Eye pad for relieving eye fatigue

Abstract

The application relates to the technical field of traditional Chinese medicine preparation, and discloses an eye patch for relieving eye fatigue, which is prepared from 200-350 parts of A group traditional Chinese medicine extract, 500-700 parts of B group traditional Chinese medicine extract, 2-8 parts of chitosan, 2-8 parts of sodium alginate, 30-90 parts of a penetration promoter and the rest of water, with the pH value being 4.5-5.5. The eye patch utilizes the electrostatic effect of chitosan and sodium alginate to form a colloid system with liquid-liquid phase separation structure, wherein the A group traditional Chinese medicine extract is wrapped in the composite coacervate droplets (dispersed phase), and the B group traditional Chinese medicine extract is distributed in the continuous phase. The specific microstructure and the step-by-step loading process realize the rapid release of the B group medicine to relieve the surface symptoms and the slow release of the A group medicine to deeply nourish, significantly prolong the drug retention time, and improve the bioavailability.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, and in particular to an eye patch for relieving eye fatigue. Background Technology

[0002] With the widespread use of electronic products and the fast pace of modern life, eye strain caused by excessive eye use has become a common phenomenon, often manifesting as symptoms such as dry eyes, eye irritation, redness, swelling, and blurred vision. Guided by traditional Chinese medicine theory, eye patches made by impregnating non-woven fabrics and other substrates with extracts of Chinese herbs have become an important means of relieving eye fatigue due to their convenient use and ability to directly target the affected area.

[0003] Currently, most commercially available herbal eye patches use traditional water extraction and alcohol precipitation processes to prepare the medicinal solution, and then directly adsorb all the herbal components onto the substrate after uniform mixing. While this preparation process is simple, it suffers from the technical drawback of difficulty in controlling drug release behavior. Existing eye patch solutions are typically simple homogeneous solution systems, with drug molecules primarily existing between the substrate fibers through physical adsorption. During use, drug release mainly relies on simple diffusion driven by the concentration gradient, often exhibiting a "burst release" characteristic—a large amount of drug is rapidly released at the initial stage of application, followed by a rapid decline in the release rate.

[0004] This single release mode is insufficient to meet the complex needs of eye care. On the one hand, for drugs that require rapid onset to relieve superficial symptoms such as redness and pain, burst release is acceptable; however, for tonifying drugs that require deep penetration to nourish the liver and kidneys and improve microcirculation, an excessively rapid release rate can lead to drug accumulation on the stratum corneum surface, preventing effective penetration, or loss within a short time, failing to maintain a long-lasting therapeutic concentration. On the other hand, simple aqueous solutions lack bioadhesion and have insufficient contact with the skin around the eyes, making them susceptible to moisture evaporation or facial movements, further reducing the transdermal absorption efficiency and bioavailability of the active ingredients in traditional Chinese medicine. Therefore, developing a novel eye patch drug delivery system that can balance rapid relief and long-lasting nourishment with good skin compatibility is a pressing issue in this field. Summary of the Invention

[0005] The technical problem solved by this invention is that existing Chinese herbal eye patches have a single drug release rate, which makes it difficult to meet the needs of quickly relieving eye discomfort and long-term nourishing and repairing, resulting in low bioavailability of active ingredients and short duration of action.

[0006] To address the above problems, the present invention provides the following technical solution:

[0007] In a first aspect, the present invention provides an eye patch for relieving eye fatigue, comprising a substrate and a liquid loaded on the substrate; the liquid, in 1000 parts by weight, is made from the following raw materials: 200-350 parts of a group A traditional Chinese medicine extract, 500-700 parts of a group B traditional Chinese medicine extract, 2-8 parts of chitosan, 2-8 parts of sodium alginate, 30-90 parts of a penetration enhancer, and the balance being water; wherein the pH value of the liquid is 4.5-5.5; the liquid is a colloidal system with a liquid-liquid phase separation structure, comprising a dispersed phase and a continuous phase; the chitosan and the sodium alginate form composite coagulated droplets through electrostatic interaction as the dispersed phase, the group A traditional Chinese medicine extract is encapsulated within the dispersed phase, and the group B traditional Chinese medicine extract is distributed in the continuous phase.

[0008] By employing the above technical solution, this invention utilizes the electrostatic complexation principle of natural polymer materials to construct a carrier system with biphasic release functionality. The specific mechanism and effects are described below:

[0009] First, a liquid-liquid phase separation system was constructed. The amino groups on the chitosan molecular chain protonate and become positively charged in a weakly acidic environment (pH 4.5–5.5), while the carboxyl groups on the sodium alginate molecular chain become negatively charged. When the two are mixed, the opposite charges attract each other electrostatically, causing the polymer chains to entangle and reducing the system's free energy, thus spontaneously causing phase separation. The system differentiates into a concentrated phase (dispersed / condensed phase) rich in polymeric complexes and a dilute phase (continuous / equilibrium phase) with extremely low polymer content.

[0010] Second, selective distribution of active ingredients is achieved. This invention employs a specific preparation process, allowing the herbal extracts of group A to enter the system before or during coagulation, thereby being physically embedded within the dispersed phase microdroplets by the high-density chitosan-sodium alginate three-dimensional network structure; while the herbal extracts of group B are added after the coagulation structure has formed and stabilized, and due to the steric hindrance effect of the network, they are mainly distributed in the low-density continuous phase solvent.

[0011] Third, it achieves a dual-stage release effect of "immediate release - sustained release". During use, the eye patch comes into contact with the skin:

[0012] Immediate release stage: The herbal extracts in group B, distributed in the continuous phase, are in a free or semi-free state, and can quickly penetrate the substrate to contact the skin and penetrate, rapidly exerting the immediate effects of clearing heat and dispersing nodules, and quickly relieving surface symptoms such as dry eyes and redness.

[0013] Sustained-release phase: Dispersed phase microdroplets adhere to the skin surface around the eyes due to the excellent bioadhesion of chitosan. Because of the dense polymer network, the release resistance of the herbal extracts from group A encapsulated within them is relatively high. With increased skin hydration and the influence of body temperature, the condensed phase microdroplets swell or undergo slight dissociation, allowing the drug to be slowly released through diffusion, thereby achieving deep nourishment and repair of the eye tissues.

[0014] In summary, this system loads different active ingredients of traditional Chinese medicine into two phases with different microstructures, which significantly prolongs the retention time of the active ingredients in the eye and improves the transdermal absorption efficiency and bioavailability of the drugs.

[0015] Preferably, the raw materials are in the following proportions by weight: 250-300 parts of herbal extract from group A, 550-650 parts of herbal extract from group B, 4-6 parts of chitosan, 4-6 parts of sodium alginate, 40-60 parts of glycerin, 1.5-2.5 parts of menthol, 0.8-1.2 parts of borneol, and the remainder being water.

[0016] By adopting the above technical solution, the proportions of each component are in optimal synergy. The ratio of chitosan to sodium alginate is close to the charge stoichiometric equilibrium point, resulting in uniform droplet size and stable structure in the formed condensed phase, with suitable drug loading and mechanical strength. The amount of penetration enhancer ensures both transdermal efficacy and avoids irritation to the skin around the eyes.

[0017] Preferably, the herbal extract in group A is prepared from the following raw materials: Scrophularia, Dendrobium, Angelica sinensis, Carthamus tinctorius, Buddleja officinalis, and Prunella vulgaris; the herbal extract in group B is prepared from the following raw materials: Cassia tora, Chrysanthemum indicum, Coptis chinensis, Scutellaria baicalensis, Gardenia jasminoides, Artemisia argyi, and Glycyrrhiza uralensis. More preferably, the weight ratio of each raw material in the herbal extract in group A is: Scrophularia tinctorius 200 parts, Dendrobium tinctorius 200 parts, Angelica sinensis 150 parts, Carthamus tinctorius 100 parts, Buddleja officinalis 100 parts, and Prunella vulgaris 100 parts; the weight ratio of each raw material in the herbal extract in group B is: Cassia tora 200 parts, Chrysanthemum indicum 200 parts, Coptis chinensis 100 parts, Scutellaria baicalensis 100 parts, Gardenia jasminoides 100 parts, Artemisia argyi 50 parts, and Glycyrrhiza uralensis 50 parts.

[0018] By adopting the above technical solution, the formulation was designed according to the traditional Chinese medicine theory of "treating the symptoms in acute cases and addressing the root cause in chronic cases." Group B consists mostly of bitter and cold herbs that clear heat (such as cassia seed and wild chrysanthemum), with a light and clear texture. Placing them in the continuous phase facilitates their rapid effect in clearing the liver and improving eyesight, reducing swelling and relieving pain. Group A consists mostly of herbs that nourish yin and blood, and promote blood circulation and remove blood stasis (such as scrophularia, dendrobium, and angelica), with a rich and moist texture. Placing them in the dispersed phase facilitates their slow release, allowing them to exert their root-cause-treating effects of nourishing the liver and kidneys, clearing away pterygium and improving eyesight. The drug properties and carrier release characteristics are matched, resulting in synergistic effects.

[0019] Preferably, the chitosan has a degree of deacetylation of 85.0% to 95.0% and a viscosity-average molecular weight of 1.5 × 10⁻⁶. 5 Up to 3.0×10 5 Da; The sodium alginate has a G / M ratio of 0.8 to 1.5 and a viscosity of 300 to 500 mPa·s.

[0020] By adopting the above technical solution, the physicochemical parameters of the polymer are defined. The high degree of deacetylation ensures that chitosan has sufficient positive charge density, which is conducive to forming a tight aggregate structure with sodium alginate; the suitable molecular weight range makes the formed liquid have appropriate viscosity, which is not only easy to coat onto the substrate, but also can form a good film-forming property and a good adherent feel on the skin surface.

[0021] Preferably, the preparation method of the herbal extract of group A or group B includes the following steps: mixing the raw materials and soaking them in water, heating and decocting at least twice, and combining the filtrates; concentrating the filtrate, cooling it, centrifuging at high speed to remove the precipitate, and taking the supernatant.

[0022] By adopting the above technical solution, high-concentration concentration and high-speed centrifugation processes are used to remove macromolecular impurities and insoluble particles from the drug solution, resulting in a high-concentration clarified extract (containing approximately 1 g / mL of raw drug). This prevents impurities from interfering with the polymer complex coagulation reaction and ensures the uniformity and stability of the system.

[0023] Preferably, the penetration enhancer is selected from one or a combination of several of glycerin, propylene glycol, menthol, and borneol.

[0024] By adopting the above technical solution, glycerin and propylene glycol, as moisturizers and solubilizers, help maintain the hydration state of the stratum corneum; menthol and borneol, as terpene penetration enhancers, can temporarily change the lipid structure of the stratum corneum, open skin channels, promote the transdermal absorption of macromolecular components of traditional Chinese medicine, and at the same time give the eye patch a cool and soothing sensory experience.

[0025] Secondly, the present invention provides a method for preparing an eye patch to relieve eye fatigue, comprising the following steps:

[0026] S1. Prepare the extracts of traditional Chinese medicine in group A and group B;

[0027] S2. Divide the herbal extract of group A into a first part and a second part, dissolve chitosan and sodium alginate in them respectively, and adjust the pH value to acidic to obtain a positively charged chitosan solution and a negatively charged sodium alginate solution respectively.

[0028] S3. Under stirring conditions, the sodium alginate solution is added dropwise to the chitosan solution, and the reaction forms a system D containing condensed phase droplets;

[0029] S4. Add the herbal extract and penetration enhancer from group B to system D, mix evenly, add water to make up the volume, homogenize and disperse, and let stand to mature to obtain the liquid.

[0030] S5. Load the liquid onto the substrate and encapsulate it.

[0031] By adopting the above technical solution, this invention utilizes a specific process route of "stepwise dissolution-composite coagulation-post-addition" to regulate the spatial distribution of different components in a colloidal system. The specific process principle and effects are as follows:

[0032] 1. In-situ embedding strategy:

[0033] This method does not employ the conventional approach of "preparing blank microcapsules before drug loading," but instead directly uses the extract of the traditional Chinese medicine in group A as a solvent to dissolve chitosan and sodium alginate separately. This operation ensures that the drug molecules of group A are uniformly dispersed in the polymer solution before the complex coagulation reaction occurs. When the positively charged chitosan solution and the negatively charged sodium alginate solution mix and undergo phase separation, the dispersed drugs of group A are captured in situ and encapsulated within the formed condensed phase (dispersed phase) microdroplets as the polymer chains contract and crosslink. This significantly improves the encapsulation efficiency and drug loading capacity of group A drugs.

[0034] 2. Structured step-by-step load:

[0035] The herbal extract in group B was added after system D (the suspension containing condensed phase droplets) had formed. At this point, chitosan and sodium alginate had already completed electrostatic complexation, forming a stable, dense network structure. Due to steric hindrance and network repulsion, the subsequently added group B drug could not easily penetrate the condensed phase droplets in large quantities, and therefore remained mainly in the continuous phase (external solvent environment). This stepwise addition process is key to constructing the specific microstructure of "group A embedded, group B free," thus achieving the biphasic release function of the drug.

[0036] 3. System stability control:

[0037] By controlling the dropping rate and stirring conditions, controlled liquid-liquid phase separation is induced in the system, avoiding the formation of large precipitates (liquid-solid separation). The resulting liquid is a heterogeneous colloidal system with thixotropic properties, facilitating subsequent coating and adhesion onto substrates.

[0038] Preferably, in step S2, the pH value is adjusted to 4.5-5.5 using a citric acid solution; in step S3, the stirring conditions are a rotation speed of 300-500 rpm and a temperature of 20-30°C.

[0039] By adopting the above technical solution, the reaction environment can be precisely controlled. The pH range of 4.5 to 5.5 is the optimal range for matching the charge density of chitosan and sodium alginate. Within this range, the degree of aggregation of the complex formed by the two is moderate, which can form a stable microdroplet structure without causing irreversible precipitation due to excessive charge. Controlling the stirring speed provides suitable shear force to prevent excessive aggregation of microdroplets in the aggregated phase and ensure the uniformity of the dispersed phase particle size.

[0040] Preferably, in step S4, the rotation speed of the homogenization dispersion is 800-1200 rpm, and the time is 5-8 minutes; the standing and ripening time is 2-4 hours.

[0041] By adopting the above technical solution, the homogenization process further refines the dispersed phase droplets through mechanical shearing force, and uniformly disperses the subsequently added B group extract and penetration promoter in the continuous phase to prevent excessively high local concentrations; the static aging step allows the polymer chain segments to fully relax and rearrange, eliminates the internal stress in the preparation process, and enables the colloidal system to reach a thermodynamically metastable state, ensuring the physical stability of the eye patch solution during storage and avoiding stratification or flocculation.

[0042] In summary, the present invention has at least one of the following beneficial technical effects:

[0043] 1. This invention constructs a specific microstructure with "dispersed phase encapsulation (Group A) and continuous phase distribution (Group B)" by controlling the electrostatic recombination reaction of chitosan and sodium alginate, combined with a stepwise loading process. This structure endows the eye patch with a clear two-stage release characteristic: the drug distributed in the continuous phase can be rapidly released to penetrate the stratum corneum and quickly relieve surface symptoms such as dryness and redness of the eyes; while the drug encapsulated in the dispersed phase microdroplets is slowly released with the dissociation or diffusion of the microdroplets, ensuring a continuous drug supply. This design effectively solves the problems of single drug release rate and short duration of action in traditional eye patches.

[0044] 2. This invention utilizes the positive charge and excellent bioadhesion of chitosan to enable the formed condensed phase microdroplets to adhere tightly to the negatively charged skin surface. Compared to ordinary liquid mixtures, this colloidal system with a liquid-liquid phase separation structure forms a more uniform and durable drug film on the skin surface around the eyes, significantly prolonging the retention time of the active ingredients at the application site, reducing drug loss, and thus improving the transdermal absorption efficiency and bioavailability of the active ingredients in traditional Chinese medicine.

[0045] 3. This invention achieves a perfect match between the carrier and the drug based on the characteristics of traditional Chinese medicine. Drugs with light and refreshing properties, primarily focused on clearing heat and resolving stagnation, are placed in the immediate-release phase, while drugs with rich and nourishing properties, primarily focused on tonifying and nourishing blood, are placed in the sustained-release phase. This spatial isolation not only avoids competitive absorption between different components but also conforms to the treatment principle of "treating the symptoms quickly and addressing the root cause gradually." This allows the two types of drug components to play a dominant role at different times, synergistically achieving comprehensive relief and repair of eye fatigue. Detailed Implementation

[0046] The present invention will be further described below with reference to specific embodiments:

[0047] The main raw materials and reagents used in the following examples and comparative examples have the following sources and specifications. Reagents not specifically mentioned are all commercially available analytical grade or higher grade products.

[0048] Chitosan (CAS No.: 9012-76-4), pharmaceutical grade, degree of deacetylation 85.0%–95.0%, viscosity-average molecular weight 1.5 × 10⁻⁶ 5 Up to 3.0×10 5 Sodium alginate (CAS No.: 9005-38-3), pharmaceutical grade, G / M ratio range 0.8–1.5, viscosity (1% aqueous solution, 20℃) 300–500 mPa·s, weight-average molecular weight 1.0 × 10⁻⁶. 5 Up to 2.5×10 5 Da.

[0049] Preparation Example 1:

[0050] This preparation example provides a Group A traditional Chinese medicine extract, including the following steps:

[0051] Weigh out 200g of Scrophularia, 200g of Dendrobium, 150g of Angelica sinensis, 100g of Carthamus tinctorius, 100g of Buddleja officinalis, and 100g of Prunella vulgaris. Mix them evenly and add 8500mL of deionized water. Soak at room temperature for 90 minutes. Heat to boiling and simmer for 90 minutes. Filter through a 200-mesh filter cloth and collect the first filtrate. Add 6800mL of deionized water to the dregs, heat to boiling and simmer for 60 minutes. Filter and collect the second filtrate. Combine the two filtrates and heat to concentrate to a volume of 850mL (corresponding to approximately 1g of raw herbs per 1mL of extract). Cool to room temperature and centrifuge at 5000rpm for 20 minutes. Collect the supernatant to obtain the clear extract of Group A Chinese herbal medicine.

[0052] Preparation Example 2:

[0053] This preparation example provides a Group B herbal extract, including the following steps:

[0054] Weigh out 200g of cassia seed, 200g of wild chrysanthemum, 100g of coptis, 100g of scutellaria, 100g of gardenia, 50g of mugwort, and 50g of licorice. Mix them evenly and add 8000mL of deionized water. Soak at room temperature for 60 minutes. Heat to boiling and simmer for 90 minutes. Filter through a 200-mesh filter cloth and collect the first filtrate. Add 6400mL of deionized water to the dregs, heat to boiling and simmer for 60 minutes. Filter and collect the second filtrate. Combine the two filtrates and heat to concentrate to a volume of 800mL (corresponding to approximately 1g of raw herbs per 1mL of extract). Cool to room temperature and centrifuge at 5000rpm for 20 minutes. Collect the supernatant to obtain the clear extract of Group B Chinese herbal medicine.

[0055] Example 1:

[0056] This embodiment provides a method for preparing an eye patch to relieve eye fatigue, including the following steps:

[0057] Take 300g of the herbal extract from Group A obtained in Preparation Example 1, and divide it into a first portion of 120g and a second portion of 180g. Add 5g of chitosan to the first portion of the extract, stir until completely dissolved, and adjust the pH to 5.0 using 1M citric acid solution to obtain a positively charged chitosan solution. Add 5g of sodium alginate to the second portion of the extract, stir until completely dissolved, and obtain a negatively charged sodium alginate solution.

[0058] Under stirring conditions of 25℃ and 400rpm, the above sodium alginate solution was added dropwise to the chitosan solution at a flow rate of 3mL / min using a peristaltic pump. After the addition was completed, stirring was continued for 10 minutes to obtain system D containing condensed phase droplets.

[0059] 600g of the herbal extract from group B obtained in Preparation Example 2 was slowly added to system D and stirred until homogeneous. Separately, 50g of glycerin, 2g of menthol and 1g of borneol were added, dissolved by sonication, and then added to the above mixed system. Deionized water was added to bring the total weight to 1000g.

[0060] Homogenize the mixture at 1000 rpm for 5 minutes, seal it, and let it stand at room temperature for 3 hours to mature. Take a non-woven fabric substrate, absorb the above liquid at a rate of 12g per piece, and package it to obtain the final product.

[0061] Example 2:

[0062] This embodiment provides a method for preparing an eye patch to relieve eye fatigue, including the following steps:

[0063] Take 200g of the herbal extract from Group A obtained in Preparation Example 1, and divide it into a first portion of 80g and a second portion of 120g. Add 2g of chitosan to the first portion of the extract, stir until completely dissolved, and adjust the pH to 4.8 using 1M citric acid solution to obtain a positively charged chitosan solution. Add 2g of sodium alginate to the second portion of the extract, stir until completely dissolved, and obtain a negatively charged sodium alginate solution.

[0064] Under stirring conditions of 20℃ and 300rpm, sodium alginate solution was added dropwise to chitosan solution at a flow rate of 2mL / min using a peristaltic pump to obtain system D;

[0065] 700g of the herbal extract from group B obtained in Preparation Example 2 was slowly added to system D and stirred until homogeneous. Separately, 30g of glycerin, 1g of menthol and 0.5g of borneol were added, dissolved by sonication, and then added to the above mixed system. Deionized water was added to bring the total weight to 1000g.

[0066] Homogenize the mixture at 800 rpm for 5 minutes, seal it, and let it stand at room temperature for 2 hours to mature. Take a Tencel film substrate, absorb the above liquid at a rate of 10g per piece, and then package it to obtain the final product.

[0067] Example 3:

[0068] This embodiment provides a method for preparing an eye patch to relieve eye fatigue, including the following steps:

[0069] Take 350g of the herbal extract from Group A obtained in Preparation Example 1, and divide it into a first portion of 140g and a second portion of 210g. Add 8g of chitosan to the first portion of the extract, stir until completely dissolved, and adjust the pH to 5.2 using 1M citric acid solution to obtain a positively charged chitosan solution. Add 8g of sodium alginate to the second portion of the extract, stir until completely dissolved, and obtain a negatively charged sodium alginate solution.

[0070] Under stirring conditions of 30℃ and 500rpm, sodium alginate solution was added dropwise to chitosan solution at a flow rate of 5mL / min using a peristaltic pump to obtain system D;

[0071] 500g of the herbal extract from group B obtained in Preparation Example 2 was slowly added to system D and stirred until homogeneous. Separately, 80g of glycerin, 3g of menthol and 1.5g of borneol were added, dissolved by sonication, and then added to the above mixed system. Deionized water was added to bring the total weight to 1000g.

[0072] The mixture was homogenized at 1200 rpm for 8 minutes, sealed, and allowed to stand at room temperature for 4 hours to mature. The hydrogel substrate was then taken, and the above liquid was absorbed into each piece at a rate of 15g. The substrate was then encapsulated.

[0073] Example 4:

[0074] This embodiment provides a method for preparing an eye patch to relieve eye fatigue, including the following steps:

[0075] Take 250g of the herbal extract from Group A obtained in Preparation Example 1, and divide it into a first portion of 100g and a second portion of 150g. Add 6g of chitosan to the first portion of the extract, stir until completely dissolved, and adjust the pH value to 4.5 using 1M citric acid solution to obtain a positively charged chitosan solution. Add 4g of sodium alginate to the second portion of the extract, stir until completely dissolved, and obtain a negatively charged sodium alginate solution.

[0076] Under stirring conditions of 25℃ and 350rpm, sodium alginate solution was added dropwise to chitosan solution at a flow rate of 3mL / min using a peristaltic pump to obtain system D;

[0077] 650g of the herbal extract from group B obtained in Preparation Example 2 was slowly added to system D and stirred until homogeneous. Separately, 40g of glycerin, 1.5g of menthol and 0.8g of borneol were added, dissolved by sonication, and then added to the above mixed system. Deionized water was added to bring the total weight to 1000g.

[0078] Homogenize the mixture at 900 rpm for 6 minutes, seal it, and let it stand at room temperature for 3 hours to mature. Take a non-woven fabric substrate, absorb the above liquid at a rate of 12g per piece, and package it to obtain the final product.

[0079] Example 5:

[0080] This embodiment provides a method for preparing an eye patch to relieve eye fatigue, including the following steps:

[0081] Take 300g of the herbal extract from Group A obtained in Preparation Example 1, and divide it into a first portion of 120g and a second portion of 180g. Add 4g of chitosan to the first portion of the extract, stir until completely dissolved, and adjust the pH to 5.5 using 1M citric acid solution to obtain a positively charged chitosan solution. Add 6g of sodium alginate to the second portion of the extract, stir until completely dissolved, and obtain a negatively charged sodium alginate solution.

[0082] Under stirring conditions of 25℃ and 400rpm, sodium alginate solution was added dropwise to chitosan solution at a flow rate of 4mL / min using a peristaltic pump to obtain system D;

[0083] 550g of the herbal extract from group B obtained in Preparation Example 2 was slowly added to system D and stirred until homogeneous. Separately, 60g of glycerin, 2.5g of menthol and 1.2g of borneol were added, dissolved by sonication, and then added to the above mixed system. Deionized water was added to bring the total weight to 1000g.

[0084] Homogenize the mixture at 1000 rpm for 5 minutes, seal it, and let it stand at room temperature for 3 hours to mature. Take a non-woven fabric substrate, absorb the above liquid at a rate of 12g per piece, and package it to obtain the final product.

[0085] Comparative Example 1:

[0086] Compared with Example 1, the difference is that chitosan and sodium alginate were not added, and no complex coagulation step was performed; the extracts of Group A, Group B, glycerin, menthol, and borneol were directly mixed, and 5g of carbomer (Carbomer 940) was added as a thickener. The pH was adjusted to 6.0 with triethanolamine to obtain a similar viscosity, and the rest were the same.

[0087] Comparative Example 2:

[0088] Compared with Example 1, the difference lies in the change of the feeding sequence and coagulation method, and the step-by-step loading process was not adopted. Specifically, the extracts of Group A and Group B were first mixed evenly, and then the mixture was divided into two parts. Chitosan and sodium alginate were dissolved in each part, and the pH was adjusted to 5.0 before being added dropwise and mixed, so that all medicinal components were randomly and uniformly embedded in the condensed phase, and everything else was the same.

[0089] Comparative Example 3:

[0090] Compared to Example 1, the difference lies in the substitution of the groups of medicinal extracts. Specifically, when preparing polymer solutions B and C, extract group B (adjuvant drugs) is used instead of extract group A for dissolution and coagulation; in the subsequent mixing steps, extract group A (principal and assistant drugs) is added as the continuous phase, thus achieving a reverse loading design where drug group B is encapsulated and drug group A is free. All other aspects remain the same.

[0091] Comparative Example 4:

[0092] Compared to Example 1, the difference is that only 5g of chitosan was added, and sodium alginate was not added. After dissolving chitosan in the extract of Group A and adjusting the pH to 5.0, it was directly mixed with the extract of Group B and excipients. Only the cationic polymer in the system exists, and it cannot form a liquid-liquid phase separation condensed droplet structure. Everything else is the same.

[0093] Comparative Example 5:

[0094] The difference compared to Example 1 is that the pH of the system was adjusted to 7.0. Under this pH condition, chitosan undergoes deprotonation and becomes uncharged, unable to generate electrostatic attraction with sodium alginate, resulting in the inability to undergo a complex coagulation reaction. Consequently, flocculent precipitates rather than stable condensed phase droplets appear in the system, while everything else remains the same.

[0095] Test Example 1:

[0096] The experimental method is as follows:

[0097] (1) Turbidity (transmittance) test: Take appropriate amounts of fresh liquids prepared in Examples 1-5 and Comparative Examples 1, 4, and 5, and use deionized water as a reference to measure their transmittance (T%) at a wavelength of 600 nm using a UV-Vis spectrophotometer. The lower the transmittance, the higher the turbidity of the system, suggesting that a large number of micro-aggregates or condensed phase droplets may have formed.

[0098] (2) Zeta potential test: Take the above samples and dilute them with deionized water to an appropriate multiple (about 100 times). Measure their surface potential using a Zeta potential analyzer at 25°C. Each sample was measured in parallel three times, and the average value was taken. This index is used to reflect the degree of neutralization of positive and negative charges in the system and the electrostatic stability of the colloidal dispersion.

[0099] (3) Centrifugal stability test: Take 10 mL of each of the above groups of samples and place them in centrifuge tubes, and record the initial height H0. Place them in a high-speed centrifuge, set the speed to 3000 rpm, and centrifuge for 20 minutes. After centrifugation, observe whether there is precipitation or stratification at the bottom of the tube. If there is precipitation, measure the height H of the precipitation layer and calculate the precipitation rate (H / H0×100%); if there is no obvious precipitation, record it as "<1%". This index is used to distinguish between stable colloidal dispersion systems and unstable coarse precipitates.

[0100] The test results of the physicochemical parameters of each group of samples are shown in Table 1.

[0101] Table 1. Colloidal properties and stability test data of each example and comparative example:

[0102]

[0103] Based on the data in Table 1, the colloidal behavior of each system is analyzed as follows:

[0104] The transmittance of Examples 1-5 was significantly lower than that of Comparative Examples 1 and 4, ranging from 8% to 29%. This indicates that significant phase separation occurred in the system under suitable pH conditions with the coexistence of chitosan and sodium alginate, resulting in a large number of micron-sized light scatterers. Zeta potential tests showed that the absolute values ​​of the potentials in the Example groups were all relatively small (between -5.1 mV and +4.5 mV), close to the isoelectric point region. This confirms that a sufficient electrostatic neutralization reaction occurred between the positively charged chitosan and the negatively charged sodium alginate, forming a polyelectrolyte complex with a low charge density. Furthermore, except for Example 3, which showed slight sedimentation due to the high polymer concentration, the centrifugal sedimentation rates of the other examples were all less than 1%, exhibiting good kinetic stability. This indicates that the formed complex is not an unstable coarse flocculent, but rather a series of tiny droplets (condensed phase) stably dispersed in a continuous phase.

[0105] In contrast, Comparative Example 1 (physical mixture) and Comparative Example 4 (single polymer) both had transmittance exceeding 90%, clear appearance, and strong negative (Comparative Example 1, derived from sodium alginate or matrix) or positive (Comparative Example 4, derived from chitosan) Zeta potentials, indicating that the system was in a molecularly dissolved state and no macromolecular assembly or aggregation had occurred.

[0106] Although Comparative Example 5 showed a decrease in transmittance (65.8%), indicating turbidity, its centrifugal precipitation rate was as high as 15.6%, and its Zeta potential was negative (-22.3 mV). This is because, under pH 7.0 conditions, chitosan deprotonates, resulting in the loss of its positive charge and preventing it from binding with sodium alginate via electrostatic interactions. The turbidity observed at this point mainly stems from the precipitation of chitosan under alkaline conditions, rather than the formation of a structurally ordered liquid-liquid condensate, and therefore lacks the physical stability required to resist centrifugation.

[0107] In summary, the examples successfully induced stable liquid-liquid phase separation (composite coagulation) by controlling pH and polymer ratio, thus constructing the expected micro-reservoir structure, while none of the comparative examples achieved this specific colloidal structure.

[0108] Test Example 2:

[0109] The experimental method is as follows:

[0110] (1) Diffusion apparatus and membrane material: A vertical Franz diffusion cell was used. Ex vivo pig ear skin that met the experimental requirements was selected, subcutaneous fat and connective tissue were removed, and the skin was washed with physiological saline to serve as a transdermal barrier membrane. The skin was fixed between the supply chamber and the receiving chamber, with the stratum corneum facing the supply chamber.

[0111] (2) Receiving solution and conditions: The receiving chamber is filled with phosphate buffer (PBS, pH 7.4) and the temperature is maintained at 32±0.5℃ by circulating water bath to simulate the temperature of human skin surface. The receiving solution is continuously stirred with a magnetic stir bar (300 rpm) to eliminate diffusion layer resistance.

[0112] (3) Sample administration and sampling: Weigh 1.0 g of each of the samples prepared in Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 3, and spread them evenly on the skin surface of the supply chamber side. At time points of 0.5 h, 1 h, 2 h, 4 h and 8 h after administration, respectively, draw 2.0 mL of solution from the receiving chamber side opening, and immediately add an equal volume of blank PBS buffer at the same temperature.

[0113] (4) Content determination: After the extracted samples were filtered through a 0.45 μm microporous membrane, the concentrations of harbazoside and chlorogenic acid in the filtrate were determined by high performance liquid chromatography (HPLC). Based on the measured concentrations and dilution factors, the cumulative permeate at each time point was calculated and converted into the cumulative release percentage (%). Each group of samples was measured in triplicate, and the average value was taken.

[0114] The cumulative release percentage of the index components in each group of samples over time is shown in Table 2.

[0115] Table 2. Cumulative in vitro release rates (%) of harbazoside and chlorogenic acid under different process conditions:

[0116]

[0117] According to the data in Table 2, Example 1 and the comparative examples exhibit different drug release kinetic characteristics.

[0118] Comparative Example 1 employed a direct mixing process without constructing any microscopic barrier structures. Data showed that the release behavior of chlorogenic acid and harpaquinone was essentially synchronized, both reaching release rates exceeding 35% within 0.5 hours, demonstrating rapid release of both components. This indicates that in ordinary gel matrices, solute diffusion is primarily driven by concentration gradients, lacking the ability to retain specific components.

[0119] Comparative Example 2 employed a coagulation process after full-component mixing. The results showed that the release rates of chlorogenic acid and harpaquinone were both below 6% at 0.5 hours, and the subsequent release rates were significantly lower than in Comparative Example 1. This phenomenon confirms that the coagulated phase formed by chitosan and sodium alginate has a dense network structure, which can significantly hinder the diffusion of encapsulated molecules. However, because this process did not differentiate the loading, the B component (chlorogenic acid), which should have a rapid onset of action, was also confined within the coagulated phase, failing to meet the requirement for rapid release.

[0120] Comparative Example 3 involved swapping the loading targets (Group A in the continuous phase, Group B in the condensed phase). The data showed the opposite trend to Example 1: harbazoside (Group A) exhibited rapid release characteristics, while chlorogenic acid (Group B) showed slow release. This result, conversely, validates the effectiveness of the stepwise loading process, namely that the retardation effect of the condensed phase is targeted at the loaded target.

[0121] Data from Example 1 shows that chlorogenic acid achieved a release rate of 36.4% within 0.5 hours, similar to Comparative Example 1, indicating that component B is mainly distributed in the continuous phase and is not subject to diffusion limitations in the condensed phase, allowing for rapid penetration. In contrast, harbazoside's release rate was only 4.2% at 0.5 hours, followed by a steady increase to 79.8% at 8 hours. This "hysteresis followed by steady release" characteristic indicates that component A is effectively encapsulated within dispersed condensed phase droplets. Drug molecules must first diffuse from the high-viscosity condensed phase to the continuous phase, and then penetrate the matrix to enter the interface; this dual diffusion process creates the sustained-release effect.

[0122] In summary, through a specific stepwise composite coagulation process, Example 1 successfully constructed a delivery system with a two-phase release function, realizing a kinetic combination of rapid release of component B and sustained release of component A.

[0123] Test Example 3:

[0124] The experimental method is as follows:

[0125] (1) Instruments and equipment: texture analyzer (equipped with a 5kg force sensor), P / 0.5 cylindrical stainless steel probe.

[0126] (2) Simulated matrix: Fresh pig back skin was selected, the subcutaneous fat layer and hair were removed, the surface was cleaned with physiological saline, and it was cut into 2.5cm×2.5cm squares as the biological matrix to simulate human skin. The pig skin was fixed on the pressure platform of the texture apparatus with the stratum corneum facing upward, and equilibrated in a constant temperature and humidity chamber for 30 minutes (32℃, RH 60%) before the experiment.

[0127] (3) Sample preparation: The eye patch liquid prepared in Examples 1 to 5 and Comparative Examples 1, 4 and 5 were coated onto circular test pieces (20 mm in diameter) with a coating thickness of 1.0 mm.

[0128] (4) Test procedure: The probe retraction method is used.

[0129] The test probe descends at a speed of 1.0 mm / s until the test piece with the sample attached is in complete contact with the pigskin surface.

[0130] Maintain the contact pressure (trigger force) at 0.5N and hold the contact time for 30 seconds to ensure that the interface is fully wetted.

[0131] The test probe is raised at a speed of 2.0 mm / s until the sample is completely separated from the pigskin.

[0132] (5) Data acquisition: The instrument automatically records the force-displacement curve during the probe lifting process. The maximum positive peak value is calculated as the maximum adhesion force (N), and the area under the force-displacement curve is calculated as the adhesion work (mJ). Each group of samples is tested in parallel 5 times, and the average value and standard deviation of the results are taken.

[0133] The bioadhesion performance test data of each group of samples are shown in Table 3.

[0134] Table 3. Bioadhesion and adhesion work test data of each group of eye patch samples:

[0135]

[0136] Based on the data in Table 3, the various embodiments and comparative examples showed significant differences in bioadhesion performance, as detailed below:

[0137] The maximum adhesive forces in Examples 1-5 ranged from 0.71 to 1.15 N, and the adhesive work ranged from 4.15 to 6.88 mJ, both significantly higher than those in Comparative Example 1 (0.38 N, 1.85 mJ). This difference stems from the structural characteristics of the polymer materials. The carbomer used in Comparative Example 1 mainly forms a physical gel with water through hydrogen bonds. Its interaction with the stratum corneum of the skin is limited to van der Waals forces and weak hydrogen bonds, and its interfacial wettability is limited. Therefore, it is prone to interfacial delamination under stress.

[0138] In contrast, the example group introduced a chitosan-sodium alginate composite condensation system. The chitosan molecular chain is rich in primary amino groups, which undergo protonation (-NH3) in a weakly acidic environment of pH 4.5–5.5. + The stratum corneum and mucins on the skin surface typically carry negative charges (such as sialic acid residues), resulting in electrostatic attraction between them and significantly enhancing interfacial bonding. Furthermore, the composite condensed phase is a high-molecular-weight liquid phase that, compared to a rigid gel network, exhibits better flexibility and fluidity, allowing it to penetrate into the microscopic grooves of the skin surface, increasing the effective contact area and thus enhancing the mechanical interlocking effect.

[0139] The data from Comparative Example 5 (0.24 N, 0.96 mJ) further confirmed the crucial role of electrostatic interaction. Under pH 7.0 conditions, chitosan deprotonated, its positive charge disappeared, and it not only lost its electrostatic adsorption capacity with the skin but also underwent phase separation and precipitation due to reduced solubility. The precipitated particles acted as a "lubricant" at the interface, hindering the contact between the continuous phase and the skin, resulting in a minimum level of adhesion.

[0140] Although Comparative Example 4 contains chitosan and exhibits some adhesion (0.78 N), it is lower than that of Example 1. This indicates that while pure dissolved chitosan possesses electrostatic adsorption capabilities, it lacks the high viscoelasticity characteristic of composite condensed phases. The microdroplet condensed phase formed in Example 1, through the cross-linking effect of sodium alginate, constructs an internal network with a certain strength, which can dissipate more energy during stretching (manifested as higher adhesion work), thereby achieving a more durable retention effect.

[0141] Test Example 4:

[0142] The experimental method is as follows:

[0143] (1) Recruitment of subjects: 40 healthy volunteers aged between 20 and 45 years (20 males and 20 females) were recruited. The inclusion criteria were: people who use their eyes heavily every day (average daily screen time > 6 hours), who recently reported symptoms of dry and tired eyes, and who had no history of broken or allergic skin around their eyes.

[0144] (2) Grouping and drug administration: Volunteers were randomly divided into 4 groups of 10 each. Each group used samples from Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 3 respectively. Before the experiment, the samples were uniformly de-identified and coded.

[0145] (3) Evaluation procedure: After the volunteers cleaned their faces, eye patches were applied to the area around their eyes.

[0146] Immediate cooling sensation evaluation: Within 15 minutes after application, volunteers rated the intensity of the cooling sensation around the eyes based on their subjective feelings.

[0147] Evaluation of lasting hydration: After 30 minutes of application, the eye patch was removed and the patient moved around naturally. Four hours after removing the eye patch, volunteers rated the degree of hydration and relief of tightness around the eyes.

[0148] (4) Scoring criteria: The 0-10 point visual simulation scoring method is adopted.

[0149] Instant cooling sensation: 0 points indicates no cooling sensation, and 10 points indicates a strong cooling and soothing sensation.

[0150] Long-lasting hydration: 0 points indicates dry and tight skin, while 10 points indicates hydrated, soft skin without any tightness.

[0151] (5) Data processing: Calculate the average and standard deviation of the scores for each group.

[0152] The sensory evaluation statistics of each group of volunteers are shown in Table 4.

[0153] Table 4. Statistical analysis of human sensory evaluation scores for eye patch samples from different processes (n=10):

[0154]

[0155] According to the data in Table 4, the sensory scores of each group of samples showed significant structural differences, which is consistent with the results of in vitro release and physical characterization.

[0156] Comparative Example 1 scored highest (9.1) for "immediate cooling sensation" but lowest (3.2) for "long-lasting moisturizing sensation." This is typical of ordinary solution-type formulations. Because all ingredients (including menthol and Group B extract) are dissolved in the continuous phase and there is no slow-release carrier to impede release, the active substances are released in large quantities upon contact with the skin, producing a strong cooling sensation. However, this explosive release leads to the depletion of the active ingredients in a short time, and the lack of a film-forming and water-retaining effect formed by condensed phase droplets on the skin surface results in a significant decrease in moisturizing sensation after 4 hours, failing to meet the needs of long-lasting skincare.

[0157] The rating trend in Comparative Example 2 was exactly the opposite: the "immediate cooling sensation" score was low (3.4), while the "long-lasting moisturizing sensation" was acceptable (7.6). Because this group used a full-component encapsulation process, the small-molecule volatile oil (menthol) responsible for producing the cooling sensation and the B-group drug were sealed inside a dense condensed phase. This resulted in high diffusion resistance, making it difficult to reach the onset threshold in a short time, leading to a user experience of "slow onset" or "no sensation." Although the presence of the condensed phase maintained the moisturizing effect in the later stages, the lack of the initial soothing experience resulted in an overall poor effect.

[0158] All indicators in Comparative Example 3 were at low levels. This group encapsulated the B component, which should have been released immediately, resulting in insufficient cooling sensation (4.1); at the same time, the A component, which should have been released slowly and nourishingly, was placed in the continuous phase, causing it to be lost prematurely and failing to maintain long-lasting moisturizing effect (3.8). This result proves that if the pharmacological grouping and the carrier structure are not compatible, it will lead to the complete failure of product function.

[0159] Example 1 exhibited the best overall performance. Its "Instant Cooling Sensation" score was 8.7, close to Comparative Example 1, indicating that the B component and penetration enhancer distributed in the continuous phase were not hindered and could quickly penetrate the stratum corneum to exert an emergency soothing effect. Meanwhile, its "Long-lasting Moisturizing Sensation" score was 8.4, significantly higher than Comparative Examples 1 and 3. This is attributed to two mechanisms: first, the nourishing components of group A are encapsulated in condensed phase microdroplets, releasing slowly along the concentration gradient; second, the positively charged chitosan condensed phase microdroplets undergo bioadhesion on the skin surface, forming a biomimetic hydration film that reduces transepidermal water loss.

[0160] In summary, Example 1 successfully achieved the synergy of "rapid cooling and itch relief" and "long-lasting moisturizing and nourishing" at the human sensory level by constructing a two-phase dynamic system of "continuous phase rapid release - dispersed phase sustained release", thus verifying the effectiveness of the technical solution.

[0161] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. An eye patch for relieving eye fatigue, characterized in that, Includes a substrate and a liquid loaded on the substrate; The liquid solution, based on 1000 parts, is made from the following raw materials in parts by weight: Group A: 200-350 parts of herbal extract; Group B: 500-700 parts of herbal extract; Chitosan: 2-8 parts; Sodium alginate: 2-8 parts; Permeability enhancer: 30-80 parts; Water: balance. The pH value of the feed solution is 4.5 to 5.5; the feed solution is a colloidal system with a liquid-liquid phase separation structure, including a dispersed phase and a continuous phase; the chitosan and the sodium alginate form composite coagulated droplets through electrostatic interaction as the dispersed phase, the herbal extract of group A is encapsulated inside the dispersed phase, and the herbal extract of group B is distributed in the continuous phase.

2. The eye patch for relieving eye fatigue according to claim 1, characterized in that, The weight parts of the raw materials are: Group A: 250-300 parts of herbal extract; Group B: 550-650 parts of herbal extract; Chitosan: 4-6 parts; Sodium alginate: 4-6 parts; Glycerin: 40-60 parts; Menthol: 1.5-2.5 parts; Borneol: 0.8-1.2 parts; Water: balance.

3. The eye patch for relieving eye fatigue according to claim 1, characterized in that, The herbal extract in Group A is prepared from the following raw materials: Scrophularia, Dendrobium, Angelica sinensis, Carthamus tinctorius, Buddleja officinalis, and Prunella vulgaris; The herbal extract in Group B is prepared from the following raw materials: cassia seed, wild chrysanthemum, coptis, scutellaria, gardenia, mugwort, and licorice.

4. The eye patch for relieving eye fatigue according to claim 3, characterized in that, The weight ratio of each raw material in the herbal extract of Group A is as follows: 200 parts of Scrophularia ningpoensis, 200 parts of Dendrobium nobile, 150 parts of Angelica sinensis, 100 parts of Carthamus tinctorius, 100 parts of Buddleja officinalis, and 100 parts of Prunella vulgaris. The weight ratio of each raw material in the herbal extract of Group B is as follows: 200 parts of cassia seed, 200 parts of wild chrysanthemum, 100 parts of coptis, 100 parts of scutellaria, 100 parts of gardenia, 50 parts of mugwort, and 50 parts of licorice.

5. The eye patch for relieving eye fatigue according to claim 1, characterized in that, The chitosan has a degree of deacetylation of 85.0%–95.0% and a viscosity-average molecular weight of 1.5 × 10⁻⁶. 5 Up to 3.0×10 5 Da; The sodium alginate has a G / M ratio of 0.8 to 1.5 and a viscosity of 300 to 500 mPa·s.

6. The eye patch for relieving eye fatigue according to claim 3, characterized in that, The preparation method of the herbal extract from group A or group B includes the following steps: Mix the raw materials, soak them in water, heat and boil them at least twice, and combine the filtrates. Concentrate the filtrate, cool it, and centrifuge it at high speed to remove the precipitate. Take the supernatant to obtain the final product.

7. The eye patch for relieving eye fatigue according to claim 1, characterized in that, The penetration enhancer is selected from one or a combination of several of glycerin, propylene glycol, menthol, and borneol.

8. A method for preparing an eye patch for relieving eye fatigue as described in any one of claims 1-7, characterized in that, Includes the following steps: S1. Prepare the extracts of traditional Chinese medicine in group A and group B; S2. Divide the herbal extract of group A into a first part and a second part, dissolve chitosan and sodium alginate in them respectively, and adjust the pH value to acidic to obtain a positively charged chitosan solution and a negatively charged sodium alginate solution respectively. S3. Under stirring conditions, the sodium alginate solution is added dropwise to the chitosan solution, and the reaction forms a system D containing condensed phase droplets; S4. Add the herbal extract and penetration enhancer from group B to system D, mix evenly, add water to make up the volume, homogenize and disperse, and let stand to mature to obtain the liquid. S5. Load the liquid onto the substrate and encapsulate it.

9. The preparation method according to claim 8, characterized in that, In step S2, the pH value is adjusted to 4.5-5.5 using a citric acid solution; in step S3, the stirring conditions are a speed of 300-500 rpm and a temperature of 20-30°C.

10. The preparation method according to claim 8, characterized in that, In step S4, the rotation speed of the homogenization dispersion is 800-1200 rpm, and the time is 5-8 minutes; the standing and ripening time is 2-4 hours.

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