saline evenly, and adjust the pH value of the system to neutral to obtain a medicinal solution; The drug solution is encapsulated with microcapsule materials to form microcapsules, which are then placed on the conductive layer.

Images