Ligusticum wallichii stem and leaf eye patch and preparation method thereof

Abstract

The embodiment of the invention discloses a ligusticum wallichii stem and leaf eye patch and a preparation method thereof. The ligusticum wallichii stem and leaf eye patch is prepared from the following raw materials in parts by weight: 0.50 to 5.00 parts of medicinal components, 0.50 to 2.50 parts of xanthan gum, 0.50 to 4.00 parts of carrageenan, 0.5 to 1.5 parts of menthol, 2.00 to 20.00 parts of glycerol, 0 to 0.15 part of EDTA-2Na (Ethylene Diamine Tetraacetic Acid), 0 to 1.00 parts of potassium sorbate, 1.5 to 2.5 parts of Tween 80 and 100 parts of deionized water, the medicinal component consists of ligusticum wallichii freeze-dried powder, wolfberry-chrysanthemum freeze-dried powder and VE oil in a mass ratio of (1-3): (1-3): (1-3). The ligusticum wallichii stem and leaf eye patch provided by the invention has an excellent anti-oxidation effect and can effectively relieve eyestrain. Besides, the gel product is good in quality and stability, the variety of existing eye care products is enriched, development and utilization of ligusticum wallichii stem and leaf resources are achieved, and wide application prospects are achieved.

Description

Technical Field

[0001] The embodiments of the present invention relate to the technical field of eye care products, and particularly to a chuanxiong caulis et folium eye patch and a preparation method thereof. Background Art

[0002] With the increasing in-depth promotion of multimedia technology, the problems brought by visual fatigue will inevitably become more and more serious. Therefore, it is very necessary to find a preparation that can effectively treat eye fatigue and promote blood circulation in the eyes.

[0003] Chuanxiong caulis et folium was anciently called miwu. "Shennong Ben Cao Jing" records that it "mainly treats cough and counterflow, calms fright, expels evil, removes poisonous insects, ghosts and malaria, eliminates three kinds of worms, and long-term use makes one communicate with the divine." "Mingyi Bielu" records it as: "Mainly treats chronic wind in the body and chronic wind and dizziness in the head." "Lvchan Yan Ben Cao" also records it as: "Removes cold in the brain, treats floating wind on the face coming and going, lacrimation, excessive nasal discharge and various head winds. After eating, take the seedlings and chew them carefully, and send them down with tea." "Ben Cao Hui Yan" says: "Miwu is a medicine for treating head wind and dizziness. This medicine has a fragrant and clean smell, so it dispels wind and dampness." Miwu can also be eaten. In the Han Dynasty, there was "Going up the mountain to pick miwu, coming down the mountain to meet an old husband", in the Tang Dynasty, there was "Carrying a basket under the red leaves, spending the day picking miwu", in the Song Dynasty, there was "Miwu gradually covers the Chu Palace in green, and the grapes have not yet swelled in the Ba River slowly"... The application history of miwu is quite long. The long history of edible precedents and relatively high safety both indicate that the development and utilization of chuanxiong caulis et folium resources have relatively high value. At present, the research mainly focuses on the research of chuanxiong rhizome, and the research and utilization of the non-medicinal parts of the stems and leaves are very few. It is reported that most of the volatile oil components contained in miwu are the same as those in the rhizome, only the contents are different, and it has been reported that the phthalide content in its above-ground part is higher than that in the traditional medicinal part, the rhizome. And phthalide components can dilate blood vessels, promote blood circulation in the eyes, and effectively treat eye fatigue. Miwu is often used as a seasonal supply vegetable within a relatively small geographical area, and in addition, it can basically only be used as a fertilizer raw material, which causes a great waste of resources. The inventor's previous research found that the active ingredients of chuanxiong caulis et folium can dilate blood vessels and promote blood microcirculation. Therefore, developing an eye patch made of chuanxiong caulis et folium has important significance for enriching eye care products for relieving visual fatigue and realizing the development and utilization of chuanxiong caulis et folium resources. Summary of the Invention

[0004] Therefore, the embodiments of the present invention provide a chuanxiong caulis et folium eye patch and a preparation method thereof. The present invention uses freeze-dried powder of miwu in combination with chrysanthemum, wolfberry, cassia seed and vitamin E as the main components, supplemented with other medicinal excipients, to provide a chuanxiong caulis et folium eye patch with excellent antioxidant effect (referred to as miwu eye patch), which can effectively soothe eye fatigue. The present invention enriches the types of existing eye care products on the market, and at the same time realizes the development and utilization of chuanxiong caulis et folium resources, and has broad application prospects.

[0005] In order to achieve the above object, the embodiments of the present invention provide the following technical solutions:

[0006] According to the first aspect of the embodiments of the present invention, the present invention provides a Chuanxiong stem and leaf eye patch, which comprises the following raw materials in parts by weight: 0.50 - 5.00 parts of a medicinal effect component, 0.50 - 2.50 parts of xanthan gum, 0.50 - 4.00 parts of carrageenan, 0.5 - 1.5 parts of menthol, 2.00 - 20.00 parts of glycerol, 0 - 0.15 parts of EDTA-2Na, 0 - 1.00 parts of potassium sorbate, 1.5 - 2.5 parts of Tween 80, and 100 parts of deionized water; wherein, the medicinal effect component is composed of Asarum sieboldii Miq. freeze-dried powder, Lycium barbarum-Juemingzi freeze-dried powder, and VE oil with a mass ratio of 1 - 3:1 - 3:1 - 3.

[0007] Further, it comprises the following raw materials in parts by weight: 1.52 parts of a medicinal effect component, 1.99 parts of xanthan gum, 4.00 parts of carrageenan, 1.0 part of menthol, 15.00 parts of glycerol, 0.13 parts of EDTA-2Na, 0.75 parts of potassium sorbate, 2 parts of Tween 80, and 100 parts of water.

[0008] Further, the mass ratio of the Asarum sieboldii Miq. freeze-dried powder, Lycium barbarum-Juemingzi freeze-dried powder, and VE oil is 2∶3∶1.

[0009] Further, the preparation method of the Asarum sieboldii Miq. freeze-dried powder is as follows:

[0010] Mix fresh Asarum sieboldii Miq. with distilled water at a mass-to-volume ratio of 240:350 and make a pulp. Based on the mass of fresh Asarum sieboldii Miq., add 7% by mass of maltodextrin and 7% by mass of xylitol, stir evenly, and successively carry out pre-freezing and vacuum freeze-drying to obtain the Asarum sieboldii Miq. freeze-dried powder.

[0011] Further, the preparation method of the Lycium barbarum-Juemingzi freeze-dried powder is as follows:

[0012] Weigh wolfberry, chrysanthemum, and cassia seed in a mass ratio of 1∶2∶0.5, wash them, and dry them at 45 - 55 °C for later use;

[0013] Crush the cassia seed into a coarse powder of 20 - 40 meshes, add ethanol according to a solid-to-liquid ratio of 1∶6 - 10, soak overnight, then heat to boiling, keep it in a slightly boiling state for 1 - 2 h, filter to obtain a filtrate and cassia seed medicinal residues;

[0014] Mix the cassia seed medicinal residues with chrysanthemum and wolfberry, add ethanol according to a solid-to-liquid ratio of 1∶8 - 12, soak for 2 - 4 h, decoct for 0.5 - 1.5 h, filter, combine the two filtrates, concentrate under reduced pressure to a solid content of 55% ± 0.5%, and carry out vacuum freeze-drying to obtain the Lycium barbarum-Juemingzi freeze-dried powder.

[0015] According to the second aspect of the embodiments of the present invention, the present invention provides a preparation method of the Chuanxiong stem and leaf eye patch as described in any one of the above, and the method comprises the following steps:

[0016] (1) Mix xanthan gum, chondrus ocellatus holmes, menthol, glycerol and a portion of deionized water to obtain Solution A;

[0017] (2) Mix EDTA-2Na, potassium sorbate, Tween 80, the pharmaceutically active ingredient and the remaining deionized water to obtain Solution B;

[0018] (3) Mix Solution A and Solution B, heat, then place in a mold and fully swell under low temperature conditions to obtain the Ligusticum wallichii stem and leaf eye patch.

[0019] Further, in step (1), based on the mass of deionized water, the mass proportion of the portion of deionized water is 40 - 60%.

[0020] Further, in step (3), the heating conditions are: 80 - 95 °C, 1 - 2 h.

[0021] Further, in step (3), the low temperature conditions are: 0 - 4 °C, 10 - 15 h.

[0022] The embodiments of the present invention have the following advantages:

[0023] The present invention takes adhesion, elasticity, cohesiveness, resilience and skin moisture content, etc. as evaluation indexes, conducts a large number of screenings on the types and contents of the pharmaceutically active ingredient and excipients, optimizes the important components affecting the properties of the apium graveolens var. dulce eye patch by the response surface method, and simultaneously investigates the quality and stability of the eye patch. The Ligusticum wallichii stem and leaf eye patch provided by the present invention has excellent antioxidant efficacy and can effectively relieve eye fatigue. In addition, the quality and stability of the gel product are good. The present invention enriches the types of existing eye care products on the market, realizes the development and utilization of Ligusticum wallichii stem and leaf resources, and has broad application prospects. Description of the Drawings

[0024] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only exemplary, and for those of ordinary skill in the art, without creative efforts, other implementation drawings can also be obtained according to the provided drawings.

[0025] Figure 1 It is the skin moisture content result of the screening of the gel matrix types provided by the present invention;

[0026] Figure 2 It is the gel matrix type screening product provided by the present invention;

[0027] Figure 3 It is the skin moisture content result of the screening of the matrix content provided by the present invention;

[0028] Figure 4 Skin moisture content results of film-forming agent type screening provided by the present invention;

[0029] Figure 5 Product of film-forming agent type screening provided by the present invention;

[0030] Figure 6 Skin moisture content results of film-forming agent content screening provided by the present invention;

[0031] Figure 7 Skin moisture content results of humectant content screening provided by the present invention;

[0032] Figure 8 Skin moisture content results of antioxidant content screening provided by the present invention;

[0033] Figure 9 Skin moisture content results of preservative content screening provided by the present invention;

[0034] Figure 10 Skin moisture content results of active ingredient content screening provided by the present invention;

[0035] Figure 11 Three-dimensional response diagram of the mutual relationship of various factors and standardized scores provided by the present invention;

[0036] Figure 12 Skin moisture content of the final product provided by the present invention. Detailed implementation manners

[0037] The following specific embodiments illustrate the implementation manners of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of them. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0038] Example 1

[0039] 1. Materials and instruments

[0040] 1.1 Materials and reagents

[0041] Table 1 Main materials and reagents

[0042]

[0043]

[0044] 1.2 Instruments and equipment

[0045] Table 2 Main instruments and equipment

[0046]

[0047] 2. Experimental methods

[0048] 2.1 Analysis of the eye patch prescription

[0049] The freeze-dried powder of Heracleum scabridum, wolfberries, chrysanthemums, the freeze-dried powder of the water extract of cassia seeds, and VE oil are used as the main drug components of the Heracleum scabridum eye patch prescription. Among them, the freeze-dried powder of Heracleum scabridum was prepared by the research group through vacuum freeze-drying (VFD) in the early stage. The preparation method is as follows: Add 240 g of fresh Heracleum scabridum to 350 mL of distilled water to prepare a pulp (100 r / min, 3 min), add freeze-drying protectants (maltodextrin and xylitol, each 7% of the weight of fresh Heracleum scabridum), stir evenly (100 r / min, 2 min), perform pre-freezing treatment at -60°C for 5 h, and then perform vacuum freeze-drying. The conditions for vacuum freeze-drying are: vacuum degree ≤ 10 Pa, time 28 h. After completion, powder is obtained by pulverizing with a pulverizer to get the freeze-dried powder of Heracleum scabridum. The gel matrix is screened from xanthan gum and carbomer. The film-forming agent is screened from carrageenan, hydroxyethyl cellulose, and Vigna sesquipedalis gum. Menthol, glycerol, deionized water, EDTA-2Na, potassium sorbate, and Tween 80 are used as penetration enhancer, humectant, solvent, antioxidant, preservative, and co-solvent respectively.

[0050] 2.2 Preparation of the freeze-dried powder of the water extract of wolfberries, chrysanthemums, and cassia seeds

[0051] Weigh wolfberries, chrysanthemums, and cassia seeds with a mass ratio of 1:2:0.5. After washing, dry them at a low temperature of 50°C respectively. The cassia seeds are pulverized into coarse powder with a mesh size of 20 - 40. For the cassia seed powder, use ethanol as the solvent with a material-liquid ratio of 1:8, soak overnight, heat with an electric heating mantle until boiling, and then keep it in a slightly boiling state for 2 h, and filter. For the cassia seed residue + chrysanthemums + wolfberries, use ethanol as the solvent with a material-liquid ratio of 1:10, soak for 4 h, decoct for 1 h, filter, and combine the two filtrates, and concentrate under reduced pressure to a solid content of 55% ± 0.5%. Then, the concentrated solution after concentration is subjected to vacuum freeze-drying to obtain the freeze-dried powder of the water extract of wolfberries, chrysanthemums, and cassia seeds (referred to as the freeze-dried powder of wolfberries, chrysanthemums, and cassia seeds).

[0052] 2.3 Investigation of the proportion of pharmacodynamic components

[0053] This study uses freeze-dried powder of Heracleum scabridum, freeze-dried powder of Lycium barbarum and chrysanthemum with Cassia obtusifolia, and VE oil as the main medicinal components. In order to further determine the proportion of each medicinal component, an orthogonal experiment with three factors and three levels (L933) was adopted, in which three levels of proportioning of three factors, namely freeze-dried powder of Heracleum scabridum (A), freeze-dried powder of Lycium barbarum and chrysanthemum with Cassia obtusifolia (B), and VE oil (C), were 1 part, 2 parts and 3 parts respectively. The configuration ratios of each sample number are shown in Table 3, and the antioxidant activities of the medicinal components with different ratios were investigated according to the method under "2.6".

[0054] Table 3 Investigation on the optimal ratio of medicinal components

[0055]

[0056] 2.4 Single-factor investigation of gel

[0057] 2.4.1 Screening of gel matrix types

[0058] The gel matrices to be screened this time are carbomer and xanthan gum. Different preparation schemes were designed for different gel matrices.

[0059] (1) Preparation of carbomer gel matrix:

[0060] Precisely weigh 1.5 g of carbomer (gel matrix), sprinkle it evenly in portions on the water surface (take 30% of the total amount, 30 mL), let it stand overnight, and fully swell. Then adjust the pH to 2 - 3 with ascorbic acid, add 0.10 g of EDTA-2Na (antioxidant), 0.75 g of potassium sorbate (preservative), 2 g of Tween 80 (cosolvent) and the medicinal components (when screening the gel matrix type, the dosage of the medicinal components is 0) to obtain Solution A; dissolve 4 g of carrageenan (film-forming agent) and 1 g of menthol (penetration enhancer) with 15 g of glycerol (humectant) to obtain Solution B; slowly add Solution B to Solution A, stir in the same direction, add water to the total amount (100 mL), adjust the pH to 6 - 8 with triethanolamine, stir evenly, place the stirred gel in a water bath at 90 °C, heat

[0061] for 1.5 h, take it out, place it in a mold, and fully swell it overnight in the refrigerator (4 °C, 12 h) to obtain the carbomer gel matrix.

[0062] (2) Preparation of xanthan gum gel matrix:

[0063] Accurately weigh 1.5 g of xanthan gum (gel matrix), 4 g of carrageenan (film-forming agent), and 1 g of menthol (penetration enhancer) and place them in a 100 mL beaker. After adding 15 g of glycerol (humectant) and stirring to moisten, add 50 mL of deionized water while stirring, and record the stirred liquid as Solution A; dissolve 0.10 g of EDTA-2Na (antioxidant), 0.75 g of potassium sorbate (preservative), 2 g of Tween 80 (cosolvent), and the active ingredient (when screening the gel matrix type, the dosage of the active ingredient is 0) in 50 mL of deionized water, mix well, and record the resulting liquid as Solution B; mix Solutions A and B, place them in a water bath at 90 °C, heat for 1.5 h, take out, place in a mold, and fully swell overnight in the refrigerator (4 °C, 12 h) to obtain the xanthan gum gel matrix.

[0064] 2.4.2 Screening of gel matrix content

[0065] Parallelly prepare 5 gel patches according to the gel preparation method under "2.4.1", and the dosages of the gel matrix are 0.50 g, 1.00 g, 1.50 g, 2.00 g, and 2.50 g respectively. The dosage of deionized water for each gel patch is 100 mL.

[0066] Similarly, according to the screening method under "2.4.9", compare the standardized scores, skin water content, and formability to screen out the appropriate gel matrix content.

[0067] 2.4.3 Screening of film-forming agent type

[0068] Parallelly prepare 3 gel patches (without active ingredient) according to the method under "2.4.1", and the types of film-forming agents used are locust bean gum, hydroxyethyl cellulose, and carrageenan respectively. The dosage of deionized water for each gel patch is 100 mL.

[0069] Similarly, according to the screening method under "2.4.9", compare the standardized scores, skin water content, and formability to screen out the appropriate type of film-forming agent.

[0070] 2.4.4 Screening of film-forming agent content

[0071] Parallelly prepare 5 gel patches according to the method under "2.4.1", and the film-forming agent contents are 0.50 g, 1.00 g, 2.00 g, 3.00 g, and 4.00 g respectively. The dosage of deionized water for each gel patch is 100 mL.

[0072] Similarly, according to the screening method under "2.4.9", compare the standardized scores, skin water content, and formability to screen out the appropriate film-forming agent content.

[0073] 2.4.5 Screening of humectant content

[0074] Prepare 5 gel patches in parallel according to the gel preparation method under "2.4.1", with the humectant contents being 2.00 g, 5.00 g, 10.00 g, 15.00 g, and 20.00 g respectively. The amount of deionized water used for each gel patch is 100 mL.

[0075] Similarly, according to the screening method under "2.4.9", compare the standardized scores, skin water content, and formability to screen out the appropriate humectant content.

[0076] 2.4.6 Screening of antioxidant content

[0077] Prepare 5 gel patches in parallel according to the gel preparation method under "2.4.1", with the antioxidant contents being 0.00 g, 0.02 g, 0.05 g, 0.10 g, and 0.15 g respectively. The amount of deionized water used for each gel patch is 100 mL.

[0078] Similarly, according to the screening method under "2.4.9", compare the standardized scores, skin water content, and formability, and also examine the pH value of the gel when different amounts of antioxidants are used to screen out the appropriate antioxidant content.

[0079] 2.4.7 Screening of preservative content

[0080] Prepare 5 gel patches in parallel according to the gel preparation method under "2.4.1", with the preservative contents being 0.00 g, 0.25 g, 0.50 g, 0.75 g, and 1.00 g respectively. The amount of deionized water used for each gel patch is 100 mL.

[0081] Similarly, according to the screening method under "2.4.9", compare the standardized scores, skin water content, and formability, and also examine the mildew situation of the gel when different amounts of preservatives are used to screen out the appropriate preservative content.

[0082] 2.4.8 Investigation of active ingredient content

[0083] Prepare 5 gel patches in parallel according to the gel preparation method under "2.4.1", with the active ingredient contents being 0.50 g, 1.00 g, 1.50 g, 2.00 g, 3.00 g, and 5.00 g respectively. The amount of deionized water used for each gel patch is 100 mL.

[0084] Similarly, according to the screening method under "2.4.9", compare the standardized scores, skin water content, and formability.

[0085] 2.4.9 Scoring criteria and calculation

[0086] (1) Texture analyzer measurement

[0087] The adhesiveness, elasticity, cohesiveness and resilience of the gel eye patches were measured using a food texture analyzer.

[0088] Table 4 Interpretation of the data measured by the texture analyzer

[0089]

[0090] (2) Standardized score

[0091] The data of adhesiveness, elasticity, cohesiveness and resilience in the results measured by the texture analyzer were normalized by the range method. The standardized scores of the gel eye patches with different formulations were calculated according to the following formula, namely:

[0092] X = S1 + S2 + S3 + S4 (1)

[0093] In the formula:

[0094] X —— The standardized score of the gel eye patch;

[0095] S1 —— The range-normalized score of the adhesiveness of the gel eye patch;

[0096] S2 —— The range-normalized score of the elasticity of the gel eye patch;

[0097] S3 —— The range-normalized score of the cohesiveness of the gel eye patch;

[0098] S4 —— The range-normalized score of the resilience of the gel eye patch.

[0099] (3) Gel eye patch formability standard

[0100] Observe the state of the gel formed in the mold. It is appropriate that the viscosity is appropriate, plump and shiny.

[0101] (4) Skin water content measurement method

[0102] The skin water content measured by a skin tester at 0, 5, 10, 15, and 30 minutes after removing the patch that has been applied to the skin surface for 10 minutes.

[0103] (5) Mildew determination method and standard

[0104] The product was stored at room temperature and in an environment of (5 ± 1) °C for 48 hours, and whether mildew or colonies were generated on the gel was observed.

[0105] (6) Gel eye patch stability standard

[0106] The product was kept for one week in an environment of room temperature, (5 ± 1) °C, (40 ± 1) °C, cycling between (5 ± 1) °C and (40 ± 1) °C. The appearance, odor, pH and adhesiveness of the four groups of gel eye patches were observed every day.

[0107] 2.5 Process Optimization of Miwu Eye Patches

[0108] According to the results of the above single-factor experiments and the correlation analysis between each factor and the standardized score of the gel, the factors with greater influence, namely the content of the active ingredient (A), the content of the antioxidant (B), and the content of the gel matrix (C), were selected for process optimization. An experimental design with 3 factors and 3 levels was adopted, as shown in Table 5. The response value (R1) for model fitting and variance analysis was taken as 50% of the standardized score + 50% of the sensory score. The detailed rules for sensory evaluation are shown in Table 6. The Box-Behnken test was established using Design-Expert software. And the obtained results were verified and compared accordingly to judge the advantages and reliability of the preparation process.

[0109] Table 5 Factor-Level Table for Box-Behnken Design

[0110]

[0111] Table 6 Sensory Evaluation Criteria

[0112]

[0113] 2.6 Research on Antioxidant Activity

[0114] Preparation of ABTS solution: Weigh ABTS and potassium persulfate powders, dissolve them in absolute ethanol, and prepare solutions with concentrations of 7.0 mmol / L and 2.45 mmol / L respectively. Mix the two solutions in equal volumes, react in the dark for 16 h, adjust the absorbance of the reaction solution to about 0.7 with absolute ethanol, and store it at 4 °C for later use.

[0115] Preparation of DPPH solution: Weigh DPPH powder, dissolve it in absolute ethanol to prepare a solution with a concentration of 0.1 mmol / L, and store it at -20 °C for later use.

[0116] Preparation of sample solution: Take 1.0 g of the sample, weigh it precisely, place it in a 50 mL centrifuge tube, add 25 mL of methanol, shake well, ultrasonically extract for 30 min at room temperature, centrifuge at 12000 rpm for 10 min, and take the supernatant to obtain the sample solution.

[0117] DPPH· radical scavenging ability: Take 50 μL of sample solutions with different concentrations and mix them with 250 μL of DPPH solution respectively, and incubate in the dark at room temperature for 30 min. After the reaction, use a microplate reader to detect the absorbance of the reaction solution at 517 nm. Use methanol instead of the sample solution as the negative control, and absolute ethanol instead of the DPPH solution as the sample background. Each sample is measured in parallel three times.

[0118] ABTS +· Radical scavenging ability: 50 μL of sample solutions with different concentrations were respectively mixed with 250 μL of ABTS solution, and the reaction was carried out in the dark at room temperature for 6 min. After the reaction, the absorbance of the reaction solution at 734 nm was measured with an enzyme-linked immunosorbent assay (ELISA) reader. The negative control and sample background were set in the same way as the determination of DPPH radical scavenging activity. Each sample was measured in parallel three times. The calculation formulas for the DPPH and ABTS radical scavenging rates are as follows:

[0119] Scavenging rate of DPPH / ABTS (%) = [1 - (Ae - As) / Ac] × 100% (2)

[0120] In the formula:

[0121] Ae——Absorbance of the reaction solution;

[0122] Ac——Absorbance of the negative control;

[0123] As——Absorbance of the sample background.

[0124] 2.7 Quality inspection of Miwu eye patches

[0125] According to the method under "2.4.9", the adhesiveness, elasticity, cohesiveness and resilience, skin water content and stability of the gel eye patches after screening the prescription were inspected.

[0126] 3. Results and discussion

[0127] 3.1 Results of investigation on the proportion of pharmacodynamic components

[0128] There is a close relationship between antioxidant activity and relieving eye fatigue. The higher the antioxidant activity of the pharmacodynamic components, the better the performance of relieving eye fatigue usually is. Antioxidant components can relieve eye fatigue by scavenging free radicals, protecting cells, anti-inflammatory and promoting blood circulation, etc., by relieving oxidative stress in the eyes, protecting eye cells, promoting blood circulation and nutrient supply. Therefore, in the present invention, the proportion of pharmacodynamic components was screened by investigating the antioxidant activity of the pharmacodynamic components.

[0129] The investigation results are shown in Table 7 and Table 8. From the results in the tables, it can be known that in the DPPH orthogonal experiment, when the mass ratio of Miwu freeze-dried powder, Qiju Jue freeze-dried powder, and VE oil is 1:2:2, the scavenging rate is the highest, reaching 57.35%. In the ABTS orthogonal experiment, when the mass ratio of Miwu freeze-dried powder, Qiju Jue freeze-dried powder, and VE oil is 2:3:1, the scavenging rate is the highest, reaching 74.35%. Considering the two experiments comprehensively, it is preliminarily judged that the optimal mass ratio of the antioxidant activity of the active components of Miwu eye patches is: Miwu freeze-dried powder:Qiju Jue freeze-dried powder:VE oil = 2:3:1.

[0130] Table 7 DPPH experiments with different proportions of pharmacodynamic components

[0131]

[0132] Table 8 ABTS experiment with different ratios of active ingredients

[0133]

[0134] 3.2 Results of single-factor investigation of gels

[0135] 3.2.1 Results of screening of gel matrix types

[0136] As shown in the data in Table 9, the adhesiveness, elasticity, cohesiveness, and standardized scores of the gel matrix made with carbomer as the matrix and the gel made with xanthan gum as the matrix are not very different. The xanthan gum gel has a higher resilience. According to Figure 1 it can be seen that there is no significant difference in the standardized scores and the final skin water content of the two gels (P > 0.05). However, from Figure 2 it can be seen that the gel matrix made with carbomer as the matrix has poor molding. Therefore, xanthan gum was selected as the gel matrix for the follow-up.

[0137] Table 9 Results of screening of gel matrix types

[0138]

[0139] 3.2.2 Results of screening of matrix content

[0140] Xanthan gum was selected as the gel matrix to investigate the effect of different amounts of gel matrix on the gel properties.

[0141] As shown in the data in Table 10, when the xanthan gum content is 1.5 g, the gel made has the highest adhesiveness, elasticity, and cohesiveness, and the lowest resilience. The standardized score is the highest, at 3.00. According to Figure 3 it can be seen that when the xanthan gum content is 0.5 g, the final skin water content is the highest. When the content is at other levels, the final skin water content of the gel is not very different (P > 0.05). Therefore, the amount of xanthan gum selected is 1.5 g.

[0142] Table 10 Results of screening of matrix content

[0143]

[0144] 3.2.3 Results of screening of film-forming agent types

[0145] 1.5 g of xanthan gum was selected as the gel matrix to investigate the effect of different types of film-forming properties on the gel properties.

[0146] As shown in Table 11, the gel made with carrageenan as the film-forming agent has relatively high adhesiveness, the highest elasticity, relatively low cohesiveness and resilience, and the highest standardized score, at 2.24. According to Figure 4It can be seen that the final skin water content of the gels made from the three film-forming agents is not significantly different (P > 0.05), and as can be seen from Figure 5 it, the clarity and formability of the gel made from carrageenan are better, so carrageenan is selected as the film-forming agent.

[0147] Table 11 Screening results of film-forming agent types

[0148]

[0149] 3.2.4 Screening results of film-forming agent content

[0150] 1.5 g of xanthan gum was selected as the gel matrix and carrageenan as the film-forming agent to investigate the effect of different carrageenan contents on the gel properties.

[0151] As shown in Table 12, when the amount of carrageenan is 4.0 g, the gel prepared has higher elasticity, the highest cohesiveness, lower resilience, and the highest standardized score of 3.17. According to Figure 6 it can be seen that the final skin water content is higher than that of the gels with other carrageenan contents, so the amount of carrageenan is selected as 4.0 g.

[0152] Table 12 Screening results of film-forming agent content

[0153]

[0154] 3.2.5 Screening of humectant content

[0155] 1.5 g of xanthan gum was selected as the gel matrix, 4.0 g of carrageenan as the film-forming agent, and the effect of different glycerol contents on the gel properties was investigated.

[0156] As shown in Table 13, when the amount of glycerol is 15.00 g, the gel prepared has lower adhesiveness, higher elasticity, cohesiveness, and resilience, and the highest standardized score of 2.53. According to Figure 7 it can be seen that the final skin water content of the gel is not significantly different from that of other gels (P > 0.05), so the amount of glycerol is selected as 15.00 g.

[0157] Table 13 Screening of humectant content

[0158]

[0159]

[0160] 3.2.6 Screening results of antioxidant content

[0161] 1.5 g of xanthan gum was selected as the gel matrix, 4.0 g of carrageenan as the film-forming agent, and 15.00 g of glycerol as the humectant to investigate the effect of different EDTA-2Na contents on the gel properties.

[0162] As shown in Table 14, when the dosage of EDTA-2Na is 0.10 g, the gel prepared has relatively high adhesiveness, elasticity, and cohesiveness, relatively high resilience, and the highest standardized score of 3.18. According to Figure 8 it can be seen that its final skin moisture content is relatively high compared with other gels. From Table 15, it can be seen that the pH of the gel is 7.87 when the dosage of EDTA-2Na is 0.10 g. Considering that the optimal pH for ophthalmic preparations is 5 - 9, within the applicable range of ophthalmic preparations, the dosage of EDTA-2Na is therefore selected as 0.10 g.

[0163] Table 14 Screening Results of Antioxidant Content

[0164]

[0165] Table 15 Gel pH Values with Different Antioxidant Dosages

[0166]

[0167] 3.2.7 Screening Results of Preservative Content

[0168] 1.5 g of xanthan gum was selected as the gel matrix, 4.0 g of carrageenan as the film-forming agent, 15.00 g of glycerol as the humectant, and 0.1 g of EDTA-2Na as the antioxidant to investigate the effect of different potassium sorbate contents on the gel properties.

[0169] As shown in Table 16, although the standardized score is higher when the dosage of potassium sorbate is 0.25 g than when it is 0.75 g, according to Figure 9 it can be seen that when the dosage of potassium sorbate is 0.75 g, the final skin moisture content is higher and the moisturizing property is better. From Table 17, it can be seen that the mildew situation of gels with different preservative contents is the same. Therefore, the dosage of potassium sorbate is selected as 0.75 g.

[0170] Table 16 Screening Results of Preservative Content

[0171]

[0172] Table 17 Mildew Situation

[0173]

[0174] 3.2.8 Screening Results of Active Ingredient Content

[0175] 1.5 g of xanthan gum was selected as the gel matrix, 4.0 g of carrageenan as the film-forming agent, 15.00 g of glycerol as the humectant, 0.1 g of EDTA-2Na as the antioxidant, and 0.75 g of potassium sorbate as the preservative. The effects of different contents of active pharmaceutical ingredients (the mass ratio of Asarum sieboldii Miq. freeze-dried powder: Chrysanthemum morifolium Ramat. and Cynomorium songaricum Rupr. freeze-dried powder: VE oil was 2:3:1) on the gel properties were investigated.

[0176] As shown in Table 18, when the dosage of the active pharmaceutical ingredient was 2.0 g, the prepared gel had relatively high adhesiveness, elasticity, cohesiveness, and resilience, and the standardized score was the highest, which was 3.39. And according to Figure 10 it was known that its skin water content at 30 min was the highest among other gels. Therefore, the dosage of the active pharmaceutical ingredient was selected as 2.0 g.

[0177] Table 18 Screening results of the content of active pharmaceutical ingredients

[0178]

[0179]

[0180] 3.3 Results of process optimization

[0181] The Box-Behnken experimental design and results are shown in Table 19.

[0182] Table 19 Box-Behnken experimental design and results

[0183]

[0184] As can be seen from Table 20, it indicated that the experimental model had a very high significance (F value = 8.00, P = 0.0060), and the equation fitted well with the actual situation. The F value of the lack-of-fit term was 3.03, P = 0.1558, indicating that the lack-of-fit term was not significant and the unknown factors had little interference on the test results. The effects of the three factors were relatively obvious (P < 0.2), and the significance order of the factors affecting the gel preparation was antioxidant content > active pharmaceutical ingredient content > gel matrix content. The correlation coefficient R2 of the model was 0.9114. Therefore, this model equation was used to reasonably analyze the experimental results of the prepared gel patches.

[0185] Table 20 Variance analysis of the regression model

[0186]

[0187]

[0188] Response surface was used to optimize and predict it. Using DesignExpert software, based on the binomial fitting model, one of the three variables was fixed, and the three-dimensional response surface of the influence of the other two variables on the standardized score was drawn. The results are shown in Figure 11 .

[0189] After software analysis and screening, the optimal preparation process parameters of the gel were obtained as follows: the content of the active ingredient was 1.52%, the content of the antioxidant was 0.13%, the content of the gel matrix was 1.99%, and the 50% standardized score + 50% sensory score of the gel patch was predicted to be 68.94.

[0190] 3.4 Quality inspection results

[0191] According to the screening results, a gel patch is provided, and its preparation method is as follows:

[0192] Place 1.99 g of xanthan gum, 4 g of carrageenan and 1 g of menthol in a beaker, add 15 g of glycerol, wet and stir, then add 50 mL of deionized water while stirring, and record the stirred liquid as liquid A; dissolve 0.13 g of EDTA-2Na, 0.75 g of potassium sorbate, 2 g of Tween 80 and 1.52 g of the active ingredient (a mixture of dry powder of Heracleum dissectum, dry powder of Lycium barbarum and chrysanthemum, and VE oil in a mass ratio of 2:3:1) in 50 mL of deionized water, mix well, and record the resulting liquid as liquid B; mix liquids A and B, place them in a water bath at 90 °C, heat for 1.5 h, take out, place in a mold, and fully swell overnight in the refrigerator (4 °C, 12 h) to obtain the final product.

[0193] The quality inspection results are shown in Table 21 and Figure 12 As shown, the adhesiveness of the final product is -77.12 gf*s, the elasticity is 0.96, the cohesiveness is 0.33, and the resilience is 0.47; the water content of the skin after applying the eye patch basically remains at about 46%; the investigation of stability is mainly to confirm whether the appearance, odor, pH, etc. of the product will change under various different conditions and significantly exceed the initial performance of the product. The test results of stability are shown in Table 22, and the appearance, odor and pH value of the product are all stable within the normal range. Based on this, it is judged that the product has a certain stability.

[0194] Table 21 Characteristics of the final product

[0195]

[0196] Table 22 Test results of stability

[0197]

[0198] The following efficacy tests were carried out on the gel patch provided under "3.4":

[0199] General information: 40 volunteers, aged 18 - 60 years old, regardless of gender. Inclusion criteria: The duration of daily exposure to video terminals is not less than 5 hours, and there are obvious eye fatigue symptoms, such as dryness, swelling pain, soreness, etc. Exclude those with severe eye diseases; those allergic to the ingredients of the eye patch; and those who have used other eye care products recently (within the recent 2 weeks).

[0200] Usage method: Volunteers use the eye patch once every night before going to bed. Each time, apply the eye patch on the eyes for 15 - 30 minutes and use it continuously for 2 weeks.

[0201] Efficacy judgment: Volunteers subjectively score their own symptoms of eye dryness, swelling pain, fatigue, etc., with the scoring range being 0 - 10 points. At the same time, record in detail the feelings during the use of the eye patch and whether any adverse reactions occur. The efficacy judgment criteria are divided into the following three categories:

[0202] Effective: Symptoms such as eye dryness, swelling pain, and fatigue completely disappear, and the eye function of the patient recovers well. General: Symptoms such as eye dryness, swelling pain, and fatigue are significantly improved, and the recovery degree of the patient's eye function is average. Ineffective: Symptoms such as eye dryness, swelling pain, and fatigue are not significantly improved, and the recovery of the patient's eye function is poor.

[0203] Results: After statistics, among the 40 volunteers, 20 were effective, 18 were general, and 2 were ineffective. The total effective rate was 95%. The research results show that the eye patch has a significant effect in relieving symptoms such as eye dryness, swelling pain, and fatigue of patients, can better soothe eye fatigue, and promote the recovery of the eye function of patients. In addition, during the entire research process, no obvious adverse reactions occurred in all subjects, indicating that the eye patch has good safety.

[0204] Although the present invention has been described in detail with general descriptions and specific embodiments above, based on the present invention, some modifications or improvements can be made, which are obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection required by the present invention.

Claims

1. A chuanxiong stem and leaf eye patch, characterized in that: The invention comprises the following raw materials in parts by weight: 0.50-5.00 parts of medicinal ingredients, 0.50-2.50 parts of xanthan gum, 0.50-4.00 parts of carrageenan, 0.5-1.5 parts of menthol, 2.00-20.00 parts of glycerol, 0-0.15 parts of EDTA-2Na, 0-1.00 parts of potassium sorbate, 1.5-2.5 parts of Tween 80, and 100 parts of deionized water; wherein the medicinal ingredients are composed of freeze-dried powder of Miwu, freeze-dried powder of Qijujue and VE oil in a mass ratio of 1-3:1-3:1-3.

2. The Chuanxiong stem and leaf eye patch according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 1.52 parts of medicinal ingredients, 1.99 parts of xanthan gum, 4.00 parts of carrageenan, 1.0 parts of menthol, 15.00 parts of glycerol, 0.13 parts of EDTA-2Na, 0.75 parts of potassium sorbate, 2 parts of Tween 80 and 100 parts of water.

3. The Chuanxiong stem and leaf eye patch according to claim 1, characterized in that: The mass ratio of the miwu lyophilized powder, the qijujue lyophilized powder and the VE oil is 2:3:

1.

4. The Chuanxiong stem and leaf eye patch according to claim 1, characterized in that: The preparation method of the lyophilized powder of Rhizoma Cibotii is as follows: Fresh mugwort and distilled water in a mass volume ratio of 240:350 are mixed and beaten, and 7% of maltodextrin and 7% of xylitol are added based on the mass of the fresh mugwort, and stirred evenly, and pre-frozen and vacuum freeze-dried in sequence to obtain the mugwort freeze-dried powder.

5. The Chuanxiong stem and leaf eye patch according to claim 1, characterized in that: The preparation method of the Qijujue freeze-dried powder is as follows: Weigh wolfberry, chrysanthemum and cassia seed in a mass ratio of 1:2:0.5, wash and dry them at 45-55°C for later use; Crush Cassiae Seed into 20-40 mesh coarse powder, add ethanol at a solid-liquid ratio of 1:6-10, soak overnight, heat to boiling, keep the slightly boiling state for 1-2 hours, filter, and obtain filtrate and Cassiae Seed residue; The cassia seed residue is mixed with chrysanthemum and wolfberry, and ethanol is added at a solid-liquid ratio of 1:8-12, soaked for 2-4 hours, decocted for 0.5-1.5 hours, filtered, the two filtrates are combined, concentrated under reduced pressure to a solid content of 55%±0.5%, and vacuum freeze-dried to obtain the cassia seed freeze-dried powder.

6. The method for preparing the Chuanxiong stem and leaf eye patch according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: (1) Mix xanthan gum, betaine, menthol, glycerin and part of deionized water to obtain liquid A; (2) mixing EDTA-2Na, potassium sorbate, Tween 80, the active ingredient and the remainder of deionized water to obtain solution B; (3) Liquid A and Liquid B are mixed, heated, and then placed in a mold to fully swell under low temperature conditions to obtain the Chuanxiong stem and leaf eye patch.

7. The method for preparing the Chuanxiong stem and leaf eye patch according to claim 6, characterized in that: In step (1), based on the mass of deionized water, the mass of the partial deionized water accounts for 40-60%.

8. The method for preparing the Chuanxiong stem and leaf eye patch according to claim 6, characterized in that: In step (3), the heating conditions are: 80-95° C., 1-2 h.

9. The method for preparing the Chuanxiong stem and leaf eye patch according to claim 6, characterized in that: In step (3), the low temperature condition is: 0-4°C, 10-15h.

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