A traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents and a preparation method thereof

Abstract

This invention provides a herbal hydrogel eye patch for preventing and treating myopia in adolescents and its preparation method. The patch includes at least a hydrogel layer loaded with herbal extracts. The herbal extracts include the following ingredients: Salvia miltiorrhiza, Angelica sinensis, Lycium barbarum, Buddleja officinalis, Ligusticum chuanxiong, Lonicera japonica, Vaccaria segetalis, Astragalus membranaceus, and Glycyrrhiza uralensis. The matrix of the hydrogel layer includes the following ingredients in parts by weight: poloxamer 20-25 parts, sphingomyelin 2.0-4.0 parts, sodium glycerophosphate 1.5-2.0 parts, sodium phytate 0.5-0.8 parts, modified chitosan 1.0-2.0 parts, and sodium pyrrolidone carboxylate 0.5-1.0 parts. This herbal hydrogel eye patch for preventing and treating myopia in adolescents can improve the discomfort symptoms of myopia patients and effectively prevent and treat myopia in adolescents.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a hydrogel eye patch made of traditional Chinese medicine for the prevention and treatment of myopia in adolescents and its preparation method. Background Technology

[0002] Myopia is a common eye disease characterized by elongation of the eye axis and increased refractive power. In recent years, the incidence of myopia among adolescents has been rising continuously, showing characteristics of younger age and more severe severity, and has become a major public health problem affecting national eye health. Currently, clinical methods for preventing and treating myopia in adolescents mainly include optical correction (such as eyeglasses and orthokeratology lenses), drug intervention, and behavioral intervention. However, existing intervention methods all have certain limitations: eyeglasses can only correct vision but cannot slow down the progression of myopia; orthokeratology lenses have strict requirements for hygiene and pose a risk of corneal infection; although low-concentration atropine eye drops have been proven to slow down the progression of myopia, long-term use may cause side effects such as photophobia, blurred near vision, and allergic reactions, and the eye drop formulation has shortcomings such as rapid drug loss and low bioavailability.

[0003] In recent years, the application of traditional Chinese medicine (TCM) in the prevention and treatment of myopia has gradually attracted attention. TCM believes that the occurrence of myopia is closely related to liver and kidney deficiency, qi and blood deficiency, and insufficient nourishment of the eyes. Treatment often employs methods to nourish the liver and kidneys, replenish qi and blood, and improve vision and remove corneal opacity. However, traditional external TCM preparations (such as eye ointments, eye washes, and eye patches) generally suffer from low transdermal absorption efficiency, making it difficult to achieve continuous and effective drug delivery.

[0004] Hydrogels, as a type of three-dimensional network structure polymer material, possess excellent biocompatibility, tunable mechanical properties, and drug release behavior, showing broad application prospects in the field of transdermal drug delivery. However, existing hydrogel systems have limited drug loading capacity, making it difficult to achieve effective loading and release of active ingredients from traditional Chinese medicine. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents and its preparation method, so as to solve the problem that the drug loading capacity of the existing traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents is limited and cannot fully exert its efficacy.

[0006] This invention provides the following technical solution: A hydrogel eye patch made of traditional Chinese medicine for preventing and treating myopia in adolescents, comprising at least a hydrogel layer loaded with extracts of traditional Chinese medicine; The herbal extract includes the following raw materials: Salvia miltiorrhiza, Angelica sinensis, Lycium barbarum, Buddleja officinalis, Ligusticum chuanxiong, Lonicera japonica, Vaccaria segetalis, Astragalus membranaceus, Glycyrrhiza uralensis; The matrix of the hydrogel layer comprises the following raw materials in parts by weight: Poloxamer 20-25 parts, sphingomyelin 2.0-4.0 parts, sodium glycerophosphate 1.5-2.0 parts, sodium phytate 0.5-0.8 parts, modified chitosan 1.0-2.0 parts, sodium pyrrolidone carboxylate 0.5-1.0 parts.

[0007] In some embodiments, the herbal extract comprises the following raw materials in parts by weight: 80-90 parts of Salvia miltiorrhiza, 55-65 parts of Angelica sinensis, 50-60 parts of Lycium barbarum, 45-55 parts of Buddleja officinalis, 35-45 parts of Ligusticum chuanxiong, 35-45 parts of Lonicera japonica, 25-35 parts of Vaccaria segetalis, 20-30 parts of Astragalus membranaceus, and 8-12 parts of Glycyrrhiza uralensis.

[0008] Among them, Danshen (Salvia miltiorrhiza) is bitter in taste and slightly cold in nature. It enters the heart and liver meridians and has the effects of promoting blood circulation and removing blood stasis, regulating menstruation and relieving pain, clearing the heart and relieving irritability. It can dilate microvessels and improve microcirculation in the eyes.

[0009] Angelica sinensis has a sweet and pungent taste, is warm in nature, and enters the liver, heart, and spleen meridians. It has the effects of nourishing blood and promoting blood circulation, regulating menstruation and relieving pain, and moistening the intestines and promoting bowel movements.

[0010] Goji berries are sweet in taste and neutral in nature. They enter the liver and kidney meridians and have the effects of nourishing the liver and kidneys, benefiting essence and improving eyesight. They are rich in goji polysaccharides, which can nourish the optic nerve and improve the vitality of retinal cells.

[0011] Buddleja officinalis has a sweet taste and slightly cold nature. It enters the liver meridian and has the effects of clearing heat and nourishing the liver, improving eyesight and removing corneal opacity. It can be used to treat red eyes due to liver heat, excessive tearing, photophobia, and blurred vision.

[0012] Chuanxiong (Ligusticum striatum) is pungent and warm in nature. It enters the liver, gallbladder, and pericardium meridians and has the effects of promoting blood circulation, regulating qi, dispelling wind, and relieving pain.

[0013] Honeysuckle has a sweet taste and cold nature. It enters the lung, heart, and stomach meridians and has the effects of clearing heat and detoxifying, dispersing wind-heat, and reducing inflammation of the eyelids and conjunctiva.

[0014] Blueberries, with their sour and sweet taste and cooling properties, nourish the liver and improve eyesight, have antioxidant effects, promote the regeneration of rhodopsin, and help relieve eye fatigue and improve dark adaptation.

[0015] Astragalus has a sweet taste and slightly warm nature. It enters the spleen and lung meridians and has the effects of tonifying qi and raising yang, consolidating the exterior and stopping sweating, and promoting diuresis and reducing swelling.

[0016] Licorice has a sweet taste and neutral properties. It enters the heart, lung, spleen, and stomach meridians and has the effects of tonifying the spleen and replenishing qi, clearing heat and detoxifying, relieving spasms and pain, and harmonizing the properties of other herbs.

[0017] In this invention, Danshen and Danggui are used as the principal herbs. Danshen is bitter and slightly cold, specifically entering the blood level, promoting blood circulation, removing blood stasis, and clearing the eye meridians, which helps improve the ciliary muscle's blood stasis, spasm, and pain caused by prolonged visual strain. Danggui is sweet, pungent, and warm, nourishing and promoting blood circulation, and moisturizing the liver and eyes, which helps improve blurred vision and dry eyes caused by prolonged visual strain depleting liver blood and deficiency of qi and blood around the eyes in adolescents. The combination of the two herbs, one promoting blood circulation and the other nourishing, one cold and the other warm, avoids both simply promoting blood circulation and damaging the blood, and also prevents blood stasis from being caused by simply nourishing the blood, thus taking into account both anti-inflammatory and swelling-reducing effects as well as nourishing qi and blood.

[0018] With wolfberry, buddleja officinalis, honeysuckle, and chuanxiong as assistant herbs, wolfberry, sweet and mild in nature, nourishes the yin of the liver and kidneys, replenishes the essence and blood depleted by prolonged visual strain, and nourishes the eyes. When combined with angelica, one nourishes and the other moistens, enhancing the effect of nourishing blood and improving eyesight, addressing both the root cause and the symptoms. Buddleja officinalis, sweet and slightly cold, clears liver heat and nourishes liver blood. It can help clear the deficiency heat caused by staying up late and excessive eye use in teenagers, while also preventing the warming properties of angelica and chuanxiong from exacerbating the heat, and also treats excessive tearing and photophobia. Honeysuckle, sweet and cold, clears heat and detoxifies, and promotes the elimination of heat. It inhibits inflammation while balancing the warming properties of angelica and chuanxiong, preventing dryness from damaging the eyes. Chuanxiong, pungent, warm, and aromatic, ascends to the head and eyes, invigorates blood and qi, and can assist danshen in enhancing its ability to remove blood stasis and unblock collaterals, as well as assist angelica in enhancing its blood-nourishing and blood-activating effects.

[0019] With bilberry and astragalus as adjuvants, bilberry can promote the regeneration of rhodopsin, quickly relieve eye fatigue, assist the principal drug in eliminating symptoms, and clear free radicals produced by inflammation; astragalus is sweet and slightly warm, replenishes qi and raises yang, and when qi is strong, blood flows smoothly, which helps salvia miltiorrhiza, angelica sinensis and chuanxiong to promote the circulation of qi and blood, while also counteracting the cold nature of honeysuckle and buddleja officinalis.

[0020] Licorice is used as the guiding herb to harmonize the other herbs, relieve pain, and alleviate eye muscle spasms. At the same time, it balances the warming properties of Angelica sinensis and Ligusticum chuanxiong with the cooling properties of Lonicera japonica and Buddleja officinalis, thus having an anti-inflammatory effect. It works synergistically with the whole formula to make the whole formula mild in nature, without any warming or drying or cooling bias, making it suitable for the constitution of teenagers.

[0021] The formula is based on promoting blood circulation, nourishing blood, clearing the meridians, and improving eyesight. It is supplemented with clearing heat and detoxifying, anti-inflammatory and swelling-reducing to treat the symptoms, nourishing the liver and kidneys and nourishing the retina to strengthen the root cause, and guiding the medicine upward and replenishing qi to remove toxins to facilitate its function. It forms a complete treatment principle of "nourishing, clearing, clearing and nourishing", which can take into account both the symptoms and the root cause, so as to prevent and treat myopia caused by prolonged screen time and its complications such as eye inflammation, redness, swelling and burning. It is especially suitable for teenagers who use their eyes for a long time and have insufficient qi and blood.

[0022] In some embodiments, the poloxamer is poloxamer-407, and the modified chitosan has a structure as shown in formula (I): (I).

[0023] In some embodiments, the matrix of the hydrogel layer further includes 0.005-0.02 parts of a preservative; optionally, the preservative is selected from one or more of potassium sorbate, methylparaben, and ethylparaben.

[0024] In some embodiments, the weight ratio of the traditional Chinese medicine extract to the matrix in the hydrogel layer is 1:(8-20).

[0025] In some embodiments, the herbal hydrogel eye patch for preventing and treating myopia in adolescents further includes a backing layer and a protective layer, the backing layer and the protective layer being located on opposite sides of the hydrogel layer loaded with herbal extracts. In use, the protective layer is peeled off, and the hydrogel layer loaded with herbal extracts is applied to the eye. The backing layer can be a non-woven fabric, and the protective layer is selected from any one of polyester film, polypropylene film, polyethylene film, siliconeized polyester film, and siliconeized paper. Other materials that can serve as hydrogel layer carriers in the art can be used as backing layers in this invention, and other materials that can serve as hydrogel layer covers in the art can be used as protective layers in this invention.

[0026] This invention also provides a method for preparing a traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents, comprising the following steps: (1) Dissolve poloxamer and modified chitosan in water to obtain solution A; dissolve sodium glycerophosphate, sodium phytate and sodium pyrrolidone carboxylate in water to obtain solution B; (2) Mix sphingomyelin with solution A, add the Chinese herbal extract, mix well, then add solution B and mix well to obtain a drug-loaded gel; (3) The drug-loaded gel is evenly coated on the backing layer and left to stand for aging to obtain the Chinese herbal hydrogel eye patch.

[0027] Preferably, in step (1), solution A is obtained by the following method: at 2-8°C, poloxamer and modified chitosan are dissolved in water and allowed to stand for 8-12 hours. Then, citrate-sodium citrate buffer solution pre-cooled to the same temperature is added under stirring, and the pH value is adjusted to 4.8-5.2 to obtain transparent solution A.

[0028] Preferably, in step (1), the concentration of poloxamer in solution A is 20wt%-25wt%, and the volume ratio of solution A to solution B is 1:(0.1-0.2).

[0029] Preferably, step (2) specifically includes: mixing sphingomyelin with solution A at a temperature of 2-8°C, stirring for 20-40 minutes, adding the traditional Chinese medicine extract, continuing to stir for 20-40 minutes, then adding solution B at a temperature of 20-25°C and a speed of 50-150 rpm, and continuing to stir and react for 30-50 minutes to obtain a drug-loaded gel. In some preferred embodiments, a peristaltic pump can be used to add solution B slowly.

[0030] Preferably, in step (2), the herbal extract is prepared by the following method: take Danshen, Danggui, Gouqizi, Mimenghua, Chuanxiong, Jinyinhua, Lanju, Huangqi, and Gancao, mix them evenly, pulverize them, add 8-12 times the amount of 60%-75% ethanol aqueous solution, heat and reflux to extract 2-3 times, each time for 1.5-2 hours, combine the extracts, filter, concentrate and dry to obtain the extract.

[0031] The above-described solution of the present invention has at least the following beneficial effects: (1) The herbal hydrogel eye patch for preventing and treating myopia in adolescents according to the present invention comprises at least a hydrogel layer loaded with herbal extracts; the herbal extracts include the following raw materials: Salvia miltiorrhiza, Angelica sinensis, Lycium barbarum, Buddleja officinalis, Ligusticum chuanxiong, Lonicera japonica, Vaccaria segetalis, Astragalus membranaceus, and Glycyrrhiza uralensis; the matrix of the hydrogel layer comprises the following raw materials in parts by weight: 20-25 parts poloxamer, 2.0-4.0 parts sphingomyelin, 1.5-2.0 parts sodium glycerophosphate, 0.5-0.8 parts sodium phytate, 1.0-2.0 parts modified chitosan, and 0.5-1.0 parts sodium pyrrolidone carboxylate. The herbal hydrogel eye patch for preventing and treating myopia in adolescents according to the present invention has excellent drug loading performance, good transdermal absorption, and good myopia prevention and treatment effect.

[0032] (2) The herbal hydrogel eye patch for preventing and treating myopia in adolescents described in this invention has high stability, large drug loading capacity and good transdermal effect through the synergistic effect of poloxamer, modified chitosan and sphingomyelin.

[0033] The components of the traditional Chinese medicine extracts are complex. For example, the principal herbs in the traditional Chinese medicine formula, Danshen and Danggui, contain hydrophobic components such as tanshinone, while their components, such as tanshinone and Danggui polysaccharides, have good hydrophilicity. Poloxamer is a copolymer obtained by polymerizing polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO). Hydrophilic drugs in the traditional Chinese medicine extracts can be uniformly dispersed in poloxamer solutions, and hydrophobic drugs can be encapsulated in its hydrophobic core. Although poloxamer can encapsulate hydrophobic components by forming micelles, its drug loading capacity is limited, and its solubilizing ability and encapsulation stability for hydrophobic drugs are insufficient.

[0034] Sphingomyelin is an amphoteric phospholipid composed of sphingosine, fatty acids, and phosphocholine. It can self-assemble into a liquid crystal phase with a lipid bilayer structure. This ordered structure provides ample hydrophobic regions between the layers, improving the drug-carrying capacity of hydrophobic drugs. Simultaneously, its hydrophilic regions can accommodate a large number of water molecules, stabilizing hydrophilic drugs. Furthermore, the chemical structure of sphingomyelin is highly compatible with the stratum corneum of the skin, enhancing transdermal drug absorption efficiency. However, when mixed with high-concentration poloxamer solutions, poloxamer tends to over-insert into the sphingomyelin bilayer, disrupting its structural integrity and leading to decreased drug-carrying capacity, water retention capacity, and transdermal absorption. The modified chitosan, however, prevents high-concentration poloxamer from over-inserting into the sphingomyelin bilayer, competing with poloxamer for insertion sites and protecting the integrity of the sphingomyelin layered structure.

[0035] After the addition of sodium glycerophosphate and sodium phytate, modified chitosan can construct a multi-linked network, which can effectively constrain the free migration of poloxamer micelles, prevent the destruction of sphingomyelin structure, improve the stability of hydrogel system, and enhance the mechanical strength of gel matrix. When isopropyl groups are introduced into the side chains of the modified chitosan, the stability of hydrogel system can be further improved.

[0036] (3) The herbal hydrogel eye patch for preventing and treating myopia in adolescents of the present invention contains sodium pyrrolidone carboxylate in the matrix of the hydrogel layer, which has a moisturizing function and works synergistically with sphingomyelin to promote transdermal absorption of the drug and maintain the stability of the hydrogel system. Detailed Implementation

[0037] Unless otherwise specified in the embodiments of this invention, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available products; different manufacturers and models of raw materials do not affect the implementation of the technical solution or the achievement of the technical effect of this invention.

[0038] In the following embodiments, the raw materials used are all prepared using existing technologies or are commercially available products. The citric acid-sodium citrate buffer solution is a conventional component of existing technologies, capable of providing a relatively stable acid-base environment.

[0039] Modified chitosan has the structure shown in formula (I): (I).

[0040] The modified chitosan shown in formula (I) is a known substance in the prior art, which can be directly purchased or prepared using existing technologies. For example, it can be prepared by reacting acetone with the amino groups of chitosan in a reducing agent. Example 1

[0041] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this embodiment includes a hydrogel layer loaded with herbal extracts; in the hydrogel layer, the weight ratio of the herbal extracts to the matrix is ​​1:12. The herbal extract includes the following raw materials: Salvia miltiorrhiza 80 parts, Angelica sinensis 65 parts, Lycium barbarum 55 parts, Buddleja officinalis 50 parts, Ligusticum chuanxiong 35 parts, Lonicera japonica 40 parts, Vaccaria segetalis 35 parts, Astragalus membranaceus 25 parts, Glycyrrhiza uralensis 8 parts.

[0042] The matrix of the hydrogel layer comprises the following raw materials in parts by weight: The mixture contains 20 parts of poloxamer-407, 2.0 parts of sphingomyelin, 1.8 parts of sodium glycerophosphate, 0.6 parts of sodium phytate, 2.0 parts of modified chitosan, 1.0 part of sodium pyrrolidone carboxylate, and 0.01 parts of preservative; wherein the modified chitosan has the structure shown in formula (I); the preservative is selected from one or more of potassium sorbate, methylparaben, and ethylparaben, and in this embodiment, the preservative is potassium sorbate.

[0043] In this embodiment, the preparation method of the traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents specifically includes the following steps: (1) At 4°C, poloxamer-407 and modified chitosan were dissolved in water and allowed to stand for 12 hours. Then, citrate-sodium citrate buffer solution pre-cooled to the same temperature was added with stirring to adjust the pH to 5.2, resulting in a transparent solution A. The concentration of poloxamer-407 in solution A was 20 wt%, and the concentration of modified chitosan in solution A was 2.0 wt%. Sodium glycerophosphate, sodium phytate, and sodium pyrrolidone carboxylate were dissolved in water to obtain solution B. The volume ratio of solution A to solution B was 1:0.1. (2) At a temperature of 4°C, sphingomyelin was mixed with solution A and stirred for 40 min. The Chinese herbal extract was added and stirred for another 30 min. Then, at a temperature of 25°C and a speed of 50 rpm, solution B was slowly added and stirred for another 30 min while maintaining the same stirring speed to obtain the drug-loaded gel. The herbal extract is prepared by the following method: take Salvia miltiorrhiza, Angelica sinensis, Lycium barbarum, Buddleja officinalis, Ligusticum chuanxiong, Lonicera japonica, Vaccaria segetalis, Astragalus membranaceus, and Glycyrrhiza uralensis, mix them evenly, pulverize them, add 8 times the amount of 75% ethanol aqueous solution, heat and reflux to extract twice, each time for 2 hours, combine the extracts, filter, distill the filtrate under reduced pressure to recover the ethanol until there is no alcohol taste, continue to concentrate, and dry to obtain the extract; (3) The drug-loaded gel is evenly coated on the backing layer and aged at 25°C for 5 hours to obtain the Chinese herbal hydrogel eye patch. The backing layer can be a non-woven fabric. Example 2

[0044] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this embodiment includes at least a hydrogel layer loaded with herbal extracts; in the hydrogel layer, the weight ratio of the herbal extracts to the matrix is ​​1:12. The herbal extract includes the following raw materials: Salvia miltiorrhiza 90 parts, Angelica sinensis 55 parts, Lycium barbarum 50 parts, Buddleja officinalis 55 parts, Ligusticum chuanxiong 40 parts, Lonicera japonica 35 parts, Vaccaria segetalis 25 parts, Astragalus membranaceus 20 parts, Glycyrrhiza uralensis 10 parts.

[0045] The matrix of the hydrogel layer comprises the following raw materials in parts by weight: The mixture contains 25 parts of poloxamer-407, 4.0 parts of sphingomyelin, 2.0 parts of sodium glycerophosphate, 0.3 parts of sodium phytate, 1.0 part of modified chitosan, 1.0 part of sodium pyrrolidone carboxylate, and 0.01 parts of preservative; wherein the modified chitosan has the structure shown in formula (I); the preservative is selected from one or more of potassium sorbate, methylparaben, and ethylparaben, and in this embodiment, the preservative is potassium sorbate.

[0046] In this embodiment, the preparation method of the traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents specifically includes the following steps: (1) At 6°C, poloxamer-407 and modified chitosan were dissolved in water and allowed to stand for 10 h. Then, citrate-sodium citrate buffer solution pre-cooled to the same temperature was added with stirring to adjust the pH to 4.8, resulting in a transparent solution A. The concentration of poloxamer-407 in solution A was 25 wt%, and the concentration of modified chitosan in solution A was 1.0 wt%. Sodium glycerophosphate, sodium phytate, and sodium pyrrolidone carboxylate were dissolved in water to obtain solution B. The volume ratio of solution A to solution B was 1:0.1. (2) At a temperature of 6°C, sphingomyelin was mixed with solution A and stirred for 20 min. Then, the Chinese herbal extract was added and stirred for another 40 min. Then, at a temperature of 22°C and a speed of 100 rpm, solution B was slowly added and stirred for another 50 min at the same stirring speed to obtain the drug-loaded gel. The herbal extract is prepared by the following method: take Salvia miltiorrhiza, Angelica sinensis, Lycium barbarum, Buddleja officinalis, Ligusticum chuanxiong, Lonicera japonica, Vaccaria segetalis, Astragalus membranaceus, and Glycyrrhiza uralensis, mix them evenly, pulverize them, add 10 times the amount of 70% ethanol aqueous solution, heat and reflux to extract 3 times, 1.5 hours each time, combine the extracts, filter, distill the filtrate under reduced pressure to recover the ethanol until there is no alcohol taste, continue to concentrate, and dry to obtain the extract; (3) The drug-loaded gel is evenly coated on the backing layer and aged at 25°C for 8 hours to obtain the Chinese herbal hydrogel eye patch. The backing layer can be a non-woven fabric. Example 3

[0047] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this embodiment includes at least a hydrogel layer loaded with herbal extracts; in the hydrogel layer, the weight ratio of the herbal extracts to the matrix is ​​1:10. The herbal extract includes the following raw materials: Salvia miltiorrhiza 85 parts, Angelica sinensis 60 parts, Lycium barbarum 60 parts, Buddleja officinalis 45 parts, Ligusticum chuanxiong 45 parts, Lonicera japonica 35 parts, Vaccaria segetalis 30 parts, Astragalus membranaceus 30 parts, Glycyrrhiza uralensis 12 parts.

[0048] The matrix of the hydrogel layer comprises the following raw materials in parts by weight: The mixture contains 22 parts poloxamer-407, 3.0 parts sphingomyelin, 1.8 parts sodium glycerophosphate, 0.8 parts sodium phytate, 1.8 parts modified chitosan, 1.0 parts sodium pyrrolidone carboxylate, and 0.01 parts preservative; wherein the modified chitosan has the structure shown in formula (I); the preservative is selected from one or more of potassium sorbate, methylparaben, and ethylparaben. In this embodiment, the preservative is a mixture of methylparaben and ethylparaben in a weight ratio of 1:1.

[0049] In this embodiment, the preparation method of the traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents specifically includes the following steps: (1) At 2°C, poloxamer-407 and modified chitosan were dissolved in water and allowed to stand for 8 hours. Then, citrate-sodium citrate buffer solution pre-cooled to the same temperature was added with stirring to adjust the pH to 5.0, resulting in a transparent solution A. The concentration of poloxamer-407 in solution A was 22 wt%, and the concentration of modified chitosan in solution A was 1.8 wt%. Sodium glycerophosphate, sodium phytate, and sodium pyrrolidone carboxylate were dissolved in water to obtain solution B. The volume ratio of solution A to solution B was 1:0.2. (2) At a temperature of 2°C, sphingomyelin was mixed with solution A and stirred for 30 min. The Chinese herbal extract was added and stirred for another 20 min. Then, at a temperature of 20°C and a speed of 150 rpm, solution B was slowly added and stirred for another 40 min at the same stirring speed to obtain the drug-loaded gel. The herbal extract is prepared by the following method: take Salvia miltiorrhiza, Angelica sinensis, Lycium barbarum, Buddleja officinalis, Ligusticum chuanxiong, Lonicera japonica, Vaccaria segetalis, Astragalus membranaceus, and Glycyrrhiza uralensis, mix them evenly, pulverize them, add 12 times the amount of 60% ethanol aqueous solution, heat and reflux to extract twice, each time for 2 hours, combine the extracts, filter, distill the filtrate under reduced pressure to recover the ethanol until there is no alcohol taste, continue to concentrate, and dry to obtain the extract; (3) The drug-loaded gel is evenly coated on the backing layer and aged at 25°C for 4 hours to obtain the Chinese herbal hydrogel eye patch. The backing layer can be a non-woven fabric. Example 4

[0050] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this embodiment includes at least a hydrogel layer loaded with herbal extracts; in the hydrogel layer, the weight ratio of the herbal extracts to the matrix is ​​1:10. The herbal extract includes the following raw materials: Salvia miltiorrhiza 88 parts, Angelica sinensis 62 parts, Lycium barbarum 54 parts, Buddleja officinalis 50 parts, Ligusticum chuanxiong 38 parts, Lonicera japonica 42 parts, Vaccaria segetalis 32 parts, Astragalus membranaceus 28 parts, Glycyrrhiza uralensis 10 parts.

[0051] The matrix of the hydrogel layer comprises the following raw materials in parts by weight: The mixture contains 22 parts poloxamer-407, 3.0 parts sphingomyelin, 1.8 parts sodium glycerophosphate, 0.6 parts sodium phytate, 1.8 parts modified chitosan, 1.0 parts sodium pyrrolidone carboxylate, and 0.02 parts preservative; wherein the modified chitosan has the structure shown in formula (I); the preservative is selected from one or more of potassium sorbate, methylparaben, and ethylparaben. In this embodiment, the preservative is a mixture of methylparaben and ethylparaben in a weight ratio of 1:1.

[0052] In this embodiment, the preparation method of the traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents specifically includes the following steps: (1) At 4°C, poloxamer-407 and modified chitosan were dissolved in water and allowed to stand for 10 h. Then, with stirring, citrate-sodium citrate buffer solution pre-cooled to the same temperature was added to adjust the pH to 5.0 to obtain a transparent solution A. The concentration of poloxamer-407 in solution A was 22 wt%, and the concentration of modified chitosan in solution A was 1.8 wt%. Sodium glycerophosphate, sodium phytate, and sodium pyrrolidone carboxylate were dissolved in water to obtain solution B. The volume ratio of solution A to solution B was 1:0.1. (2) At a temperature of 4°C, sphingomyelin was mixed with solution A and stirred for 30 min. The Chinese herbal extract was added and stirred for another 30 min. Then, at a temperature of 20°C and a speed of 100 rpm, solution B was slowly added and stirred for another 40 min at the same stirring speed to obtain the drug-loaded gel. The herbal extract is prepared by the following method: take Salvia miltiorrhiza, Angelica sinensis, Lycium barbarum, Buddleja officinalis, Ligusticum chuanxiong, Lonicera japonica, Vaccaria segetalis, Astragalus membranaceus, and Glycyrrhiza uralensis, mix them evenly, pulverize them, add 10 times the amount of 70% ethanol aqueous solution, heat and reflux to extract twice, each time for 2 hours, combine the extracts, filter, distill the filtrate under reduced pressure to recover the ethanol until there is no alcohol taste, continue to concentrate, and dry to obtain the extract; (3) The drug-loaded gel is evenly coated on the backing layer and aged at 25°C for 5 hours to obtain the Chinese herbal hydrogel eye patch. The backing layer can be a non-woven fabric. Comparative Example 1

[0053] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this comparative example is the same as that in Example 4, except that the modified chitosan shown in Formula (I) is replaced with unmodified chitosan in the matrix of the hydrogel layer. Comparative Example 2

[0054] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this comparative example is the same as that in Example 4, except that the modified chitosan shown in Formula (I) is replaced with carboxymethyl chitosan in the matrix of the hydrogel layer. Comparative Example 3

[0055] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this comparative example is the same as that in Example 4, except that no modified chitosan is added to the matrix of the hydrogel layer. Comparative Example 4

[0056] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this comparative example is the same as that in Example 4, except that sphingomyelin is not added to the matrix of the hydrogel layer. Comparative Example 5

[0057] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this comparative example is the same as that in Example 4, except that sphingomyelin is replaced with lecithin in the matrix of the hydrogel layer. Comparative Example 6

[0058] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this comparative example is the same as that in Example 4, except that sodium phytate is not added to the matrix of the hydrogel layer. Comparative Example 7

[0059] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this comparative example is the same as that in Example 4, except that sodium glycerophosphate is not added to the matrix of the hydrogel layer. Comparative Example 8

[0060] The herbal hydrogel eye patch for preventing and treating myopia in adolescents in this comparative example is the same as that in Example 4, except that sodium pyrrolidone carboxylate was not added to the matrix of the hydrogel layer. Comparative Example 9

[0061] This comparative example of a herbal hydrogel eye patch for preventing and treating myopia in adolescents is the same as that in Example 4, except that it does not include the herbal extract. That is, the hydrogel layer does not carry the herbal extract and serves as a blank matrix. Effect Experiment Example

[0062] To verify the technical efficacy of the herbal hydrogel eye patch for preventing and treating myopia in adolescents as described in this invention, the following experiments were conducted: 1. Drug loading performance test Take the herbal hydrogel eye patches for preventing and treating myopia in adolescents from Examples 1-4 and Comparative Examples 1-9, place them in a drying oven and dry them to constant weight. Cut the dried hydrogel eye patches into small pieces, place them in an Erlenmeyer flask, add 80% ethanol aqueous solution, and extract by ultrasonication for 30 minutes. Repeat twice, combine the extracts, detect the content of tanshinone IIA, and calculate the drug loading (mg / g of dried hydrogel eye patch; the coating amount of the hydrogel eye patch before drying was 500g / m²).

[0063] The content of tanshinone IIA was determined according to high performance liquid chromatography (General Chapter 0512 of the Chinese Pharmacopoeia 2020 edition), the same below.

[0064] 2. Transdermal absorption performance test Kunming mice were euthanized by cervical dislocation. Abdominal skin was quickly cut off, and after hair removal, subcutaneous fat, fascia and adhesions were removed to ensure that the skin was intact and undamaged. The skin was repeatedly rinsed with physiological saline and the integrity of the skin was tested. The mouse skin was fixed between the supply and receiving pools of the Franz diffusion cell, with the stratum corneum facing upwards (towards the supply pool) and the dermis facing downwards (towards the receiving pool). The two pools were secured with clamps to ensure a good seal and no leakage. The effective diffusion area (A, cm²) and the volume of the receiving pool (V, mL) were recorded. After filling the receiving pool with receiving liquid, air bubbles were removed. The herbal hydrogel eye patches for preventing myopia in adolescents from Examples 1-4 and Comparative Examples 1-9 were cut to sizes matching the area of ​​the diffusion pool and tightly applied to the surface of the stratum corneum of the mouse skin, removing air bubbles. The constant temperature water bath and magnetic stirrer were turned on. The water bath temperature was set to 34±0.5℃ and the magnetic stirring speed was set to 300rpm. 1mL of receiving liquid was taken out at 0.5, 1, 6, 12, and 24h, and an equal amount of fresh receiving medium at the same time was added to the receiving pool. The collected receiving liquid was filtered through a 0.22 μm microporous membrane and the concentration of tanshinone IIA was measured. The cumulative permeation per unit area was calculated. The cumulative infiltration per unit area can be calculated using the following formula: ; in, For the first Drug concentrations measured at various time points For the first The drug concentration measured at each time point, in μg / mL; The volume of the receiving cell is in mL; For each sampling volume, in this experiment, 1 mL; The effective diffusion area, or effective penetration area, is expressed in cm². The unit is μg / cm²; 3. Water retention performance test Take the herbal hydrogel eye patches for preventing and treating myopia in adolescents obtained in Examples 1-4 and Comparative Examples 1-9, weigh them, and record the weight as W1. Then place them in an environment of 25℃±2℃ and RH65%±5% for 3 months, weigh them again, and record the weight as W2. Calculate the water retention rate using the following formula: W2 / W1×100%. Conduct three parallel experiments and take the average value.

[0065] 4. Usage effect test One hundred adolescents aged 8-18 years with myopia (myopia degree ≤ -3.00D) were randomly divided into two groups. One group received treatment with the herbal hydrogel eye patch for preventing and treating adolescent myopia prepared in Example 4, while the other group received a control using the blank matrix in Example 9. During the observation period, the patches were applied to the eyes twice daily, morning and evening, for 20 minutes each time. One course of treatment lasted 8 weeks. Changes in discomfort symptoms and visual acuity indicators (using a standard logarithmic visual acuity chart) were observed before treatment and after one course of treatment.

[0066] The treatment effect shall be determined according to the following criteria: If the subjective visual discomfort disappears, such as blurred vision, eye soreness, redness, burning, etc.; or if the uncorrected distance visual acuity improves by 0.1 or more (excluding 0.1, the sum of both eyes), it is considered valid; if the above standards are not met, it is considered invalid.

[0067] The results of the drug loading performance test, transdermal absorption performance test, and drug stability test are shown in Table 1, and the results of the efficacy test are shown in Table 2. Table 1

[0068] Table 2

[0069] Based on the above experimental results, it can be seen that the herbal hydrogel eye patch for preventing and treating myopia in adolescents described in this invention can improve the clinical symptoms of myopia patients and effectively prevent and treat myopia in adolescents.

[0070] Based on the results of Example 4 and Comparative Examples 1-3, it can be seen that the modified chitosan shown in Formula (I) has a significant effect on the drug loading capacity, transdermal absorption capacity, and water retention capacity of the hydrogel eye patch. This may be because the introduction of isopropyl makes chitosan amphiphilic, which is beneficial to its interaction with sphingomyelin and effectively prevents excessive insertion of poloxamer. Comparative Example 1 used chitosan instead of the modified chitosan shown in Formula (I), but because it was difficult to form a stable protection on the surface of sphingomyelin, its structure was easily damaged, and the drug loading capacity, transdermal absorption rate, and water retention capacity were significantly reduced. Comparative Example 2 used Carboxymethyl chitosan replaced the modified chitosan shown in formula (I). Carboxymethyl chitosan is a hydrophilic modified chitosan. Compared with Comparative Example 1, its drug loading and transdermal absorption rate decreased, but its water retention capacity was slightly improved. This indicates that the protective effect of hydrophilic modified chitosan on sphingomyelin was further weakened, but it had a certain beneficial effect on water retention capacity. Comparative Example 3 did not add the modified chitosan shown in formula (I). Compared with Comparative Examples 1 and 2, its drug loading, transdermal absorption rate and water retention capacity were significantly reduced. This indicates that the cross-linking of the linear polysaccharide chains of chitosan has a significant impact on the overall performance of the hydrogel.

[0071] Based on the results of Example 4 and Comparative Examples 4-5, it can be seen that the lamellar liquid crystal phase structure of sphingomyelin has a significant impact on the drug loading performance, transdermal absorption performance, and water retention performance of hydrogel eye patches. This may be because although lecithin can also form a lamellar liquid crystal phase in water, it is rich in unsaturated fatty acid chains. Under body temperature and storage conditions, the liquid crystal phase is prone to flow and structural rearrangement, resulting in unstable liquid crystal phase structure. Furthermore, the lecithin liquid crystal phase has poor compactness and relatively loose lipid molecule arrangement, making it easier for poloxamer to insert into it and destroy its lamellar structure. Therefore, its interlayer drug loading capacity is affected, the drug loading of tanshinone IIA decreases, and the transdermal absorption efficiency is also relatively low.

[0072] Based on the results of Example 4 and Comparative Examples 6-8, it is evident that the absence of sodium phytate or sodium glycerophosphate negatively impacts the drug loading, transdermal absorption, and water retention properties of the hydrogel eye patch. This may be because sodium phytate has multiple cross-linking sites, resulting in a high-density but poorly uniform cross-linking network. Sodium glycerophosphate, on the other hand, forms a looser cross-linking network but cannot effectively constrain poloxamer. The combined use of both produces the hydrogel with the best overall performance. The absence of sodium pyrrolidone carboxylate significantly affects the transdermal absorption and water retention properties of the hydrogel eye patch.

[0073] Based on the results of Example 4 and Comparative Example 9, it can be seen that, compared with the blank control group, Example 4 was effective in 96% of patients and could significantly improve the related symptoms of myopia in adolescents.

[0074] As is known from common technical knowledge, this invention can be implemented through other embodiments that do not depart from its spirit or essential characteristics. Therefore, the disclosed embodiments described above are merely illustrative in all respects and are not the only ones. All modifications within the scope of this invention or its equivalents are encompassed by this invention.

Claims

1. A traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents, characterized in that, It should include at least a hydrogel layer loaded with Chinese herbal extracts; The herbal extract includes the following raw materials: Salvia miltiorrhiza, Angelica sinensis, Lycium barbarum, Buddleja officinalis, Ligusticum chuanxiong, Lonicera japonica, Vaccaria segetalis, Astragalus membranaceus, Glycyrrhiza uralensis; The matrix of the hydrogel layer comprises the following raw materials in parts by weight: Poloxamer 20-25 parts, sphingomyelin 2.0-4.0 parts, sodium glycerophosphate 1.5-2.0 parts, sodium phytate 0.5-0.8 parts, modified chitosan 1.0-2.0 parts, sodium pyrrolidone carboxylate 0.5-1.0 parts.

2. The herbal hydrogel eye patch for preventing and treating myopia in adolescents according to claim 1, characterized in that, The herbal extract comprises the following raw materials in parts by weight: Salvia miltiorrhiza 80-90 parts, Angelica sinensis 55-65 parts, Lycium barbarum 50-60 parts, Buddleja officinalis 45-55 parts, Ligusticum chuanxiong 35-45 parts, Lonicera japonica 35-45 parts, Vaccaria segetalis 25-35 parts, Astragalus membranaceus 20-30 parts, Glycyrrhiza uralensis 8-12 parts.

3. The herbal hydrogel eye patch for preventing and treating myopia in adolescents according to claim 1, characterized in that, The poloxamer in question is poloxamer-407; The modified chitosan has a structure as shown in formula (I): （Ⅰ）。 4. The herbal hydrogel eye patch for preventing and treating myopia in adolescents according to claim 1, characterized in that, The matrix of the hydrogel layer also includes 0.005-0.02 parts of preservative; Optionally, the preservative is selected from one or more of potassium sorbate, methylparaben, and ethylparaben.

5. The herbal hydrogel eye patch for preventing and treating myopia in adolescents according to claim 1, characterized in that, In the hydrogel layer, the weight ratio of the traditional Chinese medicine extract to the matrix is ​​1:(8-20).

6. A method for preparing a traditional Chinese medicine hydrogel eye patch for preventing and treating myopia in adolescents as described in any one of claims 1-5, characterized in that, Includes the following steps: (1) Dissolve poloxamer and modified chitosan in water to obtain solution A; dissolve sodium glycerophosphate, sodium phytate and sodium pyrrolidone carboxylate in water to obtain solution B; (2) Mix sphingomyelin with solution A, add the Chinese herbal extract, mix well, then add solution B and mix well to obtain a drug-loaded gel; (3) The drug-loaded gel is evenly coated on the backing layer and left to stand for aging to obtain the Chinese herbal hydrogel eye patch.

7. The preparation method of the herbal hydrogel eye patch for preventing and treating myopia in adolescents according to claim 6, characterized in that, In step (1), solution A is obtained by the following method: at 2-8℃, poloxamer and modified chitosan are dissolved in water and allowed to stand for 8-12 hours. Then, citrate-sodium citrate buffer solution pre-cooled to the same temperature is added under stirring, and the pH value is adjusted to 4.8-5.2 to obtain transparent solution A.

8. The preparation method of the herbal hydrogel eye patch for preventing and treating myopia in adolescents according to claim 6, characterized in that, In step (1), the concentration of poloxamer in solution A is 20wt%-25wt%, and the volume ratio of solution A to solution B is 1:(0.1-0.2).

9. The preparation method of the herbal hydrogel eye patch for preventing and treating myopia in adolescents according to claim 6, characterized in that, Step (2) specifically includes: mixing sphingomyelin with solution A at a temperature of 2-8℃, stirring for 20-40 min, adding the Chinese herbal extract, continuing to stir for 20-40 min, then adding solution B at a temperature of 20-25℃ and a speed of 50-150 rpm, and continuing to stir and react for 30-50 min to obtain the drug-loaded gel.

10. The preparation method of the herbal hydrogel eye patch for preventing and treating myopia in adolescents according to claim 6, characterized in that, In step (2), the herbal extract is prepared by the following method: take Danshen, Danggui, Gouqizi, Mimenghua, Chuanxiong, Jinyinhua, Lanju, Huangqi, and Gancao, mix them evenly, pulverize them, add 8-12 times the amount of 60%-75% ethanol aqueous solution, heat and reflux to extract 2-3 times, each time for 1.5-2 hours, combine the extracts, filter, concentrate and dry to obtain the extract.

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