Pure traditional Chinese medicine eye drops prepared by ancient method for treating xerophthalmia and preparation method of pure traditional Chinese medicine eye drops

Abstract

The invention belongs to the technical field of eye drops, and particularly relates to pure traditional Chinese medicine eye drops prepared by an ancient method for treating xerophthalmia and a preparation method. The pure traditional Chinese medicine eye drops for treating xerophthalmia are characterized by being prepared from the following traditional Chinese medicines in parts by weight: 18-28 parts of radix astragali, 12-18 parts of radix glehniae, 7-11 parts of rhizoma cyperi, 6-9 parts of perilla leaves, 10-14 parts of radix puerariae, 7-11 parts of herba schizonepetae and 6-9 parts of Chinese dates. The astragalus membranaceus is honey-fried astragalus membranaceus, and the weight ratio of honey to astragalus membranaceus is 1: (4-6); the schizonepeta is charred schizonepeta, and the charring temperature is 170-190 DEG C; the rhizoma cyperi is vinegar-processed rhizoma cyperi, and the soaking time of the vinegar is 5-7 hours. The irritation of the medicinal materials is reduced through an ancient processing technology, water-soluble and fat-soluble components are synchronously enriched in combination with a modern deep eutectic solvent extraction technology, the safety is improved by adopting a freeze-drying technology without preservatives, and a better choice is provided for patients with xerophthalmia.

Description

Technical Field

[0001] The invention belongs to the technical field of eye drops, and particularly relates to an eye drop prepared by a traditional Chinese medicine method for treating dry eyes and a preparation method thereof. Background Art

[0002] Dry eye syndrome is a common eye disease characterized by dryness, fatigue, and a foreign body sensation. In severe cases, it can lead to corneal damage and even vision loss. With increasing screen time, worsening air pollution, and an aging population, the number of dry eye patients worldwide is increasing annually and is expected to exceed 1 billion by 2030. Currently, Western medicine treatments primarily focus on artificial tears such as sodium hyaluronate eye drops and anti-inflammatory drugs such as cyclosporine. However, long-term use can cause corneal toxicity or drug resistance and does not address the underlying cause.

[0003] Traditional Chinese medicine has unique advantages in treating dry eye. Traditional Chinese medicine believes that dry eye is related to "deficiency of both qi and yin" and "liver depression and wind-heat." Through a combination of Qi-tonifying and Yin-nourishing, wind-clearing and meridian-dredging formulas, tear secretion and tear film stability can be improved simultaneously. However, existing traditional Chinese medicine eye drops have several shortcomings: First, they are highly irritating. Some herbs, such as raw schizonepeta and raw cyperus, contain volatile components or acidic substances, which can easily cause ocular surface burning and conjunctival congestion when used directly. Second, their efficacy is insufficient. Traditional decoction processes can only extract water-soluble components, while the extraction rate of fat-soluble active ingredients is low, resulting in a single efficacy.

[0004] Furthermore, commercially available eye drops often rely on chemical preservatives such as benzalkonium chloride to extend their shelf life, which can damage corneal epithelial cells with long-term use. Therefore, there is an urgent need to develop pure Chinese herbal eye drops that retain the therapeutic advantages of traditional Chinese medicine while addressing the issues of high irritation and incomplete ingredient extraction. Summary of the Invention

[0005] The invention provides a pure traditional Chinese medicine eye drop for treating dry eye. The eye drop is prepared from the following traditional Chinese medicines in the following weight proportions: 18-28 parts of astragalus, 12-18 parts of northern adenophora, 7-11 parts of cyperus, 6-9 parts of perilla leaves, 10-14 parts of kudzu root, 7-11 parts of schizonepeta, and 6-9 parts of jujube; the astragalus is honey-roasted astragalus, and the weight ratio of honey to astragalus is 1:4-6; the schizonepeta is charcoal-processed, and the carbonization temperature is 170-190°C; and the cyperus is vinegar-processed, and the soaking time in rice vinegar is 5-7 hours.

[0006] In some embodiments, the drug is prepared from the following Chinese medicines in the following weight ratios: 20-25 parts of Astragalus, 14-16 parts of Glehnia littoralis, 8-10 parts of Cyperus rotundus, 7-8 parts of Perilla frutescens leaves, 11-13 parts of Pueraria root, 8-10 parts of Schizonepeta tenuifolia, and 7-8 parts of jujube.

[0007] In some embodiments, the weight ratio of honey to astragalus in the honey-roasted astragalus is 1:5, the carbonization temperature of the charcoal-processed schizonepeta tenuifolia is 180° C., and the soaking time of the vinegar-processed cyperus rotundus in rice vinegar is 6 hours.

[0008] The present invention also provides a method for preparing pure Chinese herbal eye drops for treating dry eye, comprising the following steps:

[0009] (1) Mix astragalus and honey in appropriate proportions, stir-fry over low heat until the surface turns dark yellow, and obtain honey-roasted astragalus; stir-fry schizonepeta at 170-190°C until the surface turns black, and obtain charcoal-roasted schizonepeta; soak cyperus rotundus in rice vinegar for 5-7 hours, stir-fry until dry, and obtain vinegar-roasted cyperus rotundus;

[0010] (2) Water extraction layer: Add honey-roasted Astragalus, Glehnia littoralis, and jujube to 10 times the amount of water and decoct twice, the first decoction time is 60 minutes, the second decoction time is 40 minutes, and the combined filtrate is concentrated to 200-250 mL; Deep eutectic solvent extraction layer: Perilla leaves, Pueraria root, charcoal-processed Schizonepeta tenuifolia, vinegar-processed Cyperus rotundus are mixed with a deep eutectic solvent, the solvent is a molar ratio of choline chloride to lactic acid of 1:1-3, the water content is 25-35%, the medicinal material to solvent ratio is 1g:13-17mL, microwave-assisted extraction, microwave power 280-320W, temperature 45-55°C, time 15-25 minutes, and the extract is filtered;

[0011] (3) The aqueous extract and the deep eutectic solvent extract were combined, and the impurities were removed by centrifugation at 7500-8500 rpm for 10-20 min. The product was purified using an ultrafiltration membrane with a molecular weight cutoff of 3-8 kDa. After lyophilization, the product was redissolved in physiological saline, the pH was adjusted to 6.5-7.2, and 0.05-0.15% sodium hyaluronate was added.

[0012] In some embodiments, the deep eutectic solvent in step (2) is a choline chloride to lactic acid solution with a molar ratio of 1:2 and a water content of 28-32%.

[0013] In some embodiments, the microwave-assisted extraction in step (2) is performed at a power of 300 W, a temperature of 48-52° C., and a time of 20 min.

[0014] In some embodiments, the ultrafiltration membrane in step (3) has a molecular weight cutoff of 4.5-5.5 kDa, and 0.1% sodium hyaluronate is added after freeze-drying and reconstitution.

[0015] Compared with the prior art, the present invention has at least the following beneficial effects:

[0016] (1) The present invention uses Astragalus as the main drug, Adenophora australis as the auxiliary drug, Cyperus rotundus, Perilla frutescens leaves, and Pueraria root as the adjuvant drugs, and Schizonepeta tenuifolia carbonized as the guiding drug to form a synergistic effect of "tonifying qi and nourishing yin - dispersing wind and moistening eyes", which significantly improves the therapeutic effect of dry eye.

[0017] (2) The present invention combines the traditional processing technology with the low eutectic solvent extraction technology, combining the three-step process of traditional processing, step-by-step extraction, and precise purification to efficiently enrich the active ingredients and improve stability and efficacy.

[0018] In summary, the present invention reduces the irritation of medicinal materials through ancient processing technology, combines modern low eutectic solvent extraction technology to simultaneously enrich water-soluble and fat-soluble components, and adopts a preservative-free freeze-drying process to improve safety, providing a better choice for patients with dry eye. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 : Statistical table of irritation results for Example 1-3 groups, Comparative Example 2 group, and negative control group;

[0020] Figure 2 : Statistical table of tear secretion of blank control group, model control group, positive control group, Example 1-3 groups and Comparative Example 1-5 groups;

[0021] Figure 3 : Statistical table of corneal staining scores for blank control group, model control group, positive control group, Example 1-3 groups and Comparative Example 1-5 groups. DETAILED DESCRIPTION

[0022] The present application will be further described in detail below with reference to specific embodiments. The present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to provide a more thorough and comprehensive understanding of the present application's disclosure.

[0023] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application pertains. The terms used herein in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application.

[0024] The present invention first provides a pure traditional Chinese medicine eye drop for treating dry eye. The eye drop is prepared from the following traditional Chinese medicine raw materials in the following weight ratios through traditional processing methods: 18-28 parts of astragalus, 12-18 parts of northern adenophora, 7-11 parts of cyperus, 6-9 parts of perilla leaves, 10-14 parts of kudzu root, 7-11 parts of schizonepeta, and 6-9 parts of jujube; wherein the astragalus is honey-roasted astragalus, and the weight ratio of honey to astragalus is 1:4-6; the schizonepeta is charcoal-processed, and the carbonization temperature is 170-190°C; and the cyperus is vinegar-processed, and the soaking time in rice vinegar is 5-7 hours.

[0025] Dry eye syndrome is classified in Traditional Chinese Medicine as "white and astringent" and "drying of the spirit fluid." Its pathogenesis is primarily due to deficiency of both Qi and Yin, manifested by insufficient tear production, and secondary to stagnation of wind-heat, manifested by rapid tear evaporation. The present invention's formula is based on the principle of "tonifying Qi and nourishing Yin, dispersing wind and moistening the eyes," and the following monarch, minister, adjuvant, and guiding ingredients are used:

[0026] Main drug: Astragalus, which replenishes Qi and strengthens the exterior, invigorates Qi and produces body fluids. It is the core drug of "strong Qi leads to the production of body fluids" and targets the root cause of Qi and Yin deficiency.

[0027] Assistant medicine: Adenophora radix, nourishes yin and clears the lungs, promotes fluid production and moistens the eyes, and synergizes with Astragalus membranaceus to enhance the effect of replenishing both qi and yin.

[0028] Adjuvants: Cyperus rotundus, processed with vinegar, soothes liver qi and relieves depression, promotes qi circulation and unclogs meridians, alleviating eye dryness caused by liver qi stagnation. When combined with the main herb, unblocking qi promotes the upward flow of body fluids. Perilla leaf relieves exterior wind and promotes lung qi, regulating tear film stability as the lung governs the skin and fur. Its volatile oil components promote local microcirculation. Pueraria root: Promotes yang and produces fluid, improving eye malnutrition. Puerarin dilates blood vessels on the ocular surface, increasing nutrient supply.

[0029] The adjuvant: Schizonepeta tenuifolia, after charring, dispels wind and stops bleeding, astringes and relieves itching, and alleviates ocular irritation; it also guides the drug upward, directly reaching the eye. Jujube: Harmonizes the other herbs, tonifies the spleen and stomach, and prevents cold and cooling herbs from damaging the middle part of the body. Its polysaccharide content increases the viscosity of the drug solution, prolonging its retention time on the ocular surface.

[0030] In some embodiments, the medicine is prepared from the following Chinese medicines in the following weight ratios: 20-25 parts of Astragalus, 14-16 parts of Glehnia littoralis, 8-10 parts of Cyperus rotundus, 7-8 parts of Perilla leaves, 11-13 parts of Pueraria root, 8-10 parts of Schizonepeta tenuifolia, and 7-8 parts of jujube.

[0031] In some embodiments, the weight ratio of honey to astragalus in the honey-roasted astragalus is 1:5, the carbonization temperature of the charcoal-prepared schizonepeta is 180° C., and the soaking time of the vinegar-prepared cyperus rotundus in rice vinegar is 6 hours.

[0032] The present invention also provides a method for preparing pure Chinese herbal eye drops for treating dry eye, comprising the following steps:

[0033] (1) Mix astragalus and honey in appropriate proportions, stir-fry over low heat until the surface turns dark yellow, and obtain honey-roasted astragalus; stir-fry schizonepeta at 170-190°C until the surface turns black, and obtain charcoal-roasted schizonepeta; soak cyperus rotundus in rice vinegar for 5-7 hours, stir-fry until dry, and obtain vinegar-roasted cyperus rotundus;

[0034] (2) Water extraction layer: Add honey-roasted Astragalus, Glehnia littoralis, and jujube to 10 times the amount of water and decoct twice, the first decoction time is 60 minutes, the second decoction time is 40 minutes, and the combined filtrate is concentrated to 200-250 mL; Deep eutectic solvent extraction layer: Perilla leaves, Pueraria root, charcoal-processed Schizonepeta tenuifolia, vinegar-processed Cyperus rotundus are mixed with a deep eutectic solvent, the solvent is a molar ratio of choline chloride to lactic acid of 1:1-3, the water content is 25-35%, the medicinal material to solvent ratio is 1g:13-17mL, microwave-assisted extraction, microwave power 280-320W, temperature 45-55°C, time 15-25 minutes, and the extract is filtered;

[0035] (3) The aqueous extract and the deep eutectic solvent extract were combined, and the impurities were removed by centrifugation at 7500-8500 rpm for 10-20 min. The product was purified using an ultrafiltration membrane with a molecular weight cutoff of 3-8 kDa. After lyophilization, the product was redissolved in physiological saline, the pH was adjusted to 6.5-7.2, and 0.05-0.15% sodium hyaluronate was added.

[0036] In some embodiments, the deep eutectic solvent in step (2) is a choline chloride to lactic acid mixture having a molar ratio of 1:2 and a water content of 28-32%.

[0037] In some embodiments, the microwave-assisted extraction in step (2) is performed at a power of 300 W, a temperature of 48-52° C., and a time of 20 min.

[0038] In some embodiments, the ultrafiltration membrane in step (3) has a molecular weight cutoff of 4.5-5.5 kDa, and 0.1% sodium hyaluronate is added after freeze-drying and reconstitution.

[0039] Example 1

[0040] A pure Chinese herbal eye drop for treating dry eye is prepared from the following Chinese herbal medicines in the following weight ratio: 20g of Astragalus, 15g of Glehnia littoralis, 9g of Cyperus rotundus, 7g of Perilla leaf, 12g of Pueraria root, 9g of Schizonepeta tenuifolia, and 8g of jujube.

[0041] Preparation method:

[0042] (1) Mix Astragalus and honey in a ratio of 1:5, and stir-fry over low heat until the surface turns dark yellow to obtain honey-roasted Astragalus; stir-fry Schizonepeta tenuifolia at 180°C until the surface turns black to obtain charred Schizonepeta tenuifolia; soak Cyperus rotundus in rice vinegar for 6 hours, stir-fry until dry to obtain vinegar-roasted Cyperus rotundus;

[0043] (2) Water extraction layer: Add honey-roasted Astragalus membranaceus, Glehnia littoralis, and jujube into 200 mL of water and decoct twice, the first decoction time is 60 min, the second decoction time is 40 min, and the combined filtrate is concentrated to 220 mL; Deep eutectic solvent extraction layer: Perilla leaves, Pueraria root, charcoal-processed Schizonepeta tenuifolia, and vinegar-processed Cyperus rotundus are mixed with a deep eutectic solvent, wherein the solvent is a molar ratio of choline chloride to lactic acid of 1:2, a water content of 30%, and a medicinal material to solvent ratio of 1 g:15 mL. Microwave-assisted extraction is performed at a microwave power of 300 W, a temperature of 50°C, and a time of 20 min. Filter to obtain 150 mL of the extract;

[0044] (3) The aqueous extract and the low eutectic solvent extract were combined, and the impurities were removed by centrifugation at 8000 rpm for 15 min. The product was purified by ultrafiltration membrane with a molecular weight cutoff of 5 kDa. After lyophilization, it was redissolved in physiological saline, the pH was adjusted to 6.8, 0.1% sodium hyaluronate was added, and the product was packaged into 5 mL eye drops.

[0045] Example 2

[0046] A pure Chinese herbal eye drop for treating dry eye is prepared from the following Chinese herbal medicines in the following weight ratio: 28g of Astragalus, 18g of Glehnia littoralis, 11g of Cyperus rotundus, 9g of Perilla leaf, 14g of Pueraria root, 11g of Schizonepeta tenuifolia, and 9g of jujube.

[0047] Preparation method:

[0048] (1) Mix Astragalus and honey in a ratio of 1:6, and stir-fry over low heat until the surface turns dark yellow to obtain honey-roasted Astragalus; stir-fry Schizonepeta tenuifolia at 190°C until the surface turns black to obtain charred Schizonepeta tenuifolia; soak Cyperus rotundus in rice vinegar for 7 hours, stir-fry until dry to obtain vinegar-roasted Cyperus rotundus;

[0049] (2) Water extraction layer: Add honey-roasted Astragalus, Glehnia littoralis, and jujube into 250 mL of water and decoct twice, with the first decoction time being 60 min and the second decoction time being 40 min. The combined filtrate is concentrated to 220 mL. Deep eutectic solvent extraction layer: Perilla leaves, Pueraria root, charcoal-processed Schizonepeta tenuifolia, and vinegar-processed Cyperus rotundus are mixed with a deep eutectic solvent, wherein the solvent is a molar ratio of choline chloride to lactic acid of 1:2, a water content of 30%, and a medicinal material to solvent ratio of 1 g:17 mL. Microwave-assisted extraction is performed at a microwave power of 320 W, a temperature of 50°C, and a time of 15 min. Filter to obtain 150 mL of the extract.

[0050] (3) The aqueous extract and the low eutectic solvent extract were combined, and the impurities were removed by centrifugation at 8000 rpm for 15 min. The product was purified by ultrafiltration membrane with a molecular weight cutoff of 5 kDa. After lyophilization, it was redissolved in physiological saline, the pH was adjusted to 6.8, 0.1% sodium hyaluronate was added, and the product was packaged into 5 mL eye drops.

[0051] Example 3

[0052] A pure Chinese herbal eye drop for treating dry eye is prepared from the following Chinese herbal medicines in the following weight ratio: 18g of Astragalus, 12g of Glehnia littoralis, 7g of Cyperus rotundus, 6g of Perilla leaf, 10g of Pueraria root, 7g of Schizonepeta tenuifolia, and 6g of jujube.

[0053] Preparation method:

[0054] (1) Mix Astragalus and honey in a ratio of 1:4, and stir-fry over low heat until the surface turns dark yellow to obtain honey-roasted Astragalus; stir-fry Schizonepeta tenuifolia at 170°C until the surface turns black to obtain charred Schizonepeta tenuifolia; soak Cyperus rotundus in rice vinegar for 5 hours, stir-fry until dry to obtain vinegar-roasted Cyperus rotundus;

[0055] (2) Water extraction layer: Add honey-roasted Astragalus, Glehnia littoralis, and jujube into 200 mL of water and decoct twice, the first decoction time is 60 min, the second decoction time is 40 min, and the combined filtrate is concentrated to 200 mL; Deep eutectic solvent extraction layer: Perilla leaves, Pueraria root, charcoal-processed Schizonepeta tenuifolia, and vinegar-processed Cyperus rotundus are mixed with a deep eutectic solvent, wherein the solvent is a molar ratio of choline chloride to lactic acid of 1:2, a water content of 30%, and a medicinal material to solvent ratio of 1 g:13 mL. Microwave-assisted extraction is performed at a microwave power of 280 W, a temperature of 50°C, and a time of 20 min. Filter to obtain 150 mL of the extract;

[0056] (3) The aqueous extract and the low eutectic solvent extract were combined, and the impurities were removed by centrifugation at 8000 rpm for 15 min. The product was purified by ultrafiltration membrane with a molecular weight cutoff of 5 kDa. After lyophilization, it was redissolved in physiological saline, the pH was adjusted to 6.8, 0.1% sodium hyaluronate was added, and the product was packaged into 5 mL eye drops.

[0057] Comparative Example 1

[0058] All medicinal materials were directly decocted in water without stepwise extraction and without using a deep eutectic solvent. The rest was the same as in Example 1.

[0059] Comparative Example 2

[0060] Raw Astragalus, raw Schizonepeta and raw Cyperus were used to replace the Astragalus, Schizonepeta and Cyperus processed by traditional methods, and the rest was the same as in Example 1.

[0061] Comparative Example 3

[0062] The amount of Astragalus was changed to 15 g, the amount of Schizonepeta was changed to 13 g, and the rest was the same as in Example 1.

[0063] Comparative Example 4

[0064] Except for Perilla Leaf and Pueraria lobata, the rest is the same as in Example 1.

[0065] Comparative Example 5

[0066] Add 10g of Scutellaria baicalensis and 6g of Chrysanthemum, and the rest is the same as Example 1.

[0067] The beneficial effects of the present invention are demonstrated through safety and efficacy experiments below.

[0068] Rabbit eye irritation test

[0069] Grouping: 20 healthy New Zealand rabbits, with an average weight of 2.5-3.0 kg and no eye disease, were randomly divided into 5 groups:

[0070] Example 1-3 group: eye drops prepared in Example 1-3;

[0071] Comparative Example 2: eye drops prepared from unprocessed medicinal materials;

[0072] Negative control group: normal saline.

[0073] Dosing: 4 times a day, at 8:00, 12:00, 16:00, and 20:00, instill 50 μL of the drug solution into each eye for 7 consecutive days.

[0074] Efficacy evaluation:

[0075] The scoring criteria are as follows:

[0076] Conjunctival injection: 0-3 points, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.

[0077] Corneal edema: 0-4 points, where 0 = clear, 1 = slightly cloudy, 2 = visible iris, 3 = blurred iris, and 4 = opaque cornea.

[0078] Secretion: 0-3 points, where 0 = none, 1 = small, 2 = moderate, and 3 = large.

[0079] Table 1 Statistics of irritation results of Example 1-3, Comparative Example 2, and Negative Control Group

[0080] Grouping conjunctival congestion Corneal edema secretions Overall rating Example 1 0.2±0.1 0.0±0.0 0.1±0.1 0.3±0.2 Example 1 0.3±0.1 0.2±0.1 0.2±0.1 0.7±0.3 Example 1 0.2±0.1 0.3±0.3 0.3±0.3 0.8±0.7 Comparative Example 2 2.2±0.1* 1.3±0.3* 1.5±0.5* 5±0.9* Negative control group 0.0±0.0 0.0±0.0 0.0±0.0 0.0±0.0

[0081] Note: * indicates P < 0.01 compared with the example group.

[0082] As shown in Table 1, the total irritation score of the Example group was significantly lower than that of the unprocessed Comparative Example 2 group (P<0.01), indicating that the processing technology can effectively reduce ocular surface irritation. Among them, charcoal-processed Schizonepeta tenuifolia reduces the content of volatile oil, vinegar-processed Cyperus rotundus neutralizes acidic components and avoids pH imbalance after eye drops, and ultrafiltration membrane purification further removes sensitizing tannins with a molecular weight greater than 5 kDa, reducing the incidence of allergic reactions. The combination of the three works synergistically to reduce ocular surface irritation.

[0083] Mouse dry eye model experiment

[0084] Modeling: SPF-grade BALB / c mice, half male and half female, weighing 18-22g, were randomly divided into 11 groups of 5 mice after 7 days of adaptive feeding. 5μL of 0.2% benzalkonium chloride solution was dripped into the right eye three times daily at 8:00, 12:00, and 16:00 for 7 consecutive days. The ocular surface of the mice was observed during this period. If dry eye symptoms such as decreased tear production and corneal roughness were observed, the modeling was successful.

[0085] Grouping: blank control group: normal feeding, no treatment; model control group: only induced dry eye model, no treatment; positive control group: 0.15% sodium hyaluronate eye drops (commercially available artificial tears); Example 1-3 group: eye drops of the present invention (prepared in Example 1-3); Comparative Example 1-5 group: eye drops prepared according to Comparative Example 1-5.

[0086] Dosing: Example group and comparative example group: eye drops 3 times a day, 5 μL each time; positive control group: the same as the example group; model control group: drop the same amount of normal saline; blank control group: drop the same amount of normal saline. Administer the drug for 14 consecutive days.

[0087] Efficacy evaluation:

[0088] (1) Mice were anesthetized by intraperitoneal injection of 0.1% sodium pentobarbital. A standardized Schirmer test paper was placed on the middle and outer 1 / 3 of the lower eyelid of the right eye of the mouse for 5 minutes. The wet length of the test paper was measured (mm) and the data was recorded. The tear secretion volume after modeling and 14 days later was recorded separately.

[0089] (2) Add 5 μL of 1% sodium fluorescein solution to the conjunctival sac of the right eye of the mouse. Gently rub the eyelid to ensure uniform staining. Rinse the excess dye with saline. Observe the corneal damage under cobalt blue light of a slit lamp. Scoring criteria: Divide the cornea into 4 quadrants, and score each quadrant based on the density of staining points: 0 points: no staining; 1 point: 1-30 points; 2 points: more than 30 points; 3 points: fused into a sheet. Record the scores immediately after modeling and 14 days later.

[0090] Results and Discussion:

[0091] Table 2 Statistics of tear secretion in blank control group, model control group, positive control group, Example 1-3 groups and Comparative Example 1-5 groups

[0092] Grouping Tear secretion volume after modeling (mm) Tear secretion volume after 14 days of administration (mm) Blank control group 12.23±0.53 12.12±0.67 Model control group 3.53±0.46 3.35±0.55* Example 1 3.61±0.37 8.61±0.75#▲ Example 2 3.50±0.46 8.32±0.63#▲ Example 3 3.39±0.54 7.97±0.54#▲ Comparative Example 1 3.56±0.39 5.21±0.44 Comparative Example 2 3.70±0.30 4.17±0.33 Comparative Example 3 3.62±0.44 5.79±0.51 Comparative Example 4 3.59±0.45 4.97±0.40 Comparative Example 5 3.60±0.41 5.41±0.61 Positive control group 3.53±0.50 6.71±0.75#

[0093] Note: *: compared with the blank control group, P < 0.01; #: compared with the model control group, P < 0.01; ▲: compared with the positive control group, P < 0.05. Table 3 Statistical table of corneal staining scores for the blank control group, model control group, positive control group, Example 1-3 groups, and Comparative Example 1-5 groups

[0094] Grouping Corneal staining score after modeling Corneal staining score after 14 days of administration Blank control group 0.21±0.16 0.18±0.14 Model control group 2.71±0.29 2.69±0.23* Example 1 2.82±0.15 0.89±0.24#▲ Example 2 2.66±0.31 0.92±0.25#▲ Example 3 2.62±0.31 1.12±0.39#▲ Comparative Example 1 2.58±0.40 1.91±0.42 Comparative Example 2 2.67±0.30 2.37±0.32 Comparative Example 3 2.60±0.31 1.81±0.32 Comparative Example 4 2.70±0.22 2.12±0.43 Comparative Example 5 2.73±0.25 1.71±0.34 Positive control group 2.74±0.24 1.52±0.36#

[0095] Note: *: compared with the blank control group, P < 0.01; #: compared with the model control group, P < 0.01; ▲: compared with the positive control group, P < 0.05.

[0096] As can be seen from the above, the tear secretion volume and corneal staining score of the embodiment group after treatment were better than those of the positive control group, indicating that the Chinese medicine eye drops of the present invention effectively promote the secretory function of the lacrimal gland through the synergistic effect of the dual mechanisms of "replenishing qi and nourishing yin, dispersing wind and moistening eyes"; the tear recovery value of comparative example 2 is the lowest, proving that the ancient preparation process is an important factor in improving the efficacy; comparative example 1 uses the water decoction method, and the efficacy is lower than that of the embodiment group, verifying that the low eutectic extraction technology improves the enrichment efficiency and enrichment components, plays a role in regulating tear secretion and stabilizing the tear film; the efficacy of comparative examples 4-5 is also lower than that of the embodiment group, confirming the rationality of the original formula compatibility. Adding medicinal materials such as Scutellaria baicalensis and Chrysanthemum or reducing medicinal materials may introduce new ingredients, destroy the original mechanism of action, and reduce the efficacy.

[0097] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A pure Chinese herbal eye drop for treating dry eye, characterized in that: The invention is prepared from the following traditional Chinese medicines in the following weight proportions: 18-28 parts of astragalus, 12-18 parts of northern adenophora, 7-11 parts of cyperus, 6-9 parts of perilla leaves, 10-14 parts of kudzu root, 7-11 parts of schizonepeta, and 6-9 parts of jujube; the astragalus is honey-roasted, and the weight ratio of honey to astragalus is 1:4-6; the schizonepeta is charcoal-processed, and the carbonization temperature is 170-190°C; the cyperus is vinegar-processed, and the soaking time in rice vinegar is 5-7 hours.

2. The eye drops according to claim 1, characterized in that The medicine is prepared from the following traditional Chinese medicines in the following weight proportions: 20-25 parts of astragalus, 14-16 parts of northern adenophora, 8-10 parts of cyperus, 7-8 parts of perilla leaves, 11-13 parts of kudzu root, 8-10 parts of schizonepeta and 7-8 parts of jujube.

3. The eye drops according to claim 1, characterized in that The weight ratio of honey to astragalus in the honey-roasted astragalus is 1:5, the carbonization temperature of the charcoal-processed schizonepeta is 180° C., and the soaking time of the vinegar-processed cyperus rotundus in rice vinegar is 6 hours.

4. A method for preparing the pure Chinese herbal eye drops for treating dry eye according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) Mix astragalus and honey in appropriate proportions, stir-fry over low heat until the surface turns dark yellow, and obtain honey-roasted astragalus; stir-fry schizonepeta at 170-190°C until the surface turns black, and obtain charcoal-roasted schizonepeta; soak cyperus rotundus in rice vinegar for 5-7 hours, stir-fry until dry, and obtain vinegar-roasted cyperus rotundus; (2) Water extraction layer: Add honey-roasted Astragalus, Glehnia littoralis, and jujube to 10 times the amount of water and decoct twice, the first decoction time is 60 minutes, the second decoction time is 40 minutes, and the combined filtrate is concentrated to 200-250 mL; Deep eutectic solvent extraction layer: Perilla leaves, Pueraria root, charcoal-processed Schizonepeta tenuifolia, vinegar-processed Cyperus rotundus are mixed with a deep eutectic solvent, the solvent is a molar ratio of choline chloride to lactic acid of 1:1-3, the water content is 25-35%, the medicinal material to solvent ratio is 1g:13-17mL, microwave-assisted extraction, microwave power 280-320W, temperature 45-55°C, time 15-25 minutes, and the extract is filtered; (3) The aqueous extract and the deep eutectic solvent extract were combined, and the impurities were removed by centrifugation at 7500-8500 rpm for 10-20 min. The product was purified using an ultrafiltration membrane with a molecular weight cutoff of 3-8 kDa. After lyophilization, the product was redissolved in physiological saline, the pH was adjusted to 6.5-7.2, and 0.05-0.15% sodium hyaluronate was added.

5. The preparation method according to claim 4, characterized in that The deep eutectic solvent in step (2) is a choline chloride to lactic acid mixture having a molar ratio of 1:2 and a water content of 28-32%.

6. The preparation method according to claim 4, characterized in that The power of the microwave-assisted extraction in step (2) is 300 W, the temperature is 48-52° C., and the time is 20 min.

7. The preparation method according to claim 4, characterized in that The ultrafiltration membrane in step (3) has a molecular weight cutoff of 4.5-5.5 kDa, and 0.1% sodium hyaluronate is added after freeze-drying and re-dissolution.

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