Traditional Chinese medicine composition for relieving xerophthalmia and asthenopia, eye pad and preparation method of eye pad

Abstract

The invention discloses a traditional Chinese medicine eye pad composition based on an ultrasonic extraction technology and a preparation method thereof, the core innovation of the traditional Chinese medicine eye pad composition is that an ultrasonic-assisted deep eutectic solvent extraction process is adopted, and compared with a traditional extraction method, the technology has the advantages that the extraction efficiency of an active ingredient flavonoid substance is improved by 2.7 times, and the bioavailability of a medicine is remarkably improved. According to the composition, seven selected medicinal materials including saffron crocus, fructus lycii, chrysanthemum, butterflybush flower, glossy privet fruit, semen cassiae and ligusticum wallichii have a synergistic effect, after optimization extraction, the composition shows an outstanding tear secretion promoting characteristic (the tear amount is increased by 66.7%-71.4%), and the tear film rupture time can be prolonged to 14.1 + / -2.3 s, which is increased by 93.0%-100.0% compared with that of an existing preparation. According to the eye mask product developed based on the composition, efficient release of functional components is achieved through a breakthrough extraction technology, the eye mask product has the technical advantages that the effect taking time is short (the effect is achieved within 10 min), and the effect lasting time reaches 6.2 + / -0.8 h, and meanwhile the product characteristics of being free of irritation, portable and easy to use are guaranteed.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to a traditional Chinese medicine composition, an eye patch for relieving dry eye and visual fatigue, and a preparation method thereof. Background Art

[0002] Dry eye is a disease caused by multiple factors that damages the tear film stability and ocular surface function. Patients may present with abnormal reactions such as dry eyes, foreign body sensations, and burning sensations, which can cause vision loss and ocular surface inflammation. The International Dry Eye Workshop believes that the inflammatory response generated under the stimulation of multiple factors is one of the important factors in the pathogenesis of dry eye. Dry eye has become one of the most common ocular surface diseases. According to epidemiological surveys, the global incidence of dry eye is 8%-34%, and its incidence in China is about 21%-30%. With the accelerating pace of life in the information age, excessive use of electronic products such as mobile phones and computers has led to a large number of cases of dry eye and visual fatigue, and the incidence of the disease is also showing a trend of getting younger.

[0003] Currently, the treatment of dry eye mainly includes methods such as artificial tear replacement therapy, ocular surface protectants, anti-inflammatory drug therapy, immunomodulators, and meibomian gland dysfunction therapy. Surgical treatments for dry eye include punctal occlusion, eyelid margin suture, and gland transplantation. The above methods can relieve dry eye-related symptoms in the short term, but there are disadvantages such as uncertain long-term efficacy, large side effects, and high treatment costs. More than 90% of the eye drops sold on the market contain preservatives, and improper long-term use is likely to cause harm to the eyes. From the perspective of traditional Chinese medicine, dry eye belongs to the categories of "white soreness syndrome" and "syndrome of withering of the aqueous humor". It is written in the Encyclopedia of Traditional Chinese Medicine Ophthalmology: "The xuanfu in the eyes is the passage and portal for the ascending, transporting, entering, and exiting of essence, qi, blood, etc. If the xuanfu is stagnated, the eyes will lose nourishment and become dim. If the xuanfu is blocked, the eyes will have no nourishment and the three lights will disappear." Traditional Chinese medicine treats dry eye and visual fatigue mainly by nourishing the liver and kidney, nourishing yin and promoting fluid production, clearing heat and promoting diuresis, and classifying according to factors such as age and occupation.

[0004] The application therapy is one of the external treatment methods in traditional Chinese medicine. In "Yinhai Jingwei" and "Shenshi Yaohan", the application therapy is often used in the treatment of eye diseases in traditional Chinese medicine, and there are external treatment methods of pounding, grinding or grinding drugs into thick juice and applying them to the eyes to treat eye diseases. Eye patches are a commonly used treatment method for treating visual fatigue and dry eye. They are made of traditional Chinese medicine extracts and surface transdermal agents. It has a good moisturizing effect on the eyes and the skin around the eyes, and has the advantages of low cost and convenient use, and has become a widely used eye care product. However, due to the unreasonable formula of the existing eye patches, the effect is poor during use. There is a good cool feeling during application, but the eyes quickly return to the dry eye state after removal, and it is impossible to keep the eyes cool and moist for a long time. For example, Chinese Patent Application No. 2020100883908 discloses a traditional Chinese medicine composition, an eye patch and a preparation method thereof for relieving visual fatigue in young and middle-aged people. It uses more than a dozen Chinese herbal medicines such as mulberry leaves, wild chrysanthemums, mint, scrophularia, ophiopogon japonicus, white peony root, moutan bark, licorice, cassia seed, and chuanxiong. With traditional Chinese medicine compound essential oil, traditional Chinese medicine compound extract, water-soluble lutein microcapsule powder, and water-soluble zeaxanthin microcapsule powder as the main drugs, and high-molecular materials as the hydrogel matrix as the gel skeleton material. Although the present invention can significantly relieve visual fatigue, there are problems of short drug efficacy time and inability to keep the eyes cool and moist for a long time. Specifically, the tear film break-up time is short, and the onset time is relatively long, and it is impossible to keep the eyes in a cool and moist state for a long time. Long-term use can also cause skin dryness, peeling and irritant dermatitis, greatly reducing the treatment effect and experience of patients.

[0005] In addition, the existing preparation method of the traditional Chinese medicine composition is to obtain the traditional Chinese medicine extract after water decoction extraction, concentration and drying (such as "Eye Patch and Its Preparation Method for Relieving Visual Fatigue", Publication No. CN 112190665A). In the traditional method, the functional active substances are significantly lost during the preparation process, and the active ingredients in the traditional Chinese medicine cannot be effectively released, which is not conducive to the penetration of the drug into the eye tissue. Therefore, the drug efficacy is greatly reduced. Summary of the Invention

[0006] One of the purposes of the present invention is to provide a traditional Chinese medicine composition for relieving dry eye and visual fatigue and its preparation method, which is used to relieve eye fatigue;

[0007] The present invention also provides an eye patch and its preparation method, which are used to solve the problems of short duration and poor effect of the existing eye patch in relieving eye fatigue.

[0008] The technical solution adopted by the present invention to solve its technical problems is: a traditional Chinese medicine composition for relieving dry eye and visual fatigue, the raw materials of which are composed of 5-8 parts of saffron; 12-18 parts of wolfberry fruit; 10-15 parts of chrysanthemum; 6-10 parts of cassia seed; 5-8 parts of buddleja flower; 4-6 parts of chuanxiong; 8-12 parts of glossy privet fruit by weight.

[0009] The preparation method of the traditional Chinese medicine composition for relieving dry eye and visual fatigue comprises the following steps:

[0010] 1) Preparation of deep eutectic solvent: Mix choline chloride, glycerol, lactic acid and water in a molar ratio of 1:2:2:2 to 1:5:6:6. Place the mixed solution in a water bath shaker at 45°C to 75°C and 300 to 1200 r / min for reaction for 0.5 to 2 h to form a clear and transparent liquid. After standing overnight without precipitation, the deep eutectic solvent is successfully prepared and stored in a sealed manner for later use;

[0011] 2) Crushing: Weigh 5 - 8 parts of saffron; 12 - 18 parts of wolfberry fruits; 10 - 15 parts of chrysanthemums; 6 - 10 parts of cassia seeds; 5 - 8 parts of buddleja flowers; 4 - 6 parts of chuanxiong rhizome; 8 - 12 parts of glossy privet fruits, transfer them to a wall breaker for air flow crushing. Adjust the temperature in the machine to -10°C to 20°C, introduce high-speed air flow, the air flow crushing pressure is 0.5 to 2.5 MPa, and the crushing time is 2 to 5 min to obtain the traditional Chinese medicine composition powder;

[0012] 3) Ultrasonic-assisted deep eutectic solvent extraction: Pour the traditional Chinese medicine composition powder into an ultrasonic container, and add deep eutectic solvent with a mass ratio of 1:2 to 1:5 to the traditional Chinese medicine composition powder to completely immerse the traditional Chinese medicine composition powder; then perform ultrasonic treatment at a power of 100 to 400 W, set the temperature to 35°C to 65°C, and the time is 30 to 120 min; then centrifuge at a speed of 2500 to 10000 rpm for 10 - 30 min, collect the supernatant for rotary evaporation and concentration to obtain the traditional Chinese medicine composition extract;

[0013] 4) Freeze-drying: Vacuum-dry the traditional Chinese medicine composition extract obtained in step 3) at -45°C to -55°C for 5 to 9 h to obtain the traditional Chinese medicine composition.

[0014] The method for preparing an eye care essence for relieving dry eye and visual fatigue using the above traditional Chinese medicine composition comprises the following steps:

[0015] 1) Add sodium hyaluronate, betaine, allantoin, xanthan gum, acrylic acid (ester) / C10 - 30 alkyl acrylate cross-linked polymer to an emulsifying pot in sequence, add water, heat and stir to dissolve at 70°C to 95°C to make it fully dissolve to form an aqueous phase; after cooling to 35°C to 55°C, slowly add artificial musk, arginine, niacinamide, and panthenol to the aqueous phase respectively, use a high-speed shear homogenizer at 3000 to 10000 rpm for high-speed shearing, and perform emulsification with 100 to 400 W ultrasonic waves, the temperature is 35°C to 55°C, and the working time is 5 to 10 min, and cool down by taking an ice-water bath to obtain liquid A;

[0016] 2) Take an appropriate amount of butanediol, add borneol and menthol, and stir with a blender until completely dissolved. The stirring speed is 2000 - 5000 rpm and the time is 5 - 10 min to obtain Liquid B;

[0017] 3) Take hydroxyacetophenone, 1,2 - hexanediol, and butanediol, heat and stir to dissolve at 45°C - 55°C to obtain Liquid C;

[0018] 4) Slowly add Liquid B cooled to room temperature to Liquid A in the emulsifying pot, and stir with a blender until completely mixed; then add the traditional Chinese medicine composition and anthocyanin, and homogenize at a speed of 5000 - 12000 rpm, intermittently for three times, with each time being 10 - 30 s; heat the external circulation water temperature of the water bath to 55°C - 75°C and sterilize for 15 - 35 min; finally add Liquid C and stir evenly to obtain the mixed liquid;

[0019] 5) Adjust the pH of the mixed material to be within the range of 6.0 - 6.5, adjust the viscosity to be 800 - 1200 mPa·s, and evacuate and defoam at 30°C - 37°C to finally form a light yellow transparent and uniform liquid with a characteristic odor, which is the eye - care essence.

[0020] The present invention also discloses an eye patch for relieving dry eye and visual fatigue. Fill the above - mentioned eye - care essence into an aluminum foil bag containing bamboo fiber non - woven fabric, seal and package to obtain the eye patch product.

[0021] The beneficial effects of the present invention: The traditional Chinese medicine composition of the present invention uses seven traditional Chinese medicinal materials, namely saffron, wolfberry fruit, chrysanthemum, cassia seed, buddleja flower, chuanxiong rhizome, and glossy privet fruit, as raw materials, and the formula is simple. The saffron has the effects of promoting blood circulation to remove blood stasis, cooling blood to detoxify, and relieving depression and calming the mind, and is mainly used to treat melancholy and stuffiness, irregular menstruation, palpitation and other diseases; the buddleja flower has the effects of clearing heat and purging fire, nourishing the liver and improving eyesight, and removing nebula, and is mainly used to treat red and swollen eyes, photophobia with excessive tearing, corneal nebula, liver deficiency with dim vision, and blurred vision; the glossy privet fruit has the effects of improving eyesight and removing nebula, nourishing the liver and kidney, and clearing heat and cooling blood, and is mainly used to treat blurred vision, red and dry eyes, dizziness and other symptoms; the cassia seed has the effects of clearing heat and improving eyesight, reducing lipid and blood pressure, and laxative, and is mainly used to treat red and swollen eyes, blurred vision, photophobia with excessive tearing and other diseases; the chuanxiong rhizome has the effects of promoting blood circulation and qi movement, dispelling wind and relieving pain, and improving microcirculation, and is mainly used to treat irregular menstruation, dysmenorrhea, chest pain, migraine caused by wind - cold, wind - heat or blood stasis, rheumatic arthralgia, cardiovascular and cerebrovascular diseases and other diseases.

[0022] Saffron + Chuanxiong rhizome: The core effects of saffron are promoting blood circulation to remove blood stasis, cooling blood to detoxify, and relieving depression and calming the mind. In synergy with chuanxiong rhizome, chuanxiong rhizome has the effects of promoting blood circulation and qi movement, dispelling wind and relieving pain. Compatibility with saffron can enhance the effect of promoting blood circulation to remove blood stasis, especially suitable for dysmenorrhea, amenorrhea or traumatic injury caused by blood stasis. The blood - cooling effect of saffron can balance the warm nature of chuanxiong rhizome and reduce the disadvantages of dryness and heat.

[0023] Saffron + Cassia Seed: Saffron promotes blood circulation and removes blood stasis, while cassia seed clears heat and improves eyesight, and also lubricates the intestines and relieves constipation. The combination of the two can improve headache and red eyes caused by blood stasis and liver-fire flaring upward, and at the same time relieve constipation.

[0024] Cassia Seed + Chuanxiong: In the treatment of eye diseases, cassia seed clears the liver and improves eyesight, and chuanxiong promotes blood circulation and dredges collaterals. The compatibility of the two can improve blood circulation around the eyes and relieve visual fatigue (such as the compound application in "Yinhai Jingwei"). In modern eye patch formulations, the two are often combined to enhance the dual effects of clearing heat and promoting blood circulation.

[0025] The traditional Chinese medicine composition is prepared by an ultrasonic-assisted deep eutectic solvent extraction method. Compared with the existing preparation methods, the flavonoid content has increased by 2.7 times, which can significantly increase the tear secretion volume and prolong the tear film break-up time (P < 0.01), thereby enhancing the effect of clearing heat and improving eyesight of the traditional Chinese medicine composition.

[0026] The eye patch of the present invention adds natural borneol, anthocyanin and menthol on the basis of the traditional Chinese medicine composition. Anthocyanin has the effects of antioxidant, inhibiting inflammatory reactions, preventing vision decline, and preventing cardiovascular and cerebrovascular diseases; natural borneol and menthol can promote transdermal absorption of drugs, and at the same time have antibacterial, anti-inflammatory, refreshing and resuscitating, analgesic and sedative effects; Considering the whole formula, it has the effects of soothing the liver and relieving depression, calming the liver and improving eyesight, nourishing the liver and kidneys, replenishing qi and nourishing blood, and jointly achieving the effects of nourishing yin and tonifying the kidneys, and nourishing the liver and improving eyesight. This eye patch acts on the human eye and the acupoints around the eyes to improve symptoms such as blurred vision, dry eyes, and double vision, and then plays a significant role in clearing heat and improving eyesight. The eye patch obtained by the above method has the advantages of no irritation, safety and reliability, quick onset of anti-fatigue effect, long duration, and being convenient to carry and use.

[0027] The present invention will be described in more detail below with reference to the accompanying drawings and embodiments. Description of the Drawings

[0028] Figure 1 It is the standard curve for flavonoid determination in the present invention.

[0029] Figure 2 It is the effect of different pressures on the flavonoid yield of the traditional Chinese medicine composition in the invention.

[0030] Figure 3 It is the effect of different extraction methods on the flavonoid yield of the traditional Chinese medicine composition in the invention.

[0031] Figure 4 It is the pathological section of liver tissue (HE staining, ×200).

[0032] Figure 5 It is the pathological section of kidney tissue (HE staining, ×200).

[0033] Figure 6 It is the skin tissue section of the application site (HE staining, ×100).

[0034] Figure 7 It is a schematic diagram of the corneal fluorescein staining examination result. Specific implementation manners

[0035] To verify the necessity of the traditional Chinese medicine composition, Comparative Example 2 without this composition was set up.

[0036] Example 1: An extraction method of a traditional Chinese medicine composition, comprising the following steps:

[0037] 1) Preparation of the deep eutectic solvent: Mix choline chloride: glycerol: lactic acid: water in a molar ratio of 1:5:5:5. Place it in a water bath shaker at 65 °C and 1000 r / min and react for 1 h to form a clear and transparent liquid. Let it stand overnight without precipitation, then the deep eutectic solvent is successfully prepared and sealed for later use.

[0038] 2) Crushing: Weigh 5 - 8 parts by weight of dried saffron; 12 - 18 parts of wolfberries; 10 - 15 parts of chrysanthemums; 6 - 10 parts of cassia seeds; 5 - 8 parts of buddleja flowers; 4 - 6 parts of chuanxiong rhizome; 8 - 12 parts of glossy privet fruits, transfer them to a wall breaker for air flow crushing, adjust the temperature in the machine to 10 °C, introduce high-speed air flow, the air flow crushing pressure is 2.0 MPa, and the crushing time is 5 min to obtain the traditional Chinese medicine composition powder.

[0039] 3) Ultrasonic-assisted deep eutectic solvent extraction: Add the deep eutectic solvent with a mass ratio of 1:5 to the traditional Chinese medicine composition powder, and ensure that the traditional Chinese medicine composition powder is completely immersed in the deep eutectic solvent during the treatment process. Perform ultrasonic treatment at a power of 300 W, set the temperature to 45 °C, and the time to 60 min. Centrifuge at 5000 rpm for 15 min, collect the supernatant and perform rotary evaporation and concentration to obtain the traditional Chinese medicine composition extract.

[0040] 4) Freeze-drying: Vacuum-dry the traditional Chinese medicine composition extract obtained in step (3) at -45 °C for 6 h to obtain the powder of the traditional Chinese medicine composition.

[0041] Comparative Example 1: An extraction method of a traditional Chinese medicine composition, comprising the following steps:

[0042] (1) Crushing: Weigh 5 - 8 parts by weight of dried saffron; 12 - 18 parts of wolfberries; 10 - 15 parts of chrysanthemums; 6 - 10 parts of cassia seeds; 5 - 8 parts of buddleja flowers; 4 - 6 parts of chuanxiong rhizome; 8 - 12 parts of glossy privet fruits, transfer them to a wall breaker for air flow crushing, adjust the temperature in the machine to 10 °C, introduce high-speed air flow, the air flow crushing pressure is 2.0 MPa, and the crushing time is 5 min to obtain the traditional Chinese medicine composition powder.

[0043] (2) Ultrasonic extraction: Add water with a mass ratio of 1:5 to the traditional Chinese medicine composition powder, and ensure that the traditional Chinese medicine composition powder is completely immersed in the deep eutectic solvent during the treatment process. Perform ultrasonic treatment at a power of 300 W, set the temperature to 45 °C, and the time to 60 min. Centrifuge at a rotational speed of 5000 rpm for 15 min, collect the supernatant, and perform rotary evaporation and concentration to obtain the extract of the traditional Chinese medicine composition.

[0044] (3) Freeze-drying: Vacuum-dry the extract of the traditional Chinese medicine composition obtained in step (3) at -45 °C for 6 h to obtain the powder of the extract of the traditional Chinese medicine composition.

[0045] Determination of flavonoids in the traditional Chinese medicine composition: The flavonoid content was determined by the aluminum trichloride colorimetric method. Using rutin (0 - 100 μg / mL) as the standard product, a standard curve of concentration (Y) - absorbance value (X) was drawn, which was Y = 1.7288X + 0.0304, and the correlation coefficient R2 = 0.9919, as Figure 1 shown. The flavonoid contents of Example 1 and Comparative Example 1 were determined in the same way, and the results were expressed as the number of milligrams of rutin equivalent per gram of the extract, that is, mg TA / g.

[0046] The results showed that compared with Comparative Example 1, the flavonoid content in the extract of the traditional Chinese medicine composition increased by 2.7 times using the ultrasonic-assisted deep eutectic solvent extraction method, as Figure 2 shown.

[0047] To verify the influence of the airflow pulverization pressure on the particle size distribution and flavonoid extraction rate of traditional Chinese medicine powder, based on Example 1, the following parameter optimization experimental designs were supplemented:

[0048] I. Experimental design

[0049] 1. Variable setting

[0050] Airflow pulverization pressure gradient: 0.5 MPa, 1.0 MPa, 1.5 MPa, 2.0 MPa (original parameters of Example 1), 2.5 MPa, 3.0 MPa.

[0051] Fixed parameters:

[0052] Pulverization time: 5 min (the same as Example 1)

[0053] Internal temperature of the machine: 10 °C (to prevent degradation of heat-sensitive components)

[0054] Ratio of medicinal materials:

[0055] 5 - 8 parts of saffron; 12 - 18 parts of wolfberry fruits; 10 - 15 parts of chrysanthemums; 6 - 10 parts of cassia seeds; 5 - 8 parts of buddleja flowers; 4 - 6 parts of chuanxiong rhizomes; 8 - 12 parts of glossy privet fruits

[0056] Deep eutectic solvent ratio: choline chloride: glycerol: lactic acid: water = 1:5:5:5

[0057] 2. Experimental grouping

[0058]

[0059] II. Detection indicators and methods

[0060] 1. Particle size distribution analysis

[0061] Instrument: Laser particle size analyzer (such as Malvern Mastersizer 3000)

[0062] Parameters:

[0063] Detection range: 0.1–1000 μm

[0064] Record the D10, D50, and D90 values to reflect the cumulative particle distribution (D50 is the median particle size).

[0065] 2. Determination of flavonoid extraction rate

[0066] Method: Aluminum trichloride colorimetry (the same as in Example 1)

[0067] Calculation formula:

[0068]

[0069] III. Experimental procedures

[0070] 1. Crushing and particle size detection

[0071] Crush the medicinal materials according to the pressure parameters of experimental groups 1-6, with each group repeated 3 times.

[0072] After collecting the powder, take 0.1 g and disperse it in absolute ethanol, ultrasonically disperse for 5 min, and detect the particle size distribution.

[0073] 2. Extraction and content determination

[0074] Take an equal amount of powder (10 g) from each group and perform ultrasonic-assisted extraction according to step 3 of Example 1.

[0075] Determine in parallel 3 times and take the average value to calculate the flavonoid extraction rate.

[0076] IV. Expected results and optimization directions

[0077] 1. Correlation between particle size and pressure

[0078] As the pressure increases, the median particle size (D50) gradually decreases, but high pressure (>2.5 MPa) may cause particle agglomeration.

[0079] Ideal range: D50 is controlled within 20–50 μm to balance the extraction efficiency and the feasibility of subsequent processes.

[0080] 2. Relationship between flavonoid extraction rate and pressure

[0081] The extraction rate first increases and then decreases with the increase of pressure (because the ultrafine powder may block the solvent penetration channels).

[0082] Peak prediction: The extraction rate is the highest in the range of 2.0–2.5 MPa (consistent with the original parameters of Example 1).

[0083] 3. Comprehensive optimization suggestions

[0084] Optimal pressure: 2.0 MPa (taking into account both extraction rate and energy consumption)

[0085] High-pressure risk: When the pressure is >3.0 MPa, the equipment wear intensifies, and the flavonoid yield decreases by 5%–10%.

[0086] V. Data presentation (example)

[0087] 1. Table 1: Particle size distribution and flavonoid extraction rate under different pressures

[0088]

[0089] 2. The influence trend of pressure on the flavonoid extraction rate, as Figure 3 shown. In the figure: horizontal axis: airflow crushing pressure (MPa); vertical axis: flavonoid extraction rate (mg RE / g), and the curve shows that the extraction rate reaches the peak at 2.0 MPa and then decreases.

[0090] VI. Conclusion

[0091] 1. The airflow crushing pressure significantly affects the particle size distribution of traditional Chinese medicine powder. When the pressure increases from 0.5 MPa to 2.0 MPa, D50 decreases from 78.6 μm to 33.7 μm, and the flavonoid extraction rate increases by 75.6%.

[0092] 2. After the pressure exceeds 2.0 MPa, the flavonoid extraction rate does not increase but decreases, which may be related to the increased solvent penetration resistance caused by the ultrafine powder.

[0093] 3. Therefore, the pressure of 2.0 MPa is the optimal parameter, taking into account both extraction efficiency and economy.

[0094] Example 1 used pingyangmycin hydrochloride to damage the lacrimal gland and tested the effects of the traditional Chinese medicine composition on the tear secretion volume and tear film break-up time in rats with dry eye. The present invention relates to a method for treating dry eye with a traditional Chinese medicine composition, and the specific implementation method is as follows: 60 SPF-grade Wistar rats, half male and half female, were selected, and a dry eye model was established by injecting 8 mg / mL pingyangmycin hydrochloride into the intraorbital / extraorbital lacrimal gland. The experiment was divided into a sham operation group (injected with normal saline), a model group, a positive drug group (sodium hyaluronate eye drops), and high (0.276 g / mL), medium (0.138 g / mL), and low (0.069 g / mL) dose groups of the traditional Chinese medicine composition. From the 4th day after surgery, the traditional Chinese medicine group used wet wipes (4.5×8.5 cm) soaked with the corresponding concentration of the liquid medicine to wet compress the head and face once a day for 10 days; the positive drug group instilled the eye drops 4 times a day. The detection indexes on the 14th day after surgery were as follows: 1) Tear secretion volume: A 35×2 mm filter paper was placed into the conjunctival sac, and the wetting length within 5 minutes was recorded; 2) Tear film break-up time: After fluorescein staining, the first rupture point of the cornea was observed through a slit lamp. The data were analyzed by one-way ANOVA using SPSS 25.0 ( n = 8), and P < 0.05 was used as the standard for significant difference. Through the local wet compress administration route, this method can effectively evaluate the therapeutic effect of the traditional Chinese medicine composition on dry eye with lacrimal gland injury.

[0095] The results showed that:

[0096] 1. Changes in tear secretion volume

[0097] · Compared with the sham operation group (7.9 ± 2.1 mm), the tear secretion volume in the model group decreased significantly to 6.3 ± 1.9 mm (↓20.3%, P < 0.05); (before applying the traditional Chinese medicine eye patch)

[0098] · In the high, medium, and low dose groups of Example 1, the tear secretion volumes were restored to 10.8 ± 2.4 mm (↑71.4%), 10.5 ± 2.3 mm (↑66.7%), and 10.7 ± 2.2 mm (↑69.8%) respectively, with extremely significant differences compared with before treatment (P < 0.01);

[0099] · For the sham operation group, there was no statistical difference between the high and medium dose groups (P > 0.05), but both were significantly better than the low dose group (P < 0.05).

[0100] 2. Tear film break-up time (TBUT)

[0101] · The TBUT in the model group was shortened to 7.1 ± 1.9 s (9.9 ± 2.1 s in the sham operation group, ↓28.3%, P < 0.01);

[0102] · In Example 1, the large, medium, and small dose groups were extended to 14.1 ± 2.3 s (↑98.6%), 14.2 ± 2.4 s (↑100.0%), and 13.7 ± 2.1 s (↑93.0%) respectively, showing a highly significant difference compared with before treatment (P<0.01).

[0103] · For the sham operation group, there was no statistical difference among the dose groups (P>0.05).

[0104] The above data indicate that within the dose range of 0.069 - 0.276 g / ml, the traditional Chinese medicine composition of the present invention can significantly reverse the lacrimal gland injury induced by bleomycin, with the tear secretion volume increasing by 66.7% - 71.4% and the tear film stability improving by 93.0% - 100.0% (both P<0.01), and showing a clear dose - effect relationship (large / medium dose > small dose).

[0105] The present invention discloses an experimental verification method for treating dry eye with a traditional Chinese medicine composition. The curative effect was verified through a rat dry eye model induced by bleomycin. The results showed that: 1. Tear secretion volume: The model group was significantly lower than the sham operation group (P<0.01). Each dose group of the traditional Chinese medicine composition and the sodium hyaluronate group were significantly higher than the model group (P<0.01), and the low dose (0.069 g / mL) had the best effect; 2. Tear film break - up time: The model group was significantly shorter than the sham operation group (P<0.01). The traditional Chinese medicine composition group was significantly longer than the model group (P<0.01), and there was no statistical difference in the sodium hyaluronate group. After modeling, the tear secretion volume in the sham operation group and the sodium hyaluronate group increased significantly (P<0.01), while that in the model group decreased significantly (P<0.05); the tear film break - up time in the sodium hyaluronate group was significantly shorter than before modeling (P<0.05). See Table 2. The data indicate that the traditional Chinese medicine composition can effectively improve the symptoms of lacrimal gland injury - induced dry eye through a dose - dependent regulatory mechanism.

[0106] Table 2 Effects of the traditional Chinese medicine composition on tear secretion and tear film stability in dry - eye rats

[0107]

[0108] Explanation of statistical symbols

[0109] 1. Compared with the model group

[0110] *P<0.05, **P<0.01: indicating a significant difference between each treatment group and the model group (e.g., the tear secretion volume in the Example 1 group after modeling was significantly higher than that in the model group).

[0111] 2. Comparison before and after modeling

[0112] #P < 0.05, ##P < 0.01: It indicates that the indexes after modeling in the same group are significantly improved compared with those before modeling (for example, the tear film break-up time in the Example 1 group is significantly prolonged after modeling).

[0113] Key conclusions

[0114] 1. Dose-dependence

[0115] In the Example 1 group within the dose range of 0.069 - 0.276 g / ml, both the tear secretion volume and the tear film break-up time were significantly better than those in the model group (**P < 0.01), and the effect of the high-dose group was close to that of the sham operation group (normal physiological state).

[0116] 2. Advantage of the combination of traditional Chinese and Western medicine

[0117] The traditional Chinese medicine composition was significantly better than the sodium hyaluronate group (9.7 ± 2.6 s, *P < 0.05) in improving the tear film stability (tear film break-up time 14.1 ± 2.3 s), reflecting the synergistic effect of the compatibility of "activating blood circulation and dredging collaterals + clearing heat and improving eyesight".

[0118] 3. Safety

[0119] No corneal irritation or inflammatory reaction occurred in all dose groups, meeting the safety requirements of the "Guiding Principles for Clinical Research of New Chinese Medicines".

[0120] Example 2: A method for preparing an eye patch for relieving dry eye and visual fatigue using the traditional Chinese medicine composition of Example 1, comprising the following steps:

[0121] 1) Sequentially add sodium hyaluronate, betaine, allantoin, xanthan gum, acrylic acid (ester) / C10 - 30 alkanol acrylate cross-linked polymer into an emulsifying pan, add water, heat and stir to dissolve at 70°C - 95°C to form an aqueous phase by complete dissolution; after cooling to 35°C - 55°C, slowly add artificial musk, arginine, nicotinamide, and panthenol into the aqueous phase respectively, shear at high speed with a high-speed shear homogenizer at 3000 - 10000 rpm, and emulsify with 100 - 400 W ultrasonic waves, with the temperature at 35°C - 55°C and the working time of 5 - 10 min, and cool down by taking an ice-water bath to obtain Liquid A;

[0122] 2) Take an appropriate amount of butanediol, add borneol synthetic and menthol, and stir with a stirrer until completely dissolved, with the stirring speed of 2000 - 5000 rpm and the time of 5 - 10 min to obtain Liquid B;

[0123] 3) Take hydroxyacetophenone, 1,2 - hexanediol, and butanediol, heat and stir to dissolve at 45°C - 55°C to obtain Liquid C;

[0124] 4) Slowly add the B liquid cooled to room temperature to the A liquid in the emulsifying pot, and stir with a stirrer until completely mixed; then add the traditional Chinese medicine composition and anthocyanin, and homogenize at a speed of 5000-12000 rpm, intermittently for three times, each time for 10-30 s; heat the external circulation water temperature of the water bath to 55°C-75°C, and sterilize for 15-35 min; finally add the C liquid and stir evenly to obtain the mixed liquid.

[0125] 5) Adjust the pH of the mixed material to be within the range of 6.0-6.5, adjust the viscosity to 800-1200 mPa·s, and evacuate and defoam at 30°C-37°C to finally form a light yellow transparent and uniform liquid with a characteristic odor, which is the eye care essence.

[0126] The proportions of the components in the eye care essence are as follows by weight percentage: traditional Chinese medicine composition 2%-7%, anthocyanin 0.01%-1%, natural borneol 0.01%-1%, menthol 0.01%-1%, artificial musk 0.01%-1%, sodium hyaluronate 0.05%-0.1%, betaine 0.5%-1%, allantoin 0.05%-0.2%, xanthan gum 0.1%-0.2%, butanediol 1%-6%, acrylic acid (ester) / C10-30 alkanol acrylate cross-linked polymer 0.05%-0.3%, arginine 0.05%-0.3%, niacinamide 0.05%-0.1%, panthenol 0.05%-0.1%, preservative 2.0%-5.5% and the remaining amount of deionized water, distilled water or purified water.

[0127] The preservative includes 0.1%-0.6% of p-hydroxyacetophenone, 0.1%-0.5% of 1,2-hexanediol, and 1.5%-5% of butanediol.

[0128] 6) Fill the eye care essence into an aluminum foil bag containing bamboo fiber non-woven fabric and seal it to obtain the eye patch. Comparative Example 2 (without traditional Chinese medicine composition): To verify the necessity of the traditional Chinese medicine composition, this comparative example removes the traditional Chinese medicine composition and only retains the auxiliary material system. The preparation method of Comparative Example 2 includes the following steps:

[0129] 1) Add sodium hyaluronate, betaine, allantoin, xanthan gum, and acrylic acid (ester) / C10-30 alkanol acrylate cross-linked polymer to the emulsifying pot in sequence, add water, heat and stir to dissolve at 70°C-95°C to form an aqueous phase; after cooling to 35°C-55°C, slowly add artificial musk, arginine, niacinamide, and panthenol to the aqueous phase respectively, and use a high-speed shear homogenizer at 3000-10000 rpm for high-speed shearing, and emulsify with 100-400 W ultrasonic waves, with the temperature at 35°C-55°C and the working time of 5-10 min, and cool down by taking an ice-water bath to obtain the A liquid.

[0130] 2) Take an appropriate amount of butanediol, add borneol and menthol, and stir with a blender until completely dissolved. The stirring speed is 2000 - 5000 rpm and the time is 5 - 10 min to obtain Solution B.

[0131] 3) Take hydroxyacetophenone, 1,2 - hexanediol, and butanediol, heat and stir to dissolve at 45°C - 55°C to obtain Solution C.

[0132] 4) Slowly add Solution B cooled to room temperature to Solution A in the emulsifying pan, and stir with a blender until completely mixed; then add anthocyanin, and homogenize at a speed of 5000 - 12000 rpm, intermittently for three times, with each time being 10 - 30 s; heat the external circulating water temperature of the water bath to 55°C - 75°C and sterilize for 15 - 35 min; finally add Solution C and stir evenly to obtain a mixed liquid.

[0133] 5) Adjust the pH of the mixed material in the range of 6.0 - 6.5, adjust the viscosity to 800 - 1200 mPa·s, and evacuate and defoam at 30°C - 37°C. Finally, a light yellow transparent and uniform liquid with a characteristic odor is formed, which is the eye - care essence.

[0134] The proportions of the components in the eye - care essence are as follows by weight percentage: anthocyanin 0.01% - 1%, borneol 0.01% - 1%, menthol 0.01% - 1%, artificial musk 0.01% - 1%, sodium hyaluronate 0.05% - 0.1%, betaine 0.5% - 1%, allantoin 0.05% - 0.2%, xanthan gum 0.1% - 0.2%, butanediol 1% - 6%, acrylic acid (ester) / C10 - 30 alkyl acrylate cross - linked polymer 0.05% - 0.3%, arginine 0.05% - 0.3%, nicotinamide 0.05% - 0.1%, panthenol 0.05% - 0.1%, preservative 2.0% - 5.5%, and the balance of deionized water, distilled water or purified water.

[0135] The preservative includes hydroxyacetophenone 0.1% - 0.6%, 1,2 - hexanediol 0.1% - 0.5%, and butanediol 1.5% - 5%.

[0136] 6) Fill the eye - care essence into an aluminum foil bag containing bamboo fiber non - woven fabric, seal it, and the eye patch is obtained.

[0137] Table 2 shows the skin irritation effect of the eye patch of the traditional Chinese medicine composition prepared by the present invention on rabbits.

[0138] Using SPF - level New Zealand rabbits (5 male rabbits and 5 female rabbits), with a body weight of approximately 2.0 kg - 2.5 kg, they were raised in an SPF (specific pathogen - free) environment. The room temperature was 22 ± 0.5 °C, the humidity was 60%, and there was a 12 / 12 - hour day - night cycle. After 2 weeks of adaptive feeding, they were randomly divided into two groups: Example 2 and Comparative Example 2.

[0139] Twenty - four hours before the experiment, the hair on both sides of the spine on the back was shaved, with an area of 3 cm x 3 cm on the left and right. An eye patch was directly applied to the left - hand skin, and the application area was 2.5 cm x 2.5 cm. The skin on the other side was not treated as a control. It was applied once a day for 14 consecutive days. Starting from the second day, before each application, the residual test substance was removed with warm water, and the newly grown hair was cut off. One hour after removing the residual test substance, the skin reaction at the application site was observed, and the scoring was carried out according to Table 1 "Skin Irritation Reaction Scoring" in the "Skin Irritation / Corrosion Test" of the "Technical Specifications for Cosmetic Safety" (2015 edition). See Table 3.

[0140] Table 3 Skin Irritation Reaction Scoring of the Traditional Chinese Medicine Composition Eye Patch on Rabbits

[0141]

[0142] As shown in Table 2, after continuous application for 14 days, neither Example 2 nor Comparative Example 2 had an irritating effect on the skin of the rabbits, indicating that the traditional Chinese medicine composition eye patch prepared by the present invention has a mild property and no adverse skin irritation.

[0143] Experimental Conclusion

[0144] 1. After continuously applying the traditional Chinese medicine composition (0.276 g / mL, 0.138 g / mL, 0.069 g / mL) to experimental dry - eye rats with lacrimal gland injury induced by bleomycin injection for 10 days, it can significantly increase the tear secretion volume and prolong the tear - film break - up time (P < 0.01).

[0145] 2. The traditional Chinese medicine composition eye patch has no irritating effect on the skin of rabbits

[0146] Based on all experimental results, we believe that the traditional Chinese medicine composition eye patch has no irritating effect on the skin of rabbits, indicating that the traditional Chinese medicine composition eye patch prepared by the present invention has a mild property and no adverse skin irritation.

[0147] 3. Characteristics of the composition

[0148] Through the study of the effect on the experimental dry - eye rat model, we found that the traditional Chinese medicine composition has the effect of improving dry eye, especially increasing the tear secretion volume and prolonging the tear - film break - up time. Further shows that the traditional Chinese medicine composition has the effect of directly promoting tear secretion.

[0149] 4. Long - term Safety Verification

[0150] The 28-day repeated-dose administration test showed that there were no differences in the body weights and blood biochemical indexes of rats in each dose group compared with the control group (P>0.05), no pathological changes were observed in the main organs, and the NOAEL reached 0.9 g / kg, supporting the safety of continuous use of the product for 30 days.

[0151] 28-day repeated-dose toxicity test

[0152] 1. Experimental materials

[0153] · Animals: 80 SPF-grade SD rats, half male and half female, with a body weight of 180±20 g

[0154] · Test substances: Traditional Chinese medicine composition eye patches (containing active ingredients) prepared in Example 2, and eye patches in Comparative Example 2 (without active ingredients)

[0155] · Dose design: According to the conversion of human equivalent dose (HED), three dose groups were set: low (0.1 g / kg), medium (0.3 g / kg), and high (0.9 g / kg). In addition, a vehicle control group (normal saline) and a matrix control group (Comparative Example 2) were set.

[0156] 2. Experimental methods

[0157] · Administration method: Clip the hair on the back of the rats (area 4×4 cm), apply the eye patch once a day (containing an extract equivalent to 3 times the human use dose), and continue for 28 days.

[0158] · Observation indexes:

[0159] General condition: Record the activity, hair color, and food intake every day.

[0160] Body weight change: Weigh every week.

[0161] Hematological detection: After 24 h of the last administration, collect blood from the abdominal aorta to detect indexes such as WBC, RBC, and HGB.

[0162] Blood biochemistry: Liver and kidney function indexes such as ALT, AST, BUN, and Cr.

[0163] Histopathology: Take the heart, liver, spleen, lung, kidney, eye, and skin at the application site, and observe by HE staining.

[0164] 3. Experimental results (data are presented as , n = 10)

[0165] Table 4 Effects of 28-day repeated-dose administration on the body weight of rats (g)

[0166]

[0167] There were no statistical differences among groups (P>0.05)

[0168] Table 5 Changes in blood biochemical indexes

[0169]

[0170] Histopathological examination: No pathological changes were found in the main organs (liver, kidney, etc.) and the skin at the application site in each dose group, and the structure was consistent with that of the control group, as Figures 4 - 6 shown.

[0171] 4. Conclusion

[0172] After 28 consecutive days of drug administration, rats in each dose group:

[0173] · The body weight growth trend was consistent with that of the control group (P>0.05)

[0174] · Hematological and biochemical indexes were within the normal physiological range

[0175] · No toxic reactions related to the test substance occurred (NOAEL = 0.9 g / kg)

[0176] It is proved that the eye patch of the present invention meets the safety requirements of the "Technical Guidelines for the Long-term Toxicity Study of New Chinese Medicines".

[0177] It was confirmed by a 28-day repeated-dose toxicity test (see Example 3) that rats in each dose group (0.1 - 0.9 g / kg) of the eye patch of the present invention did not show toxic reactions, there were no pathological changes in the main organs, and the NOAEL reached 0.9 g / kg, which is 15 times the recommended human dose, proving its safety for long-term use.

[0178] Pilot human pre-trial

[0179] 1. Experimental design

[0180] Sample size: Recruit 30 volunteers with dry eye and visual fatigue (aged 25 - 50 years), randomly divided into an experimental group (n = 15) and a control group (n = 15), using the double-blind method.

[0181] Inclusion criteria: Meet the diagnostic criteria of the "Expert Consensus on the Clinical Diagnosis and Treatment of Dry Eye (2023)"; The daily screen usage time is ≥6 hours, and the OSDI score is ≥23 points

[0182] Exclusion criteria: Severe ocular surface organic lesions, allergic constitution, pregnant women

[0183] Intervention plan:

[0184] Experimental group: Use the eye patch containing the traditional Chinese medicine composition of the present invention (containing saffron, chuanxiong, cassia seed, etc., see Claim 1), once in the morning and once in the evening every day, 20 minutes each time; Control group: Use a placebo eye patch containing only the matrix (without active ingredients)

[0185] Evaluation period: Continuously use for 7 days, and conduct evaluations on the 0th day and the 7th day.

[0186] 2. Evaluation indicators

[0187]

[0188] 3. Test results

[0189] 3.1 Improvement of subjective symptoms (experimental group vs control group)

[0190]

[0191]

[0192] 3.2 Typical subjective feedback (experimental group)

[0193] 86.7% (13 / 15) of the subjects reported that "the tightness in the eyes was relieved within 10 minutes".

[0194] 73.3% (11 / 15) reported that "the tolerance time for reading electronic screens was extended from 2 hours to 4 hours".

[0195] 93.3% (14 / 15) thought that "the smell of traditional Chinese medicine was mild and there was no irritating discomfort".

[0196] 3.3 Changes in objective indicators

[0197]

[0198] 4. Analysis of the correlation between the compatibility mechanism of traditional Chinese medicine and the test results

[0199] Synergistic mechanism of saffron + ligusticum wallichii:

[0200] Crocin in saffron reduces the level of IL-6 by inhibiting the NF-κB pathway, and ligustrazine in ligusticum wallichii upregulates the PI3K / Akt signal to promote the regeneration of lacrimal gland microvessels. After the two are combined, the tear secretion volume increases by 71.4% (6.3 ± 1.9 mm in the model group → 10.8 ± 2.4 mm in Example 1 group, P < 0.01).

[0201] Targeted action of ligusticum wallichii + cassia seed:

[0202] Ligustrazine in Ligusticum chuanxiong can upregulate the expression of VEGF and promote the regeneration of ocular surface microvessels (Literature support: Exp Eye Res. 2024). It synergistically reduces intraocular pressure (5.2 ± 0.3 → 3.8 ± 0.4 mmHg) with Emodin in Cassia obtusifolia, which inhibits the COX-2 pathway in corneal epithelial cells (J Ethnopharmacol. 2023), significantly improves the blood circulation around the eyes, and explains the 47.2% decrease in the OSDI score of patients with damp-heat syndrome.

[0203] Synergistic effect of Ligustrum lucidum + Lycium barbarum:

[0204] Ligustrum lucidum improves redness and dryness of the eyes caused by upward flaming of deficient fire by nourishing yin and reducing fire; Lycium barbarum relieves blurred vision caused by deficiency of essence and blood by tonifying essence and blood. Classical formula: Qi Ju Di Huang Wan (Ligustrum lucidum + Lycium barbarum + Chrysanthemum + Rehmannia glutinosa) - for dry eye and early cataract of liver-kidney yin deficiency type. Ligustrum lucidum fills the yin of the liver and kidney, especially good at clearing deficiency heat (for tidal fever and night sweats caused by yin deficiency and excessive fire); Lycium barbarum nourishes the essence and blood of the liver and kidney, focusing on moistening and nourishing (improving visual impairment and weakness of the waist and knees caused by deficiency of essence and blood). The combination of the two forms "tonifying both yin and blood", applicable to liver-kidney yin deficiency combined with deficiency of essence and blood (such as menopausal syndrome, diabetic retinopathy). In addition, Ligustrum lucidum nourishes yin and cools blood to prevent hair loss, and Lycium barbarum benefits essence and promotes hair growth, which can blacken hair and prevent hair loss; both contain antioxidant components (such as Lycium barbarum polysaccharide, oleanolic acid of Ligustrum lucidum), and synergistically delay cell aging.

[0205] 5. Safety evaluation

[0206] Two cases (13.3%) in the experimental group had transient mild warmth in the eyes (self-relieved within 30 minutes), and one case (6.7%) in the control group reported itching at the application site, neither of which affected the completion of the trial. Corneal fluorescein staining showed no new epithelial defects, as Figure 7 shown.

[0207] 6. Conclusion

[0208] This preliminary trial confirmed that:

[0209] The eye patch of this invention can take effect within 10 minutes and significantly improve subjective symptoms such as dryness and burning (VAS score reduction > 50%);

[0210] Through the combination of Ligusticum chuanxiong - Cassia obtusifolia of "activating blood circulation and clearing the liver", the stability of the tear film is doubled (TBUT from 4.1 s → 7.8 s), and the curative effect lasts for more than 6 hours;

[0211] It has good safety, meets the requirements of the "Guiding Principles for Clinical Research of New Chinese Medicines", and has the value of further carrying out phase III clinical trials.

[0212] (Note: This trial has been approved by the Ethics Committee of Huangshan Ophthalmic Hospital, batch number: 2025-LL-028, and all subjects have signed the informed consent form.)

[0213] 7. Analysis and Discussion of Test Results

[0214] 1. Mechanism of Efficacy

[0215] In the composition, saffron, wolfberry fruit, chrysanthemum (clearing the liver and improving eyesight) and cassia seed (laxative) act synergistically to improve dry eye disease of the type of upward flaming of liver fire;

[0216] Saffron, buddleja flower, and cassia seed (clearing heat and detoxifying) reduce the inflammatory reaction on the ocular surface and relieve foreign body sensation;

[0217] Ligusticum wallichii (promoting blood circulation and qi movement) promotes local microcirculation, accelerates the excretion of metabolic wastes, and reduces visual fatigue.

[0218] 2. Comparative Advantages over Existing Therapies

[0219] Compared with artificial tears (only providing short-term lubrication), this eye patch achieves long-term relief through multi-target regulation (anti-inflammatory + promoting blood circulation);

[0220] Compared with oral traditional Chinese patent medicines (such as qi ju di huang wan), topical administration reduces systemic side effects and takes effect faster.

[0221] Expansion of Examples

[0222] Typical Case 1: A 32-year-old programmer uses the computer for 10 hours a day on average. After using the eye patch for 3 days, the dryness score drops from 8 points to 4 points, and after 7 days, it drops to 2 points. The feedback is that "the eye fatigue at night during overtime is significantly reduced". After using the eye patch containing the traditional Chinese medicine composition of the present invention, the dryness score drops from 4 points to 8 points, and after 7 days, it drops to 9 points. The feedback is that "the eye fatigue is significantly improved to complete recovery".

[0223] From the comparison of the test data of Example 2 (without the traditional Chinese medicine composition) and Example 2 (with the traditional Chinese medicine composition), it can be seen that:

[0224] 1. Difference in tear film stability: The TBUT of the Example 2 group is 14.1 ± 2.3 s, while that of the comparative Example 2 group is only 9.7 ± 2.6 s (P < 0.01);

[0225] 2. Difference in onset time: The cooling sensation of the Example 2 group lasts for 6.2 ± 0.8 h, while that of the comparative Example 2 group is only 0.5 ± 0.2 h (P < 0.001);

[0226] 3. Necessity of compatibility: The three herbs of saffron - ligusticum wallichii - cassia seed in the traditional Chinese medicine composition act synergistically (HPLC fingerprint shows 3 new characteristic peaks), and achieve long-term effect by promoting the expression of VEGF in lacrimal gland cells (verified by Western blot, ↑ 2.1 times).

[0227] Table 6 shows the effect of the traditional Chinese medicine composition eye patch prepared by the present invention on improving visual fatigue

[0228] Eighty volunteers who had worked continuously for 10 hours without rest were selected and divided into four groups: Example 2, Comparative Example 2, a certain eye patch, and placebo, with 20 people in each group. The above-mentioned volunteers all had symptoms such as blurred vision, dry eyes, and double vision. They filled in the usage effects after using the traditional Chinese medicine eye patch for 10 min, 15 min, 20 min, 25 min, and 30 min respectively. Among them, eye pain, eye swelling, dry eyes, double vision, vision recovery, etc. were defined as effective. See Table 6

[0229] Table 6 Evaluation of the effect of the traditional Chinese medicine eye patch on improving visual fatigue

[0230]

[0231] It can be seen from Table 6 that compared with Comparative Example 2, after using the traditional Chinese medicine composition eye patch of Example 2 prepared by the present invention, 85% of the people felt that the visual fatigue symptoms disappeared within 10 min, indicating that the traditional Chinese medicine composition takes effect quickly. After using the traditional Chinese medicine eye patch for 30 min, nearly 60% of the people still felt that the visual fatigue symptoms improved, indicating that the traditional Chinese medicine eye patch of Example 2 of the present invention has a long action time for improving visual fatigue, can improve fatigue for a long time, and achieves the continuous effect of clearing heat and improving eyesight

[0232] Table 7 shows the comparison of visual fatigue scores before and after treatment with the traditional Chinese medicine eye patch prepared by the present invention

[0233] In the same area, 470 volunteers aged 15 - 80 years were recruited. These volunteers all had varying degrees of ocular visual fatigue symptoms. According to the order of filling in the questionnaire, these volunteers were divided into four groups: the comparative example group, the example group, a certain eye patch group, and the placebo group. The volunteers in the example group used the eye patch of this example, the certain eye patch group used a certain eye patch sold on the market, and the placebo group used clear water to simulate the traditional Chinese medicine eye patch for eye care, once a day, with a usage period of two weeks. They filled in the corresponding questionnaires before and after treatment respectively to record the improvement of the eyes. By the end of the study, a total of 55 volunteers did not have complete data, so they were excluded. Therefore, the final number of volunteers included in the statistics was: 120 cases in the comparative example group, 125 cases in the example group, 122 cases in the certain eye patch group, and 48 cases in the placebo group. The test data was entered and sorted through EXCEL 2020, and the data statistics was analyzed using SPSS22.0 software

[0234] Table 7 Visual fatigue symptom score table

[0235] Dry eyes No dryness sensation 0 points There is a slight dryness sensation 1 point The dryness sensation is relatively obvious and can be tolerated 2 points The dryness sensation is obvious and difficult to tolerate 3 points Eye swelling No eye swelling 0 points There is a slight swelling and sense of urgency in the eyes 1 point There is a relatively obvious swelling and sense of urgency in the eyes 2 points There is a relatively obvious swelling in the eyes and a dull pain in the supraorbital region 3 points Burning sensation No burning sensation 0 points Occasionally there is a burning sensation, which is generally not obvious 1 point The burning sensation is relatively obvious and slightly uncomfortable, and can be tolerated 2 points The burning sensation is obvious and feels uncomfortable, and is difficult to tolerate 3 points Photophobia No photophobia 0 points Slightly photophobic 1 point Moderate photophobia, unable to open eyes under sunlight 2 points Severe photophobia, difficult to open eyes 3 points Inability to sustain visual acuity Can sustain visual acuity for more than half an hour without discomfort 0 points Can sustain visual acuity for more than 15 - 20 minutes 1 point Can sustain visual acuity for 10 - 15 minutes 2 points Sustainable visual acuity for <10 minutes 3 points Blurred vision No blurred vision 0 points Mild blurred vision, but does not affect normal reading 1 point Moderate blurred vision, slightly affecting normal reading 2 points Severe blurred vision, seriously affecting normal reading 3 points

[0236] Table 8 is the visual fatigue symptom score table

[0237] Comparison of Visual Fatigue Scores before and after Treatment in Four Groups (Table 8)

[0238]

[0239] According to the results in Table 8, it can be seen that although the eye patch products in a certain eye patch group purchased on the market have a certain degree of improvement effect on visual fatigue symptoms, the products in the example group prepared by the present invention are more obvious in relieving visual fatigue symptoms and are easily accepted and recognized by the majority of consumers.

[0240] Conclusion: Through the verification of Comparative Example 2, the core innovation points of the present invention are as follows:

[0241] 1. Necessity of Compatibility: After removing traditional Chinese medicine compositions such as saffron and chuanxiong (Comparative Example 2), the tear film break-up time decreased from 14.1 ± 2.3 s to 9.7 ± 2.6 s (P < 0.01), proving that the compatibility of the five herbs is essential; 2. Technical Synergy: Ultrasonic-assisted deep eutectic solvent extraction increased the flavonoid yield by 2.7 times (Example 1 vs Comparative Example 1), which is directly related to a 71.4% increase in tear secretion.

[0242] 3. Clinical Advantage: Compared with commercially available eye patches (a certain brand), the onset time of the present invention was shortened by 40% (25.3 → 15.4 min, damp-heat syndrome type), and there was no skin irritation (rabbit skin irritation score 0 vs 1.2 for competing products).

[0243] The present invention has been described exemplarily in conjunction with the accompanying drawings. Obviously, the specific implementation of the present invention is not limited by the above methods. As long as various non-substantive improvements are made by adopting the method concept and technical solution of the present invention; or without improvement, the above concept and technical solution of the present invention are directly applied to other occasions, they are all within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for relieving dry eyes and visual fatigue, characterized in that: The raw materials of the traditional Chinese medicine composition are composed of 5-8 parts of saffron, 12-18 parts of wolfberry, 10-15 parts of chrysanthemum, 6-10 parts of cassia seed, 5-8 parts of buddlejac, 4-6 parts of ligusticum chuanxiong and 8-12 parts of glossy privet fruit by weight; the traditional Chinese medicine composition is prepared by first crushing the raw materials and then performing ultrasound-assisted deep eutectic solvent extraction.

2. A method for preparing a Chinese medicine composition for relieving dry eyes and visual fatigue, characterized in that: The following steps are involved: 1) Preparation of deep eutectic solvent: choline chloride, glycerol, lactic acid and water are mixed in a molar ratio of 1:2:2:2 to 1:5:6:6, and the mixture is placed in a water bath shaker at 45°C to 75°C and 300 to 1200 r / min to react for 0.5 to 2 hours to form a clear and transparent liquid. If no precipitation is formed after standing overnight, the deep eutectic solvent is successfully prepared and sealed for future use; 2) Grinding: Weigh 5-8 parts of saffron, 12-18 parts of wolfberry, 10-15 parts of chrysanthemum, 6-10 parts of cassia seed, 5-8 parts of buddlejac, 4-6 parts of ligusticum, and 8-12 parts of Ligustrum lucidum. Transfer to a wall-breaking machine for airflow grinding, adjust the temperature inside the machine to -10℃~20℃, introduce high-speed airflow, the airflow grinding pressure is 0.5~2.5MPa, and the grinding time is 2~5min to obtain a Chinese medicine composition powder; 3) Ultrasonic-assisted deep eutectic solvent extraction: pour the powder of the Chinese medicine composition into an ultrasonic container, and add a deep eutectic solvent with a mass ratio of 1:2 to 1:5 to the powder of the Chinese medicine composition, so that the powder of the Chinese medicine composition is completely immersed in the deep eutectic solvent; then ultrasonically treat with a power of 100 to 400 W, set the temperature to 35°C to 65°C, and the time is 30 to 120 min; then centrifuge at a speed of 2500 to 10000 rpm for 10 to 30 min, collect the supernatant and perform rotary evaporation concentration to obtain the Chinese medicine combination extract; 4) Freeze drying: The Chinese medicine combination extract obtained in step 3) is vacuum dried at -45°C to -55°C for 5 to 9 hours to obtain a Chinese medicine composition.

3. A method for preparing an eye protection essence for relieving dry eyes and visual fatigue, characterized in that: The following steps are involved: 1) Sodium hyaluronate, betaine, allantoin, xanthan gum, olefinic acid (esters) / C10-30 alkyl acrylate cross-linked polymer are sequentially added to an emulsifying pot, water is added, and the mixture is heated and stirred at 70°C to 95°C to dissolve, so that the mixture is fully dissolved to form an aqueous phase; after cooling to 35°C to 55°C, artificial musk, arginine, niacinamide, and panthenol are respectively added to the aqueous phase, and the mixture is sheared at high speed with a 3000-10000rpm high-speed shear homogenizer, and emulsified with 100-400W ultrasonic waves, the temperature is 35°C to 55°C, the working time is 5-10min, and the mixture is cooled in an ice water bath to obtain liquid A; 2) Take butanediol, add natural borneol and menthol, and stir with a stirrer until completely dissolved at a speed of 2000-5000 rpm for 5-10 min to obtain liquid B; 3) Take hydroxyacetophenone, 1,2-hexanediol and butanediol, heat and stir at 45°C to 55°C to dissolve, and obtain liquid C; 4) Add liquid B cooled to room temperature to liquid A in the emulsifying pot, and stir with a stirrer until completely mixed; then add the Chinese medicine composition as claimed in claim 1 and anthocyanins, and homogenize at a speed of 5000-12000 rpm, intermittently three times, each time for 10-30 seconds; heat the external circulation water temperature to 55°C-75°C, and sterilize for 15-35 minutes; finally add liquid C, stir evenly, and obtain a mixed liquid; 5) The pH value of the mixture is adjusted within the range of 6.0 to 6.5, the viscosity is adjusted within the range of 800 to 1200 mPa·s, and vacuum degassing is performed at 30° C. to 37° C. to finally form a light yellow, transparent, uniform liquid with a characteristic odor, which is the eye protection essence.

4. The method for preparing the eye protection essence for relieving dry eyes and visual fatigue according to claim 3, characterized in that: The components of the eye protection essence are as follows by weight: 2% to 7% of the Chinese medicine composition, 0.01% to 1% of anthocyanin, 0.01% to 1% of natural borneol, 0.01% to 1% of menthol, 0.01% to 1% of artificial musk, 0.05% to 0.1% of sodium hyaluronate, 0.5% to 1% of betaine, 0.05% to 0.2% of allantoin, 0.1% to 0.2% of xanthan gum, 1% to 6% of butylene glycol, 0.05% to 0.3% of olefinic acid (ester) / C10-30 alkyl acrylate cross-linked polymer, 0.05% to 0.3% of arginine, 0.05% to 0.1% of niacinamide, 0.05% to 0.1% of panthenol, 2.0% to 5.5% of preservatives, and the remaining amount of deionized water, distilled water or purified water; The preservative comprises 0.1% to 0.6% of p-hydroxyacetophenone, 0.1% to 0.5% of 1,2-hexanediol and 1.5% to 5% of butanediol.

5. An eye patch for relieving dry eyes and visual fatigue, characterized in that: The eye protection essence obtained in claim 3 or 4 is filled into an aluminum foil bag containing bamboo fiber non-woven fabric and sealed to obtain an eye patch.

6. An eye patch for relieving dry eyes and visual fatigue, characterized in that: Application in the treatment of dry eyes and visual fatigue.

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