Eye protection cream and eye pad composition for relieving asthenopia and preparation method of eye protection cream and eye pad composition

Abstract

The invention relates to the technical field of medical ophthalmology, in particular to eye protection cream for relieving asthenopia, an eye patch composition and a preparation method of the eye protection cream. The eye protection cream comprises 2.5-3.5 parts of morin-rosmarinic acid nano-micelle; 2.0 to 2.4 parts of a ginsenoside Rg3-rutin micro-capsule; the gel is included by 4.5 to 5.5 parts of capsaicin-cyclodextrin-hydroxypropyl methyl cellulose; 0.6 to 1.0 part of nano silicon dioxide aerogel-sodium hyaluronate moisturizing particles; 65.0 to 68.0 parts of an olive oil-shea butter-carnauba wax composite matrix; and 22.0 to 23.0 parts of gellan gum, xanthan gum and guar gum composite hydrogel. According to the invention, a novel nano-carrier is adopted, so that the stability and bioavailability of active ingredients are greatly improved. Therefore, the effects of resisting inflammation, resisting oxidation, promoting blood circulation of eyes and the like are more effectively exerted, and the asthenopia symptom can be more remarkably relieved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical ophthalmology, and in particular to an eye ointment and an eye patch composition for relieving visual fatigue and a preparation method thereof. Background Art

[0002] In today's digital age, with the widespread use of electronic devices, visual fatigue has become a common eye health problem. After prolonged use of computers, mobile phones, and other devices, people often experience symptoms such as dry eyes, soreness, and blurred vision. This not only affects work and study efficiency but can also cause long-term damage to eye health. To alleviate visual fatigue, a variety of eye protection products have emerged on the market, including common eye ointments and eye patches. Most of these products utilize the nutritional components and pharmacological effects of natural plant extracts to relieve eye fatigue and protect vision. However, existing eye protection products still have many shortcomings in terms of composition and preparation processes, making it difficult to meet people's demand for efficient, safe, and comfortable eye protection products.

[0003] In the prior art, the formula ingredients of eye ointments and eye patches are relatively simple, usually containing only a small amount of active ingredients, which are difficult to effectively relieve visual fatigue. At the same time, some eye protection products use a large amount of chemical additives, which may have adverse effects on the human body with long-term use and pose safety risks. In addition, the preparation process used in some products is relatively simple and fails to fully consider the stability and bioavailability of the active ingredients, making the active ingredients easily inactivated during storage or use, and unable to fully exert their effects. Therefore, we propose eye ointment and eye patch compositions for relieving visual fatigue and their preparation methods. Summary of the Invention

[0004] In view of the deficiencies in the prior art, the present invention provides an eye ointment, an eye patch composition and a preparation method thereof for relieving visual fatigue, thereby solving the technical problems mentioned in the background technology.

[0005] To achieve the above objectives, the present invention is implemented through the following technical solutions:

[0006] An eye ointment for relieving visual fatigue comprises the following components in parts by weight:

[0007] Morin-rosmarinic acid nanomicelles: 2.5-3.5 parts;

[0008] Ginsenoside Rg3-rutin microcapsules: 2.0-2.4 parts;

[0009] Capsaicin-cyclodextrin-hydroxypropyl methylcellulose inclusion gel: 4.5-5.5 parts;

[0010] Nano-silica aerogel-sodium hyaluronate moisturizing particles: 0.6-1.0 parts;

[0011] Olive oil-shea butter-carnauba wax composite matrix: 65.0-68.0 parts;

[0012] Gellan gum-xanthan gum-guar gum composite hydrogel: 22.0-23.0 parts.

[0013] In one possible implementation, the morin-rosmarinic acid nanomicelles are prepared by a self-assembly method using 6.0 parts of 20% poloxamer 407 and 2.4 parts of 8% cholesterol as carrier materials, with an average particle size of 55±3 nm and an encapsulation efficiency of not less than 93%.

[0014] In one possible implementation, the ginsenoside Rg3-rutin microcapsules are prepared using sodium alginate and chitosan as wall materials by an emulsification-crosslinking method, with an average particle size of 200±10 nm and an encapsulation efficiency ≥91%; the sodium alginate accounts for 1.8% of the total mass of the microcapsules, and the chitosan accounts for 1.5% of the total mass of the microcapsules.

[0015] In one possible implementation, the capsaicin-cyclodextrin-hydroxypropyl methylcellulose inclusion gel is prepared by freeze-drying capsaicin and cyclodextrin in a molar ratio of 1:1.2, and then adding hydroxypropyl methylcellulose solution and treating at 45°C and an ultrasonic power of 250W for 15 minutes to form the inclusion gel.

[0016] In one possible implementation, the nano-silica aerogel-sodium hyaluronate moisturizing particles are prepared by mixing nano-silica aerogel prepared by a sol-gel method using ethyl orthosilicate as a precursor with sodium hyaluronate in a mass ratio of 3:1, and dispersing the mixture at a stirring speed of 700 rpm and a temperature of 40°C for 20 minutes.

[0017] In one possible implementation, the olive oil-shea butter-carnauba wax composite matrix is ​​prepared by mixing 52.0 parts of olive oil, 33.0 parts of shea butter, and 15.0 parts of carnauba wax in a mass ratio, and melting and stirring them uniformly in a 75°C water bath at a stirring speed of 300 rpm.

[0018] In a possible implementation, the gellan gum-xanthan gum-guar gum composite hydrogel is formed by mixing 38.0 parts of gellan gum, 32.0 parts of xanthan gum, and 30.0 parts of guar gum according to a mass ratio, adding deionized water, heating to 80° C. to fully dissolve, and cooling.

[0019] In one possible implementation, a method for preparing an eye ointment for relieving visual fatigue comprises the following steps:

[0020] S1: Preparation of active ingredient carriers, including morin-rosmarinic acid nanomicelles and ginsenoside Rg3-rutin microcapsules;

[0021] S2: Preparation of functional excipients, including capsaicin-cyclodextrin-hydroxypropyl methylcellulose inclusion gel and nano-silica aerogel-sodium hyaluronate moisturizing microparticles;

[0022] S3: melting and mixing the matrices to prepare an olive oil-shea butter-carnauba wax composite matrix and a gellan gum-xanthan gum-guar gum composite hydrogel, respectively, and mixing the two to form a composite matrix;

[0023] S4: Composite optimization: the active ingredient carrier prepared in S1 and the functional excipient prepared in S2 were sequentially added to the composite matrix prepared in S3, and mixed at 40°C and 300 rpm for 1.5 hours to ensure uniform dispersion of the ingredients;

[0024] S5: Product molding and quality inspection: fill the evenly mixed eye ointment into aluminum-plastic soft tubes, each with a capacity of 15g, and conduct particle size and potential detection, rheological property testing, in vitro release determination and stability investigation.

[0025] In one possible implementation, an eye patch composition of an eye ointment for relieving visual fatigue comprises an eye ointment accounting for 25% of the total mass of the eye patch, a base material being a non-woven fabric, and a packaging material being an aluminum foil composite film.

[0026] Beneficial effects compared with existing technologies:

[0027] 1. In this scheme, new nano-carriers such as morin-rosmarinic acid nano-micelles and ginsenoside Rg3-rutin microcapsules are used to greatly improve the stability and bioavailability of the active ingredients. The addition of nano-micelles and microcapsules enables the active ingredients to be efficiently absorbed by the eyes, thereby more effectively exerting anti-inflammatory, antioxidant, and eye blood circulation promoting effects, and can more significantly relieve the symptoms of visual fatigue. Similarly, ginsenoside Rg3 and rutin are extracted from ginseng and Sophora japonica seeds, respectively, and have the effects of promoting eye blood circulation, enhancing eye cell vitality, and maintaining eye blood vessel elasticity. The emulsification-cross-linking method is used to prepare microcapsules and encapsulate these two ingredients, which can effectively protect their activity, prolong the action time, and enable the product to continuously release active ingredients during use, providing a lasting fatigue-relieving effect for the eyes;

[0028] 2. In this solution, capsaicin-cyclodextrin-hydroxypropyl methylcellulose inclusion gel and nano-silica aerogel-sodium hyaluronate moisturizing particles are introduced. When the capsaicin inclusion gel comes into contact with the skin around the eyes and the temperature rises, it can slowly release capsaicin, producing a gentle warming sensation and promoting blood circulation in the eyes. At the same time, the nano-silica aerogel-sodium hyaluronate moisturizing particles physically absorb water to form a three-dimensional moisturizing network, delaying water evaporation, forming a moisturizing film on the surface of the eye skin, and enhancing the permeability of active ingredients. The synergistic effect of this functional excipient achieves the dual effects of moisturizing and promoting blood circulation, bringing users a more comfortable and effective use experience;

[0029] 3. In this solution, the combination of an olive oil-shea butter-carnauba wax composite matrix and a gellan gum-xanthan gum-guar gum composite hydrogel provides excellent spreadability and skin compatibility, making the product easy to use and non-irritating to the eyes. Furthermore, during the quality inspection process, products are comprehensively evaluated through multiple testing methods. Only products that meet all requirements are released for sale, providing users with high-quality eye protection products and resolving the quality and stability issues of existing eye protection products. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention and implement it according to the contents of the specification, the following is a detailed description of the preferred embodiments of the present invention with reference to the accompanying drawings.

[0031] Figure 1 Schematic diagram of the process for preparing the eye ointment of the present invention;

[0032] Figure 2 The figure is a schematic flow chart of the preparation method of the eye patch composition of the present invention. DETAILED DESCRIPTION

[0033] Preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the present invention can be implemented in various forms, and therefore the present invention is not limited to the embodiments described below. In addition, in order to more clearly describe the present invention, components that are not related to the present invention will be omitted from the drawings.

[0034] The technical solutions in the embodiments of the present application are to solve the problems of the above-mentioned background technology, which are generally as follows:

[0035] Example 1:

[0036] This example describes an eye ointment for relieving visual fatigue and its preparation method. This ointment utilizes a carefully selected variety of materials, with the active ingredients extracted from natural plants and other raw materials. These ingredients are processed for more efficient absorption by the eye. Functional excipients are combined and processed to enhance the stability of the active ingredients and impart unique properties to the product. The matrix material is formulated to provide excellent spreadability and skin compatibility. These materials work synergistically to alleviate visual fatigue and protect eye health.

[0037] 1. Material composition

[0038] 1. Active ingredient

[0039] Morin-rosmarinic acid nano-micelles: 2.5-3.5 parts by mass of the total. Morin is extracted from the white mulberry bark, and the purity can reach 95% by water extraction and alcohol precipitation combined with silica gel column chromatography. It has anti-inflammatory and antioxidant effects and can relieve eye inflammation. Rosmarinic acid is extracted from rosemary, extracted by ethanol reflux and then purified by macroporous adsorption resin, with a purity of 96%. It can effectively scavenge free radicals and protect eye tissues. 20% poloxamer 407 (that is, the proportion of poloxamer 407 in the total mass of the preparation system is 20%) and 8% cholesterol (the proportion of cholesterol in the total mass of the preparation system is 8%) are used as carrier materials.

[0040] Nanomicelles were prepared using a self-assembly method. This method involves dissolving a drug and a carrier material in a suitable mixed solvent under certain conditions. By modifying the environmental conditions (such as adding another solvent), the drug and carrier material spontaneously aggregate and assemble at the molecular level to form nanomicelles. Specifically, morin, rosmarinic acid, and the carrier material were dissolved in an acetone-water mixture (3:7 by volume). Deionized water was slowly added dropwise at 35°C and a stirring speed of 600 rpm for dialysis. The purpose of adding deionized water is to change the solvent properties in the system, promoting the formation of nanomicelles. The dialysis process also removes acetone, ultimately yielding nanomicelles with an average particle size of 55±3 nm and an encapsulation efficiency of no less than 93%.

[0041] Ginsenoside Rg3-rutin microcapsules: 2.0-2.4 parts by weight. Ginsenoside Rg3 is extracted from ginseng, separated by supercritical CO2 extraction and high-speed countercurrent chromatography, to a purity of 98%. It promotes blood circulation in the eyes and enhances ocular cell viability. Rutin is extracted from Sophora japonica seeds using an alkaline extraction and acid precipitation method, which involves dissolving the rutin under alkaline conditions and then precipitating it through acidification. After the initial extraction, recrystallization is required to further improve the purity, ultimately reaching 97%, helping to maintain ocular vascular elasticity. Sodium alginate (1.8% of the total microcapsule weight) and chitosan (1.5% of the total microcapsule weight) are used as the wall materials.

[0042] Microcapsules are prepared using an emulsification-crosslinking method. This method involves first emulsifying the drug and wall material to form an oil-in-water or water-in-oil emulsion system. The wall material is then cross-linked using a crosslinking agent to form robust microcapsules. Specifically, ginsenoside Rg3 and rutin are mixed with the wall material and added dropwise to an oil phase formed by liquid paraffin and Span-80 at a stirring speed of 700 rpm for emulsification. A 1.0% by mass calcium chloride solution is then added for cross-linking for 20 minutes. Finally, the mixture is filtered, washed, and dried to yield microcapsules with an average particle size of 200±10 nm and an encapsulation efficiency of ≥91%.

[0043] 2. Functional excipients

[0044] Capsaicin-β-cyclodextrin-hydroxypropyl methylcellulose inclusion gel: 4.5-5.5 parts by weight. Capsaicin and β-cyclodextrin are first mixed in a molar ratio of 1:1.2 and freeze-dried to prepare the inclusion complex. The specific procedure is as follows: β-cyclodextrin is prepared into an 18% (w / v) aqueous solution, i.e., 18g of β-cyclodextrin per 100ml of solution. After adding capsaicin, the mixture is stirred for inclusion for 10 hours, and then freeze-dried to obtain the inclusion complex. Hydroxypropyl methylcellulose is a commonly used gel matrix material. It is prepared into a 4% (w / v) aqueous solution, i.e., 4g of hydroxypropyl methylcellulose per 100ml of solution. The inclusion complex is added to the hydroxypropyl methylcellulose solution and treated at 45°C and an ultrasonic power of 250W for 15 minutes to form an inclusion gel. The gel forms a gel network with hydroxypropyl methylcellulose through hydrogen bonds; when the temperature of the skin in contact with the eyes rises to above 32°C, the gel network relaxes and capsaicin is slowly released, producing a mild warming sensation, promoting blood circulation in the eyes, and the gel form can keep the ingredients in the eyes for a longer time.

[0045] Nano-silica aerogel-sodium hyaluronate moisturizing particles: 0.6-1.0 parts by weight. Nano-silica aerogel is prepared by the sol-gel method. The specific operation is: using tetraethyl orthosilicate as a precursor, hydrolysis and condensation reaction is carried out in an ethanol-water system, and the reaction is promoted by acid or base catalysis. After aging and solvent replacement, it is dried by supercritical carbon dioxide to obtain an average pore size of 25nm and a specific surface area of ​​750m 2 / g of aerogel. Sodium hyaluronate, with a molecular weight of 1.8 million Da, was mixed with aerogel in a mass ratio of 3:1 and dispersed at 700 rpm and 40°C for 20 minutes to form moisturizing microparticles. These microparticles physically absorb water, forming a three-dimensional moisturizing network with the sodium hyaluronate, which slows evaporation and exhibits excellent moisturizing properties. They form a moisturizing film on the surface of the eye skin and facilitate the penetration of active ingredients.

[0046] 3. Matrix material

[0047] Olive oil-shea butter-carnauba wax composite matrix: 65.0-68.0 parts by weight. Olive oil, rich in unsaturated fatty acids, accounts for 52% and offers excellent moisturizing and skin permeability; shea butter, 33%, is rich in vitamins and fatty acids, nourishing the eye area; and carnauba wax, 15%, adjusts the matrix's hardness and formability. Olive oil, shea butter, and carnauba wax are mixed in a mass ratio of 52%, 33%, and 15%. Specifically, for a total mass of 100 units, olive oil accounts for 52 units, shea butter for 33 units, and carnauba wax for 15 units. Melt in a 75°C water bath and stir thoroughly.

[0048] Gellan gum-xanthan gum-guar gum composite hydrogel: 22.0-23.0 parts by weight. Gellan gum accounts for 38%, xanthan gum 32%, and guar gum 30%. The three gums are mixed according to their mass ratio, added to deionized water, heated to 80°C to fully dissolve, and cooled to form a hydrogel. This hydrogel has strong water retention and good adhesion, allowing the eye cream to adhere tightly to the skin around the eyes, making it easy to apply and use.

[0049] 2. Main instruments and equipment

[0050] Multifunctional Ultrasonic Extractor: Used for extracting active ingredients such as morin, rosmarinic acid, ginsenoside Rg3, and rutin. This device features ultrasonic power adjustment, temperature control, and time setting. During the extraction process, the extraction yield of active ingredients can be improved by setting the appropriate ultrasonic power (e.g., 300W), temperature (50°C), and time (30 minutes).

[0051] Vacuum Freeze Dryer: Used for preparing capsaicin-β-cyclodextrin inclusion complexes and other materials requiring drying. The cold trap temperature can reach -55°C, with a vacuum level of ≤10Pa. Under low-temperature vacuum, moisture in the material sublimates directly, effectively protecting heat-sensitive ingredients such as capsaicin from volatilization or decomposition due to high temperatures during the drying process, ensuring the quality and activity of the inclusion complex.

[0052] High-pressure homogenizer: Used for preparing nanomicelles and processing matrix mixing. With a maximum operating pressure of 200 MPa, the material is subjected to intense shearing, impaction, and cavitation effects as it passes through narrow gaps under high pressure, resulting in particle refinement. When preparing morin-rosmarinic acid nanomicelles, the pressure (e.g., 150 MPa) and the number of cycles (two) can be adjusted to precisely control the nanomicelle size to the desired 55 ± 3 nm, ensuring consistent product quality.

[0053] Rotary Evaporator: Used to remove solvents during the preparation of nanomicelles and microcapsules. Equipped with rotation, heating, and pressure reduction functions, it allows solutions to form thin films in the rotating flask, accelerating solvent evaporation. The temperature can be controlled from room temperature to 100°C, and the rotation speed is adjustable. In the preparation of ginsenoside Rg3-rutin microcapsules, it is used to remove organic solvents used in the emulsification process. It is easy to operate and effectively concentrates solutions.

[0054] Laser Particle Size Analyzer: Real-time measurement of the particle size distribution and zeta potential of nanomicelles, microcapsules, nanosilica aerogel-sodium hyaluronate moisturizing microparticles, and other particles. With a measurement range of 0.01nm-3000μm, it can accurately determine the average particle size, polydispersity index, and zeta potential. During the production process, product quality can be monitored at all times to ensure that particle size meets requirements (e.g., nanomicelle average particle size D50 ≤ 55nm, polydispersity index (PDI) ≤ 0.15, and absolute zeta potential ≥ 20mV). If test results fall short of standards, process parameters can be adjusted promptly.

[0055] Scanning electron microscopy (SEM): Used to observe the surface morphology and particle size distribution of materials such as nanomicelles, microcapsules, and nanosilica aerogels. Operating at an accelerating voltage of 0.5-30 kV, SEM offers high resolution, clearly demonstrating the material's microstructure. By observing the material's morphology, size, and surface characteristics, it is possible to assess whether the preparation results meet expectations, providing intuitive evidence for process optimization.

[0056] Rheometer: Measure the rheological properties of eye ointment bases and finished products, such as storage modulus (G′), loss modulus (G″), and viscosity. Equipped with different types of fixtures, it can perform temperature, frequency, and strain sweeps. When optimizing the base formulation and preparation process, measuring rheological properties can be used to adjust the proportion and mixing conditions of the base materials to ensure good spreadability and stability of the eye ointment. For example, the storage modulus (G′) of the composite base is required to be 300-500 Pa and the loss modulus (G″) is required to be 100-200 Pa at 25°C.

[0057] High-Performance Liquid Chromatography (HPLC): Used to determine the content and in vitro release of active ingredients. Equipped with a UV-Vis detector or other suitable detector, it can detect components based on their absorption wavelengths. By setting appropriate chromatographic conditions, such as mobile phase composition, flow rate, and column temperature, it can accurately measure the content and release of ingredients such as morin, rosmarinic acid, ginsenoside Rg3, and rutin, with high sensitivity and accurate results.

[0058] 3. Preparation method of eye ointment

[0059] S1: Preparation of active ingredient carrier

[0060] Preparation of Morin-Rosmarinic Acid Nanomicelles: 3.0 parts of Morin, 3.0 parts of Rosmarinic Acid, 6.0 parts of 20% Poloxamer 407, and 2.4 parts of 8% Cholesterol were dissolved in an acetone-water mixture (volume ratio 3:7) to prepare a 12% (w / v) solution. This solution was slowly added dropwise to deionized water at 35°C and a stirring speed of 600 rpm for 12 hours. The dialysis bag had a molecular weight cutoff of 3500 Da and the dialysis time was 12 hours. After removing the acetone, the nanomicelle solution was obtained. The solution was transferred to a high-pressure homogenizer and homogenized twice at 150 MPa to produce Morin-Rosmarinic Acid Nanomicelles. Laser particle size analysis was used to determine the average particle size (D50) to be ≤55 nm, the polydispersity index (PDI) to be ≤0.15, and the absolute value of the zeta potential to be ≥20 mV. If the particle size D50 is greater than 55 nm or the PDI is greater than 0.15, increase the homogenization pressure to 180 MPa or the number of cycles to 3 times; if the absolute value of the Zeta potential is less than 20 mV, add an appropriate amount of sodium dodecylbenzenesulfonate to adjust the potential and retest until it meets the standard.

[0061] Preparation of ginsenoside Rg3-rutin microcapsules: 2.2 parts ginsenoside Rg3 and 2.2 parts rutin were mixed with sodium alginate (1.8% of the total microcapsule mass) and chitosan (1.5% of the total microcapsule mass). An appropriate amount of deionized water was added to prepare an aqueous solution with a concentration of 10% (w / v). With stirring at 700 rpm, the aqueous solution was added dropwise to a liquid paraffin oil phase containing Span-80 (3% of the liquid paraffin mass). The mixture was emulsified for 15 minutes to form a stable oil-in-water emulsion. A 1.0% calcium chloride solution was then added to the emulsion for cross-linking for 20 minutes. The microcapsules were then collected by filtration, washed three times with petroleum ether to remove the liquid paraffin, and finally dried under vacuum at 40°C for 12 hours to obtain ginsenoside Rg3-rutin microcapsules. Use a laser particle size analyzer to test for an average particle size D50 ≤ 200 nm, a polydispersity index (PDI) ≤ 0.18, and an absolute zeta potential ≥ 18 mV. If the particle size or PDI does not meet the requirements, adjust the emulsification speed, crosslinking time, or wall material ratio. If the zeta potential does not meet the requirements, add an appropriate amount of polyethylene glycol to adjust the potential, re-prepare, and re-test.

[0062] S2: Preparation of functional excipients

[0063] Preparation of capsaicin-β-cyclodextrin-hydroxypropyl methylcellulose inclusion gel: Prepare 0.6 parts of β-cyclodextrin into an 18% (w / v) aqueous solution, heat to 60°C, add 0.5 parts of capsaicin at a molar ratio of 1:1.2, and stir for 10 hours. Freeze the inclusion solution to -40°C for 2 hours, then dry in a vacuum freeze dryer at a vacuum of ≤10 Pa for 24 hours to obtain the capsaicin-β-cyclodextrin inclusion complex. Prepare 0.8 parts of hydroxypropyl methylcellulose into a 4% (w / v) aqueous solution, heat to 50°C, and dissolve completely. Add the inclusion complex to the hydroxypropyl methylcellulose solution and treat at 45°C at an ultrasonic power of 250 W for 15 minutes to form 5.0 parts of the inclusion gel. The release temperature of capsaicin in the inclusion gel was detected by differential scanning calorimetry, and a clear release endothermic peak was required to begin at 32°C. If the requirement was not met, the ultrasonic treatment time or the concentration of hydroxypropyl methylcellulose was adjusted and the gel was re-prepared.

[0064] Preparation of Nano-Silica Aerogel-Sodium Hyaluronate Moisturizing Microparticles: Using tetraethyl orthosilicate as a precursor, nano-silica gel was prepared according to the sol-gel method. 0.4 parts of tetraethyl orthosilicate, 1.6 parts of ethanol, and 0.8 parts of water were mixed in a ratio of 1:4:2. A small amount of hydrochloric acid was added to adjust the pH to 2-3. The mixture was reacted at 60°C and a stirring speed of 500 rpm for 4 hours to form a sol. The sol was aged at room temperature for 24 hours, the solvent was replaced with ethanol three times, and then transferred to a high-pressure reactor and dried under supercritical carbon dioxide conditions (pressure 15 MPa, temperature 35°C) to obtain 0.8 parts of nano-silica aerogel.

[0065] Mix 0.7 parts of sodium hyaluronate (molecular weight 1.8 million Da) with 0.2 parts of nano-silica gel, add 10 ml of deionized water, and disperse at 700 rpm and 40°C for 20 minutes to form 1.0 parts of moisturizing microparticles. Observe the dispersion of the moisturizing microparticles using a scanning electron microscope. The aerogel should be evenly dispersed in the sodium hyaluronate aqueous solution without obvious agglomeration. Measure the particle size using a laser particle size analyzer. The average particle size D50 should be 100-300 nm, and the polydispersity index (PDI) should be ≤ 0.3. If these do not meet the requirements, adjust the dispersion conditions or the raw material ratio and re-prepare.

[0066] S3: Matrix melting and mixing

[0067] Preparation of olive oil-shea butter-carnauba wax composite matrix: 52.0 parts of olive oil, 33.0 parts of shea butter, and 15.0 parts of carnauba wax were weighed according to the mass ratio, placed in a stainless steel container, heated to 75°C in a water bath, and stirred at 300 rpm to completely melt and mix evenly.

[0068] Preparation of gellan gum-xanthan gum-guar gum composite hydrogel: Weigh 38.0 parts of gellan gum, 32.0 parts of xanthan gum, 30.0 parts of guar gum, add 100.0 parts of deionized water, stir evenly and heat to 80°C, continue stirring until completely dissolved. Wait for the solution to cool to room temperature to form a hydrogel. Slowly add the hydrogel to the molten olive oil-shea butter-carnauba wax composite matrix, use a high-speed shear emulsifier (speed 11000rpm) to emulsify for 20 minutes, so that the two matrices are fully mixed to form a uniform and stable composite matrix. Use a rheometer to measure the rheological properties of the composite matrix at 25°C, requiring the storage modulus (G′) to be 300-500Pa and the loss modulus (G″) to be 100-200Pa. If it does not meet the requirements, adjust the ratio of the two matrices or the emulsification time and re-measure until it meets the standards.

[0069] S4: Composite Optimization

[0070] 3.0 parts of morin-rosmarinic acid nanomicelles and 2.2 parts of ginsenoside Rg3-rutin microcapsules prepared in S1, 5.0 parts of capsaicin-β-cyclodextrin-hydroxypropyl methylcellulose inclusion gel prepared in S2, and 1.0 part of nanosilica aerogel-sodium hyaluronate moisturizing microparticles prepared in S3 were added in sequence, and mixed at 40°C and 300 rpm for 1.5 hours to uniformly disperse the ingredients.

[0071] The mixed system was subjected to a temperature scan using a rheometer (25-40°C, heating rate 1°C / min, frequency 1 Hz, strain 0.5%) to monitor changes in the storage modulus (G′) and loss modulus (G″). It was required that at 33-35°C, G′ and G″ change smoothly and G′>G″, indicating that the system has good rheological stability.

[0072] If the rheological properties do not meet the requirements, adjustments can be made based on the following principles:

[0073] If the storage modulus (G') is too low, i.e., G' < 300 Pa, it indicates that the elastic component of the system is insufficient, possibly due to insufficient support from the matrix. The proportion of olive oil in the composite matrix can be appropriately increased by 1%-3% (adjusted by 1% each time), while the proportion of shea butter can be reduced by 1%-3%, and the rheological properties can be re-measured. At the same time, it is also possible to consider appropriately increasing the proportion of gellan gum in the composite hydrogel. Gellan gum has good elasticity and can improve the storage modulus of the system.

[0074] If the loss modulus (G") is too high, that is, G">200Pa, it means that the viscosity of the system is too high. It may be that the addition of functional excipients or active ingredients has increased the intermolecular friction within the system. The addition amount of thermosensitive capsaicin-β-cyclodextrin-hydroxypropyl methylcellulose inclusion gel can be appropriately reduced. Because hydroxypropyl methylcellulose is a highly viscous polymer, reducing its dosage may reduce the viscosity of the system.

[0075] At the same time, changing the mixing temperature and time will also affect the rheological properties:

[0076] Properly increasing the mixing temperature can increase the speed of molecular movement, making the components more evenly dispersed in the matrix, and helping to improve the rheological stability of the system. However, if the mixing temperature is too high, it may cause the activity of certain heat-sensitive components (such as morin and rosmarinic acid) to decrease or even denature, so it needs to be controlled within a reasonable range.

[0077] Prolonging the mixing time can further promote the uniformity of the ingredients, ensuring sufficient interaction between the active ingredients, functional excipients, and matrix, and forming a more stable system. However, excessive mixing time may cause localized excessive shearing of the ingredients, which in turn may damage their structure, so it is necessary to adjust the mixing time according to the actual situation.

[0078] At the same time, a laser particle size analyzer is used to measure the particle size and zeta potential of each particle in the mixed system to ensure its stability and dispersibility. If the particle size is too large or the absolute value of the zeta potential is too low, it indicates uneven particle dispersion or aggregation, which will affect the stability and performance of the system. In this case, appropriate adjustments can be made to the nanomicelle and microcapsule preparation process parameters, such as increasing the homogenization pressure or the number of cycles when preparing nanomicelles, or adjusting the emulsification speed and cross-linking time when preparing microcapsules, to improve the particle dispersibility.

[0079] S5: Product molding and quality inspection

[0080] Fill the mixed eye ointment into aluminum-plastic tubes through a filling machine, with each tube containing 15g. Perform the following tests immediately after filling:

[0081] Particle Size and Zeta Potential Testing: Disperse a small amount of eye ointment sample in an appropriate amount of deionized water. Use a laser particle size analyzer to measure the particle size and zeta potential of the morin-rosmarinic acid nanomicelles, ginsenoside Rg3-rutin microcapsules, and nanosilica aerogel-sodium hyaluronate moisturizing microparticles. The average particle size of the nanomicelles must be 55±3nm, the average particle size of the microcapsules must be 200±10nm, the moisturizing microparticle size must be within the specified range, and the absolute zeta potential of each particle must be ≥18mV. If this does not meet the requirements, analyze the cause, return to the corresponding steps for adjustments, and re-prepare and re-test.

[0082] Rheological properties test: Use a rheometer to measure the rheological properties of the eye ointment at 25°C, 33°C, and 37°C, including parameters such as storage modulus (G′), loss modulus (G″), and viscosity. It is required that at 25°C, G′ is 300-500Pa and G″ is 100-200Pa; at 33-35°C, G′>G″ and the change is stable, meeting the product usage requirements. If the rheological properties are abnormal, return to step S4 and test again until it is qualified.

[0083] In vitro release rate determination: A transdermal diffusion instrument was used to conduct the experiment using a Franz diffusion cell. The receiving solution was a phosphate buffer solution with a pH of 7.4, a temperature of 37°C, and a stirring speed of 50 rpm. 5 mL of samples were taken at 1 h, 2 h, 4 h, 8 h, and 12 h (while supplemented with an equal amount of fresh receiving solution). The contents of morin, rosmarinic acid, ginsenoside Rg3, and rutin were determined using a high-performance liquid chromatograph, and the cumulative release rate was calculated. The release rate was required to be ≤28% for 2 h, ≥75% for 8 h, and ≤90% for 12 h. If the release rate did not meet the requirements, return to step S1 to adjust the carrier preparation or step S4 to optimize the composite process, and repeat the experiment and test.

[0084] Stability Assessment: Expose the eye ointment to 4°C, 25°C, and 40°C for three months. Observe monthly for changes in appearance, color, and viscosity, and test the active ingredient content. The ointment must be free of delamination, discoloration, or caking, with a viscosity change rate of ≤12% and an active ingredient content decrease rate of ≤10%. If stability does not meet the requirements, analyze the cause and return to the appropriate step to optimize the preparation process or adjust the formula, then repeat the stability test.

[0085] Example 2:

[0086] Based on the eye ointment for relieving visual fatigue and the preparation method thereof in Example 1, in order to further apply the eye ointment, this example introduces an eye patch composition prepared based on the eye ointment for relieving visual fatigue in Example 1 and the preparation method thereof.

[0087] 1. Composition of the eye patch composition

[0088] Eye ointment: The eye ointment prepared in Example 1 was used, accounting for 25% (w / w) of the total mass of the eye patch. The eye ointment contains morin-rosmarinic acid nanomicelles, ginsenoside Rg3-rutin microcapsules, capsaicin-β-cyclodextrin-hydroxypropyl methylcellulose inclusion gel, and nano-silica aerogel-sodium hyaluronate moisturizing microparticles. The specific composition and preparation method are detailed in Example 1.

[0089] Base material: Non-woven fabric is selected as the base material of the eye patch, which has good air permeability and fit. It can support the eye ointment and ensure its even distribution, and is cut into an eye mask shape suitable for wearing on the face.

[0090] Packaging material: Aluminum foil composite film is used for packaging, which has good barrier and protective properties and can maintain the stability and hygiene of the eye patch.

[0091] 2. Preparation method of eye patch composition

[0092] 1. Preparation of Eye Ointment

[0093] The eye ointment was prepared according to the method of Example 1, including the preparation of active ingredient nanocarriers (morin-rosmarinic acid nanomicelles, ginsenoside Rg3-rutin microcapsules), compounding of functional excipients (capsaicin-β-cyclodextrin inclusion gel, etc.), matrix melt mixing and system optimization, and finally filling into a 15 g soft tube packaged product.

[0094] When using eye ointment, it needs to be softened in a 30°C water bath for 10 minutes in advance to ensure fluidity.

[0095] 2. No gauze substrate treatment

[0096] The medical non-woven fabric is cut into an oval shape with a length of 30 mm and a width of 20 mm, which fits the size of the human face and eyes and is ergonomic.

[0097] The cut non-woven fabric was soaked in 0.5% ethanol solution for 10 minutes to remove surface impurities, then rinsed with deionized water three times and dried in an oven at 60°C for 2 hours.

[0098] The surface of the dried nonwoven fabric was sprayed with a 1% polyvinyl pyrrolidone (PVP) aqueous solution at a spraying rate of 0.5 mg / cm 2 , improve the adhesion with eye ointment, dry at room temperature and set aside.

[0099] 3. Applying and drying eye ointment

[0100] Use a slit coater to evenly apply the eye ointment to the central area of ​​the non-woven fabric. The coating thickness is controlled to 0.8 mm (achieved by adjusting the coating gap) and the coating speed is 50 mm / s to ensure that the coating is uniform and free of bubbles.

[0101] The coated nonwoven is placed in a drying oven at 25°C and 50% relative humidity for 2 hours to evaporate the solvent (e.g., ethanol) in the eye ointment, forming a semi-solid gel layer. After drying, the coating shrinks to a thickness of 0.5 mm. If the coating thickness deviation exceeds 10%, the slit gap of the coating machine needs to be calibrated.

[0102] 4. Slice forming and fixing

[0103] The dried nonwoven fabric is punched and sliced ​​through an elliptical forming die (long axis 30 mm, short axis 20 mm) with a slicing pressure of 8 MPa to ensure that the edges are neat and burr-free.

[0104] The sliced ​​eye patch was hot-pressed at 70°C and 1 MPa pressure for 10 minutes to allow the eye ointment to bond with the non-woven fabric fibers through hydrogen bonds, thereby improving the adhesion stability. The thickness of the eye patch after hot-pressing was 1.0 mm ± 0.1 mm.

[0105] 5. Packaging and sterilization

[0106] A single eye patch is placed in a pre-sterilized aluminum foil composite film bag and sealed with a heat sealer at a temperature of 180°C and a sealing edge width of 5mm to ensure airtightness.

[0107] The packaged eye patch is placed in a sterilization cabinet, and ethylene oxide gas (concentration 500 mg / L) is introduced. Sterilize at 37°C and 60% relative humidity for 60 minutes. After sterilization, ventilation and decomposition are required for 48 hours to ensure that the residual ethylene oxide content is ≤10μg / g.

[0108] Finally, it should be noted that the above embodiments are merely examples for the purpose of illustrating the present invention and are not intended to limit the embodiments. Those skilled in the art will readily appreciate that other variations or modifications based on the above description are possible. It is not necessary and impossible to provide an exhaustive list of all embodiments. However, obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. An eye ointment for relieving visual fatigue, characterized in that: The composition comprises the following components in parts by weight: Morin-rosmarinic acid nanomicelles: 2.5-3.5 parts; Ginsenoside Rg3-rutin microcapsules: 2.0-2.4 parts; Capsaicin-cyclodextrin-hydroxypropyl methylcellulose inclusion gel: 4.5-5.5 parts; Nano-silica aerogel-sodium hyaluronate moisturizing particles: 0.6-1.0 parts; Olive oil-shea butter-carnauba wax composite matrix: 65.0-68.0 parts; Gellan gum-xanthan gum-guar gum composite hydrogel: 22.0-23.0 parts.

2. The eye protection ointment for relieving visual fatigue according to claim 1, wherein The morin-rosmarinic acid nano-micelles are prepared by a self-assembly method using 6.0 parts of 20% poloxamer 407 and 2.4 parts of 8% cholesterol as carrier materials, with an average particle size of 55±3 nm and an encapsulation rate of not less than 93%.

3. The eye protection ointment for relieving visual fatigue according to claim 1, wherein The ginsenoside Rg3-rutin microcapsules are prepared using sodium alginate and chitosan as wall materials through an emulsification-crosslinking method, with an average particle size of 200±10nm and an encapsulation rate of ≥91%. The sodium alginate accounts for 1.8% of the total mass of the microcapsules, and the chitosan accounts for 1.5% of the total mass of the microcapsules.

4. The eye protection ointment for relieving visual fatigue according to claim 1, wherein The capsaicin-cyclodextrin-hydroxypropyl methylcellulose inclusion gel is prepared by freeze-drying capsaicin and cyclodextrin at a molar ratio of 1:1.2, and then adding hydroxypropyl methylcellulose solution to form the inclusion gel at 45° C. and an ultrasonic power of 250W for 15 minutes.

5. The eye protection ointment for relieving visual fatigue according to claim 1, wherein The nano-silica aerogel-sodium hyaluronate moisturizing particles are prepared by mixing nano-silica aerogel prepared by a sol-gel method using ethyl orthosilicate as a precursor with sodium hyaluronate in a mass ratio of 3:1, and dispersing the mixture at a stirring speed of 700 rpm and a temperature of 40° C. for 20 minutes.

6. The eye protection ointment for relieving visual fatigue according to claim 1, wherein The olive oil-shea butter-carnauba wax composite matrix is ​​prepared by mixing 52.0 parts of olive oil, 33.0 parts of shea butter, and 15.0 parts of carnauba wax according to a mass ratio, and melting and stirring the mixture in a 75° C. water bath at a stirring speed of 300 rpm to obtain the resultant mixture.

7. The eye protection ointment for relieving visual fatigue according to claim 1, wherein The gellan gum-xanthan gum-guar gum composite hydrogel is formed by mixing 38.0 parts of gellan gum, 32.0 parts of xanthan gum and 30.0 parts of guar gum according to a mass ratio, adding deionized water, heating to 80° C. to fully dissolve, and cooling.

8. A method for preparing the eye ointment for relieving visual fatigue according to any one of claims 1 to 7, characterized in that: The following steps are involved: S1: Preparation of active ingredient carriers, including morin-rosmarinic acid nanomicelles and ginsenoside Rg3-rutin microcapsules; S2: Preparation of functional excipients, including capsaicin-cyclodextrin-hydroxypropyl methylcellulose inclusion gel and nano-silica aerogel-sodium hyaluronate moisturizing microparticles; S3: melting and mixing the matrices to prepare an olive oil-shea butter-carnauba wax composite matrix and a gellan gum-xanthan gum-guar gum composite hydrogel, respectively, and mixing the two to form a composite matrix; S4: Composite optimization: the active ingredient carrier prepared in S1 and the functional excipient prepared in S2 were sequentially added to the composite matrix prepared in S3, and mixed at 40°C and 300 rpm for 1.5 hours to ensure uniform dispersion of the ingredients; S5: Product molding and quality inspection: fill the evenly mixed eye ointment into aluminum-plastic soft tubes, each with a capacity of 15g, and conduct particle size and potential detection, rheological property testing, in vitro release determination and stability investigation.

9. An eye patch composition comprising the eye ointment for relieving visual fatigue according to any one of claims 1 to 7, characterized in that: The eye ointment accounts for 25% of the total mass of the eye patch. The base material is non-woven fabric and the packaging material is aluminum foil composite film.

Images