A water gel material containing guaiazulene, its preparation method and application

Abstract

This invention discloses a hydrocolloid material containing guaiac, its preparation method, and its application, belonging to the field of medical care materials technology. It includes a backing layer and a hydrocolloid functional layer. The hydrophobic elastomer matrix comprises polyisobutylene, styrene-isoprene-styrene block copolymer, tackifying resin, liquid paraffin, and optionally caprylic / capric triglycerides. The pre-wetted hydrophilic absorbent powder comprises sodium carboxymethyl cellulose, pectin, gelatin, calcium alginate, sodium alginate, and caprylic / capric triglycerides. The composite plant repair oil comprises a phellodendron amurense lipid dispersion, Lithospermum erythrorhizon-Angelica dahurica extract, borage oil, sandalwood seed oil, borneol, and DL-α-tocopherol. The guaiac nanoliposome lyophilized powder is obtained by sequentially coating a guaiac nanoliposome aqueous dispersion with quaternized chitosan and sodium hyaluronate, then adding a lyophilization protectant and freeze-drying. This invention solves the problems of poor dispersion stability, easy degradation, insufficient soothing and repairing ability of guaiac, and instability in oil-water blends.

Description

Technical Field

[0001] This invention belongs to the field of medical care materials technology, specifically relating to a hydrocolloid material containing guaiac, its preparation method, and its application. Background Technology

[0002] Hydrocolloid dressings are a commonly used type of moist wound care material, typically composed of a hydrophobic elastomer matrix and a hydrophilic absorbent gel component. Upon contact with wound exudate, the hydrophilic component absorbs the exudate and forms a gel layer, thereby maintaining a moist environment and reducing direct adhesion between the dressing and the wound. However, ordinary hydrocolloid dressings mainly rely on absorbent gel formation and physical coverage. In scenarios with significant inflammation, pain sensitivity, unstable wound microenvironment, or easy adhesion during dressing changes, the following problems still exist: limited ability to soothe wound inflammation, insufficient sustained delivery of active ingredients in a moist wound environment, and difficulty in stably dispersing simple oily repair components in a hydrocolloid system. Guaifenesin, also known as guaiac oil, has anti-inflammatory, soothing, and repairing effects, but its poor water solubility easily leads to uneven dispersion, precipitation, discoloration, and decreased activity when directly added to hydrocolloid or aqueous systems. Therefore, there is a need for a composite hydrocolloid material that can combine the functions of wetting and liquid absorption, anti-adhesion and pain reduction, oil phase lubrication, and stable sustained release of guaiac. Summary of the Invention

[0003] The purpose of this invention is to provide a hydrocolloid material containing guaiac, its preparation method and application, and to solve the problems of poor dispersion stability, easy degradation of active ingredients, insufficient soothing and repair capabilities of ordinary hydrocolloid dressings, and insufficient stability of traditional oily wound materials combined with hydrocolloid materials when guaiac is directly added to hydrocolloid materials.

[0004] The objective of this invention can be achieved through the following technical solutions: A hydrocolloid material containing guaiac includes a backing layer and a hydrocolloid functional layer disposed on one side of the backing layer. The hydrocolloid functional layer comprises a hydrophobic elastomer matrix, pre-wetted hydrophilic absorbent powder, a composite plant repair oil, and guaiac nanoliposome lyophilized powder. The hydrophobic elastomer matrix comprises polyisobutylene, styrene-isoprene-styrene block copolymer, tackifying resin, and liquid paraffin, and optionally contains caprylic / capric triglycerides. The pre-wetted hydrophilic... The liquid-absorbing powder includes sodium carboxymethyl cellulose, pectin, gelatin, calcium alginate, sodium alginate, and caprylic / capric triglycerides; the compound plant repair oil includes Phellodendron amurense lipid dispersion, Lithospermum erythrorhizon-Angelica dahurica extract oil, Borage oil, Stellera chamaejasminoides seed oil, borneol, and DL-α-tocopherol; the guaiac nanoliposome freeze-dried powder is obtained by sequentially coating a guaiac nanoliposome aqueous dispersion with quaternized chitosan and sodium hyaluronate, then adding a freeze-drying protectant and freeze-drying.

[0005] As a preferred embodiment of the present invention, the hydrocolloid functional layer comprises the following raw materials in parts by weight: 230-380 parts of polyisobutylene, 60-100 parts of styrene-isoprene-styrene block copolymer, 70-100 parts of tackifying resin, 40-70 parts of liquid paraffin, 0-12 parts of caprylic / capric triglyceride for the hydrophobic elastomer matrix, 180-220 parts of sodium carboxymethyl cellulose, 40-100 parts of pectin, 30-50 parts of gelatin, 30-40 parts of calcium alginate, 10 parts of sodium alginate, 8-30 parts of caprylic / capric triglyceride for pre-wetting the hydrophilic absorbent powder, 20-80 parts of compound plant repair oil, and 20-60 parts of guaiac nanoliposome lyophilized powder.

[0006] As a preferred technical solution of the present invention, the preparation method of the compound plant repair oil is as follows: Phellodendron bark is extracted by ethanol reflux, and the filtrate is collected and concentrated under reduced pressure to obtain a Phellodendron bark extract concentrate; the Phellodendron bark extract concentrate is mixed with soybean lecithin in anhydrous ethanol, and then distilled under reduced pressure to obtain a Phellodendron bark lipid dispersion; Lithospermum erythrorhizon and Angelica dahurica are added to an oil phase composed of sesame oil and caprylic / capric triglycerides, and extracted under nitrogen protection and light-protected conditions to obtain Lithospermum erythrorhizon-Angelica dahurica extract oil; after cooling the Lithospermum erythrorhizon-Angelica dahurica extract oil, the Phellodendron bark lipid dispersion, borage oil, sandalwood seed oil, borneol, and DL-α-tocopherol are added, stirred, and filtered to obtain the compound plant repair oil.

[0007] In a preferred embodiment of the present invention, during the preparation of the compound plant repair oil, the following components are used: 30-50 parts by weight of Phellodendron bark, 12-16 parts by weight of Phellodendron bark extract concentrate, 7-9 parts by weight of soybean lecithin; 70-90 parts by weight of Lithospermum erythrorhizon, 20-40 parts by weight of Angelica dahurica, 600-700 parts by weight of sesame oil, 300-350 parts by weight of caprylic / capric triglycerides; 880-920 parts by weight of Lithospermum erythrorhizon-Angelica dahurica extract oil, 18-24 parts by weight of Phellodendron bark lipid dispersion, 60-70 parts by weight of borage oil, 78-88 parts by weight of sandalwood seed oil, 6-8 parts by weight of borneol, and 2-3 parts by weight of DL-α-tocopherol.

[0008] As a preferred embodiment of the present invention, the preparation method of the guaiac nanoliposome aqueous dispersion is as follows: guaiac, hydrogenated phosphatidylcholine, soybean lecithin, cholesterol, dipalmitoylphosphatidylglycerol, distearate phosphatidylethanolamine-polyethylene glycol 2000, and DL-α-tocopherol are added to anhydrous ethanol and stirred under light-protected and nitrogen-protected conditions to obtain a guaiac lipid phase premix; trehalose, glycerol, and disodium ethylenediaminetetraacetate are added to a phosphate buffer solution with a pH of 6.6 and a concentration of 10 mmol / L, the phosphate buffer solution is added to make up the volume, and nitrogen is introduced for deoxygenation to obtain an aqueous phase protection solution; the guaiac lipid phase premix is ​​injected into the aqueous phase protection solution, stirred, and then subjected to high-pressure homogenization, followed by dialysis to remove ethanol, and the system mass is replenished to obtain the guaiac nanoliposome aqueous dispersion.

[0009] In a preferred embodiment of the present invention, during the preparation of the guaiac nanoliposome aqueous dispersion, the following components are used: guaiac (0.10-0.12 parts by weight), hydrogenated phosphatidylcholine (4-5 parts by weight), soybean lecithin (1.20-1.30 parts by weight), cholesterol (0.75-0.85 parts by weight), dipalmitoylphosphatidylglycerol (0.30-0.32 parts by weight), distearate phosphatidylethanolamine-polyethylene glycol 2000 (0.15-0.19 parts by weight), and DL-α-tocopherol (0.07-0.09 parts by weight). The aqueous protective solution contains 5.2-5.4 parts by weight of trehalose, 3.1-3.3 parts by weight of glycerol, and 0.02-0.03 parts by weight of disodium ethylenediaminetetraacetate. The high-pressure homogenization process is carried out at a pressure of 500-600 bar, 4-5 times, and at a temperature of 35-40°C. The dialysis is performed using a dialysis bag with a molecular weight cutoff of 8-14 kDa, with a phosphate buffer solution at pH 6.6 and a concentration of 10 mmol / L as the dialysis medium, at a temperature of 4-10°C, and for a duration of 6-10 hours.

[0010] As a preferred embodiment of the present invention, based on 100 parts by weight of guaiac nanoliposome aqueous dispersion, the quaternized chitosan solution is 0.4-0.6 parts by weight, the sodium hyaluronate solution is 0.2-0.4 parts by weight, the trehalose is 5-7 parts by weight, and the mannitol is 1.5-2.5 parts by weight.

[0011] Another object of the present invention is to provide a method for preparing a hydrocolloid material containing guaiac, comprising the following steps: S1. Preparation of compound plant repair oil; S2. Preparation of guaiac nanoliposome aqueous dispersion; S3. The aqueous dispersion of guaiac nanoliposomes was coated with a double layer using quaternized chitosan and sodium hyaluronate, and then trehalose and mannitol were added for freeze-drying to obtain freeze-dried guaiac nanoliposome powder. S4. Polyisobutylene, styrene-isoprene-styrene block copolymer, tackifying resin and liquid paraffin, optionally including octanoic acid / decanoic acid triglyceride, are added to a vacuum kneader and stirred and melted under vacuum to obtain a hydrophobic elastomer matrix. S5. After mixing sodium carboxymethyl cellulose, pectin, gelatin, calcium alginate and sodium alginate evenly, add caprylic / capric triglyceride and stir to obtain pre-wetted hydrophilic liquid-absorbing powder. S6. After cooling the hydrophobic elastomer matrix, add the pre-wetted hydrophilic absorbent powder, stir under vacuum, then add the composite plant repair oil and the guaiac nanoliposome freeze-dried powder in sequence, mix and coat it on the backing layer, composite release film, cool and cut and package to obtain the guaiac-containing hydrocolloid material.

[0012] As a preferred embodiment of the present invention, the vacuum stirring melting temperature is 115-120℃ and the time is 60-80 min; when adding pre-wetted hydrophilic absorbent powder, the temperature of the hydrophobic elastomer matrix is ​​75-80℃; when adding composite plant repair oil, the system temperature is 50-55℃; when adding guaiac nanoliposome freeze-dried powder, the system temperature is 40-43℃; the coating thickness is 0.5-1.2 mm; and the backing layer is a polyurethane film.

[0013] Another object of the present invention is to provide an application of a hydrocolloid material containing guaiac, wherein the application refers to using the hydrocolloid material containing guaiac in a wound care dressing.

[0014] The beneficial effects of this invention are: (1) The hydrocolloid material containing guaiac disclosed in this invention, its preparation method and application, adopts a hydrophobic elastomer matrix-composite plant repair oil-double-layer coated guaiac nanoliposome freeze-dried powder synergistic composite structure to form a multi-level structured delivery network in the hydrocolloid dressing system, thereby achieving stable encapsulation, sustained release and high uniform dispersion of guaiac.

[0015] (2) The hydrocolloid material containing guaiac disclosed in this invention, its preparation method, and its application involve preparing guaiac into nanoliposomes and sequentially coating them with quaternized chitosan and sodium hyaluronate in a double-layer interface. This creates a stable alternating structure of positive and negative charges on the surface of the liposomes, effectively inhibiting electrostatic neutralization aggregation and hydrophobic agglomeration between the liposomes. Simultaneously, the double-layer coating structure improves the interfacial compatibility between the liposomes and the hydrocolloid matrix, enabling them to be uniformly dispersed in the three-dimensional network formed by the hydrophobic elastomer matrix and the hydrophilic absorbent component.

[0016] (3) The hydrocolloid material containing guaiac disclosed in this invention, its preparation method, and its application effectively improve the density and anti-leakage ability of the liposome membrane structure by introducing aqueous protective components such as trehalose, glycerol, and disodium EDTA into the liposome system and combining high-pressure homogenization and dialysis processes. On this basis, the outer composite polysaccharide membrane structure formed by quaternized chitosan and sodium hyaluronate further enhances the interfacial stability of the liposomes. At the same time, during the freeze-drying process, trehalose and mannitol form a glassy protective structure, effectively preventing the liposomes from collapsing and fusing under the action of ice crystal formation and drying stress, thereby significantly reducing the increase in particle size and drug leakage after reconstitution.

[0017] (4) The hydrocolloid material containing guaiac disclosed in this invention, its preparation method and application, through the synergistic effect of the bilayer coated liposome structure and the hydrocolloid network, requires guaiac to undergo three processes in sequence during the release process: liposome membrane diffusion, bilayer polysaccharide interface desorption and hydrocolloid matrix diffusion, thereby significantly prolonging the diffusion path and reducing the initial release rate; at the same time, the oil phase microenvironment formed by the compound plant repair oil provides further physical barrier effect on the liposome, so that the active ingredients are continuously released.

[0018] (5) The hydrocolloid material containing guaiac disclosed in this invention, its preparation method and application, construct a composite plant repair oil system and form a multi-component synergistic oil phase structure, so that the oil phase forms a stable dispersion micro-region in the hydrocolloid matrix; through the synergistic effect of hydrophobic elastomer matrix and hydrophilic liquid-absorbing powder, a hydrophobic-hydrophilic bicontinuous phase structure is constructed, thereby reducing the risk of oil phase migration and exudation. Detailed Implementation

[0019] The claims of the present invention will be further described in detail below with reference to specific embodiments, but this does not constitute any limitation on the present invention. Any limited modifications made by any person within the scope of protection of the claims of the present invention are still within the scope of protection of the claims of the present invention.

[0020] The following is an explanation of some of the raw materials used in this invention: Borage oil, homemade or sourced from Jiangxi Xinsen Natural Plant Oil Co., Ltd.

[0021] The method of making it is as follows: Take mature borage seeds, wash them, dry them under hot air at 40℃ until the seed moisture content drops to 5%, crush and press them into embryos, put them into a screw oil press, cold press them at 40℃ to extract oil, filter them through a 200-mesh filter cloth, and then centrifuge them at 5000r / min for 30min to remove suspended impurities and obtain primary borage seed oil. The primary borage seed oil was added to an 8 wt% citric acid aqueous solution and stirred at 45°C for 40 min for acidification and degumming. The gum layer was then separated by centrifugation to obtain degummed borage seed oil. The mass ratio of the primary borage seed oil to the citric acid aqueous solution was 100:3. The degummed borage seed oil was treated with activated carbon adsorption at a temperature of 45°C for 40 minutes, filtered, and then vacuum-devoured at 55°C for 1 hour to obtain the final product.

[0022] Sea buckthorn seed oil, either homemade or sourced from Guangzhou Xinsimei Biotechnology Co., Ltd.

[0023] The preparation method is as follows: Take mature sandalwood fruit, remove the pericarp and pulp, separate the sandalwood seeds, wash and remove impurities, dry them under 40℃ hot air conditions until the moisture content drops to 5%, crush and press the embryo, put it into a screw oil press, and cold press it under 40℃ conditions to obtain sandalwood seed crude oil, let it stand for 24 hours, then filter it through a 200-mesh filter cloth, and centrifuge it at 5000r / min for 20 minutes to obtain primary sandalwood seed oil; The primary sea sandalwood seed oil was added to an 8 wt% citric acid aqueous solution and stirred at 45°C for 40 min for acidification and degumming treatment. The gum layer was then separated by centrifugation to obtain degummed sea sandalwood seed oil. The mass ratio of the primary sea sandalwood seed oil to the citric acid aqueous solution was 100:4. The degummed sandalwood seed oil was treated with activated carbon adsorption at a temperature of 45°C for 40 minutes, filtered, and then vacuum-devoured at 50°C for 1 hour to obtain the final product.

[0024] Guaifenesin, CAS: 489-84-9, Hubei Yanke Times Technology Co., Ltd.; Dipalmitoylphosphatidylglycerol, CAS: 67232-81-9, Shanghai Anyikang Biotechnology Co., Ltd.; Distearate phosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000), Shenzhen Zuoke Biotechnology Co., Ltd.; Quaternized chitosan, Guangdong Wengjiang Chemical Reagent Co., Ltd.; Polyisobutylene, food-grade polyisobutylene, CAS: 9003-27-4, Wuhan Xingzhongcheng Technology Co., Ltd.; Styrene-isoprene-styrene block copolymer, Shanxi Jinyang Pharmaceutical Excipients Co., Ltd.; Tackifying resin, hydrogenated resin H5-1001, CAS: 64742-16-1, Henghe Materials Technology Co., Ltd.; Liquid paraffin, Guangzhou Hewei Pharmaceutical Technology Co., Ltd.; Polyurethane membrane, Shanghai Guchen Biotechnology Co., Ltd.

[0025] Example 1

[0026] Take 30g of Phellodendron bark, pulverize it to 50 mesh, add 300mL of 70% ethanol aqueous solution, and extract by reflux at 55℃ for 1h, then filter. The residue is then extracted once more with 200mL of 70% ethanol aqueous solution. The filtrates are combined and the mixture is concentrated under reduced pressure at -0.08MPa, 50℃, and 30r / min to recover ethanol and further concentrate until a relative density of 1.25 is obtained, yielding a concentrated Phellodendron bark extract. Take 12g of the concentrated Phellodendron bark extract, add 7g of soybean lecithin and 70mL of anhydrous ethanol, stir at 45℃ for 30min, and then remove the ethanol under reduced pressure. A lipid dispersion of Phellodendron bark was obtained. 70g of Lithospermum erythrorhizon and 20g of Angelica dahurica were pulverized to 40 mesh and added to an oil phase composed of 600g of sesame oil and 300g of caprylic / capric triglycerides. Under nitrogen protection and light protection, the mixture was stirred and extracted at 95℃ for 1.5h. The residue was removed by filtration to obtain Lithospermum erythrorhizon-Angelica dahurica extract oil. 880g of the Lithospermum erythrorhizon-Angelica dahurica extract oil was cooled to 40℃ and 18g of the lipid dispersion of Phellodendron bark, 60g of borage oil, 78g of sandalwood seed oil, 6g of borneol, and 2g of DL-α-tocopherol were added. The mixture was stirred for 30min and filtered through a 150-mesh filter cloth to obtain a compound plant repair oil.

[0027] Under stirring, 0.10 g of guaiac, 4 g of hydrogenated phosphatidylcholine, 1.20 g of soybean lecithin, 0.75 g of cholesterol, 0.30 g of dipalmitoylphosphatidylglycerol, 0.15 g of distearate-phosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000), and 0.07 g of DL-α-tocopherol were added to 30 mL of anhydrous ethanol. The mixture was stirred at 45 °C for 30 min under nitrogen protection in the dark to obtain a guaiac lipid premix. 5.2 g of trehalose, 3.1 g of glycerol, and 0.02 g of disodium ethylenediaminetetraacetate were dissolved in 65 g of a 10 mmol / L phosphate buffer solution (pH 6.6). The solution was then added to maintain the desired consistency. The volume was increased to 100g; nitrogen gas was continuously purged for 10min to remove dissolved oxygen, yielding an aqueous protective solution; under light-protected conditions, the aqueous protective solution was heated to 40℃ and injected into the guaiac lipid premix at a flow rate of 1mL / min with stirring at 1000r / min. Stirring was continued for 20min, followed by high-pressure homogenization. The mixture was then placed in a dialysis bag with a molecular weight cutoff of 8kDa. A phosphate buffer solution with a pH of 6.6 and a concentration of 10mmol / L was used as the dialysis medium. Dialysis was performed at 4℃ under light-protected conditions for 6h, with the dialysis medium replaced every 2h to remove ethanol from the system. After dialysis, the phosphate buffer solution was used to replenish the system mass, yielding an aqueous dispersion of guaiac nanoliposomes. The high-pressure homogenization process was performed at a pressure of 500 bar, with four homogenization cycles and a temperature of 35°C. 0.05 g of quaternized chitosan was added to 9.95 g of a 10 mmol / L phosphate buffer solution (pH 6.6), and stirred at 25°C for 30 min to obtain a 0.5 wt% quaternized chitosan solution. 0.03 g of sodium hyaluronate was added to 9.97 g of a 10 mmol / L phosphate buffer solution (pH 6.6), and stirred at 25°C for 1 h to allow for complete swelling and dissolution, yielding a 0.3 wt% sodium hyaluronate solution. Under stirring at 500 r / min, the quaternized chitosan solution was added dropwise to the guaiac nanoliposome aqueous dispersion. After the addition was completed, stirring was continued for 20 minutes, and then 0.3 wt% sodium hyaluronate solution was added dropwise, and stirring was continued for 20 minutes to obtain a double-layer coated guaiac nanoliposome dispersion. 100 g of the double-layer coated guaiac nanoliposome dispersion was taken, and 5 g of trehalose and 1.5 g of mannitol were added. After stirring evenly, the mixture was pre-frozen at -40°C for 6 hours to completely freeze the system. Subsequently, it was placed in a freeze dryer and vacuum freeze-dried for 12 hours under the conditions that the cold trap temperature was not higher than -50°C, the absolute pressure of the chamber was 10 Pa, and the shelf temperature was -20°C. Then, the shelf temperature was raised to 20°C, and a second vacuum drying was carried out for 4 hours under the conditions that the absolute pressure of the chamber was 5 Pa to obtain guaiac nanoliposome lyophilized powder.

[0028] Take 380g of polyisobutylene, 60g of styrene-isoprene-styrene block copolymer, 100g of tackifying resin, 70g of liquid paraffin, and 12g of caprylic / capric triglyceride and add them to a vacuum kneader. Stir and melt under vacuum at 115℃ for 60min to obtain a hydrophobic elastomer matrix. Take 220g of sodium carboxymethyl cellulose, 40g of pectin, 30g of gelatin, 30g of calcium alginate, and 10g of sodium alginate and mix them evenly. Add 8g of caprylic / capric triglyceride and stir for 10min to obtain a pre-wetting hydrophilic absorbent powder. The hydrophobic elastomer matrix was cooled to 75°C, and the pre-wetted hydrophilic absorbent powder was added. The mixture was stirred under vacuum for 30 minutes. The system temperature was then lowered to 50°C, and 20g of the composite plant repair oil was added and stirred for 15 minutes. The system temperature was further lowered to 40°C, and 20g of guaiac nanoliposome lyophilized powder was added. The mixture was stirred under vacuum for 8 minutes. The resulting mixture was coated onto a polyurethane film with a coating thickness of 0.5mm. A release film was then laminated, cooled, cut, and packaged to obtain a hydrocolloid material containing guaiac.

[0029] Example 2

[0030] Take 40g of Phellodendron bark, pulverize it to 60 mesh, add 400mL of 70% ethanol aqueous solution, and extract by reflux at 60℃ for 1.5h, then filter. The residue is then extracted twice more with 300mL of 70% ethanol aqueous solution. The filtrates are combined and the mixture is concentrated under reduced pressure at -0.085MPa, 55℃, and 45r / min to recover ethanol and further concentrate until a relative density of 1.30 is obtained, yielding a concentrated Phellodendron bark extract. Take 14g of the concentrated Phellodendron bark extract, add 8g of soybean lecithin and 80mL of anhydrous ethanol, stir at 50℃ for 35min, and then remove the ethanol under reduced pressure. A lipid dispersion of Phellodendron bark was obtained. 80g of Lithospermum erythrorhizon and 30g of Angelica dahurica were pulverized to 50 mesh and added to an oil phase composed of 650g of sesame oil and 325g of caprylic / capric triglycerides. The mixture was stirred and extracted at 95℃ for 2.0h under nitrogen protection and in the dark. The residue was removed by filtration to obtain Lithospermum erythrorhizon-Angelica dahurica extract oil. 900g of the Lithospermum erythrorhizon-Angelica dahurica extract oil was cooled to 45℃, and 21g of the lipid dispersion of Phellodendron bark, 65g of borage oil, 83g of sandalwood seed oil, 7g of borneol, and 2.5g of DL-α-tocopherol were added. The mixture was stirred for 35min and filtered through a 200-mesh filter cloth to obtain a compound plant repair oil.

[0031] Under stirring, 0.11 g of guaiac, 4.5 g of hydrogenated phosphatidylcholine, 1.25 g of soybean lecithin, 0.80 g of cholesterol, 0.31 g of dipalmitoylphosphatidylglycerol, 0.17 g of distearate-phosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000), and 0.08 g of DL-α-tocopherol were added to 40 mL of anhydrous ethanol. The mixture was stirred at 48 °C for 35 min under nitrogen protection in the dark to obtain a guaiac lipid premix. 5.3 g of trehalose, 3.2 g of glycerol, and 0.025 g of disodium ethylenediaminetetraacetate were dissolved in 70 g of a 10 mmol / L phosphate buffer solution (pH 6.6). The solution was then replenished to a final concentration. The volume was increased to 100g; nitrogen gas was continuously purged for 12min to remove dissolved oxygen, yielding an aqueous protective solution; under light-protected conditions, the aqueous protective solution was heated to 43℃ and injected into the guaiac lipid premix at a flow rate of 1.5mL / min with stirring at 1500r / min. Stirring was continued for 25min, followed by high-pressure homogenization. The mixture was then placed in a dialysis bag with a molecular weight cutoff of 11kDa. A phosphate buffer solution with a pH of 6.6 and a concentration of 10mmol / L was used as the dialysis medium. Dialysis was performed at 5℃ under light-protected conditions for 8h, with the dialysis medium replaced every 2h to remove ethanol from the system. After dialysis, the phosphate buffer solution was used to replenish the system mass, yielding an aqueous dispersion of guaiac nanoliposomes. The high-pressure homogenization process was performed at a pressure of 550 bar, with 5 homogenization cycles and a homogenization temperature of 38°C. 0.05 g of quaternized chitosan was added to 9.95 g of a 10 mmol / L phosphate buffer solution (pH 6.6), and stirred at 30°C for 45 min to obtain a 0.5 wt% quaternized chitosan solution. 0.03 g of sodium hyaluronate was added to 9.97 g of a 10 mmol / L phosphate buffer solution (pH 6.6), and stirred at 30°C for 1.5 h to allow for complete swelling and dissolution, resulting in a 0.3 wt% sodium hyaluronate solution. Under stirring at 650 r / min, the quaternized chitosan solution was added dropwise to the guaiac nanoliposome aqueous dispersion. After the addition was complete, stirring was continued for 25 minutes. Then, 0.3 wt% sodium hyaluronate solution was added dropwise, and stirring was continued for 30 minutes to obtain a double-layer coated guaiac nanoliposome dispersion. 100 g of the double-layer coated guaiac nanoliposome dispersion was taken, and 6 g of trehalose and 2.0 g of mannitol were added. After stirring evenly, the mixture was pre-frozen at -35°C for 7 hours to completely freeze the system. Subsequently, it was placed in a freeze dryer and vacuum freeze-dried for 15 hours under the conditions that the cold trap temperature was not higher than -50°C, the absolute pressure of the chamber was 30 Pa, and the shelf temperature was -20°C. Then, the shelf temperature was raised to 22°C, and a second vacuum drying was carried out for 6 hours under the conditions that the absolute pressure of the chamber was 15 Pa to obtain guaiac nanoliposome lyophilized powder.

[0032] Take 300g of polyisobutylene, 80g of styrene-isoprene-styrene block copolymer, 90g of tackifying resin, and 50g of liquid paraffin and add them to a vacuum kneader. Stir and melt under vacuum at 118℃ for 70min to obtain a hydrophobic elastomer matrix. Take 190g of sodium carboxymethyl cellulose, 70g of pectin, 40g of gelatin, 30g of calcium alginate, and 10g of sodium alginate and mix them evenly. Add 20g of caprylic / capric triglyceride and stir for 15min to obtain a pre-wetted hydrophilic liquid-absorbing powder. The hydrophobic... The temperature of the elastomer matrix was lowered to 78°C, and the pre-wetted hydrophilic absorbent powder was added. The mixture was stirred under vacuum for 35 minutes, and the temperature of the system was lowered to 52°C. 70g of the composite plant repair oil was added and stirred for 20 minutes. The temperature of the system was further lowered to 43°C, and 50g of guaiac nanoliposome lyophilized powder was added. The mixture was stirred under vacuum for 12 minutes, and the resulting mixture was coated onto a polyurethane film with a coating thickness of 0.9mm. A release film was then laminated, cooled, cut, and packaged to obtain a hydrocolloid material containing guaiac.

[0033] Example 3

[0034] Take 50g of Phellodendron bark, pulverize it to 70 mesh, add 500mL of 70% ethanol aqueous solution, and extract by reflux at 65℃ for 2h, then filter. Repeat the extraction three times with 400mL of 70% ethanol aqueous solution. Combine the filtrates and concentrate under reduced pressure at -0.09MPa, 60℃, and 60r / min to recover ethanol and further concentrate to a relative density of 1.35 to obtain a concentrated Phellodendron bark extract. Take 16g of the concentrated Phellodendron bark extract, add 9g of soybean lecithin and 90mL of anhydrous ethanol, stir at 55℃ for 40min, then remove the ethanol under reduced pressure. A lipid dispersion of Phellodendron bark was obtained. 90g of Lithospermum erythrorhizon and 40g of Angelica dahurica were pulverized to 60 mesh and added to an oil phase composed of 700g of sesame oil and 350g of caprylic / capric triglycerides. The mixture was stirred and extracted at 95℃ for 2.5h under nitrogen protection and in the dark. The residue was removed by filtration to obtain Lithospermum erythrorhizon-Angelica dahurica extract oil. 920g of the Lithospermum erythrorhizon-Angelica dahurica extract oil was cooled to 50℃, and 24g of the lipid dispersion of Phellodendron bark, 70g of borage oil, 88g of sandalwood seed oil, 8g of borneol, and 3g of DL-α-tocopherol were added. The mixture was stirred for 40min and filtered through a 250-mesh filter cloth to obtain a compound plant repair oil.

[0035] Under stirring, 0.12 g of guaiazoline, 5 g of hydrogenated phosphatidylcholine, 1.30 g of soybean lecithin, 0.85 g of cholesterol, 0.32 g of dipalmitoylphosphatidylglycerol, 0.19 g of distearate-phosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000), and 0.09 g of DL-α-tocopherol were added to 50 mL of anhydrous ethanol. The mixture was stirred at 50 °C for 40 min under nitrogen protection in the dark to obtain a guaiazoline lipid premix. 5.4 g of trehalose, 3.3 g of glycerol, and 0.03 g of disodium EDTA were dissolved in 75 g of a 10 mmol / L phosphate buffer solution (pH 6.6). The solution was then added to bring the volume to a final level. The total mass was increased to 100g; nitrogen gas was continuously purged for 15min to remove dissolved oxygen from the system, yielding an aqueous protective solution; under light-protected conditions, the aqueous protective solution was heated to 45℃ and injected into the guaiac lipid premix at a flow rate of 2mL / min with stirring at 2000r / min. Stirring was continued for 30min, followed by high-pressure homogenization. The mixture was then placed in a dialysis bag with a molecular weight cutoff of 14kDa. A phosphate buffer solution with a pH of 6.6 and a concentration of 10mmol / L was used as the dialysis medium. Dialysis was performed at 10℃ under light-protected conditions for 10h, with the dialysis medium replaced every 2h to remove ethanol from the system. After dialysis, the system mass was replenished with the phosphate buffer solution to obtain an aqueous dispersion of guaiac nanoliposomes. The high-pressure homogenization process was performed at a pressure of 600 bar, with 5 homogenization cycles and a temperature of 40°C. 0.05 g of quaternized chitosan was added to 9.95 g of a 10 mmol / L phosphate buffer solution (pH 6.6), and stirred at 35°C for 60 min to obtain a 0.5 wt% quaternized chitosan solution. 0.03 g of sodium hyaluronate was added to 9.97 g of a 10 mmol / L phosphate buffer solution (pH 6.6), and stirred at 35°C for 2 h to allow for complete swelling and dissolution, resulting in a 0.3 wt% sodium hyaluronate solution. Under stirring at 800 r / min, the quaternized chitosan solution was added dropwise to the guaiac nanoliposome aqueous dispersion. After the addition was completed, stirring was continued for 30 minutes, and then 0.3 wt% sodium hyaluronate solution was added dropwise. Stirring was continued for 40 minutes to obtain a double-layer coated guaiac nanoliposome dispersion. 100 g of the double-layer coated guaiac nanoliposome dispersion was taken, and 7 g of trehalose and 2.5 g of mannitol were added. After stirring evenly, the mixture was pre-frozen at -30°C for 8 hours to completely freeze the system. Subsequently, it was placed in a freeze dryer and vacuum freeze-dried for 18 hours under the conditions of cold trap temperature not exceeding -50°C, chamber absolute pressure of 50 Pa, and shelf temperature of -20°C. Then, the shelf temperature was raised to 25°C, and a second vacuum drying was carried out for 8 hours under the condition of chamber absolute pressure of 30 Pa to obtain guaiac nanoliposome lyophilized powder.

[0036] Take 230g of polyisobutylene, 100g of styrene-isoprene-styrene block copolymer, 70g of tackifying resin, 40g of liquid paraffin, and 10g of caprylic / capric triglyceride and add them to a vacuum kneader. Stir and melt under vacuum at 120℃ for 80min to obtain a hydrophobic elastomer matrix. Take 180g of sodium carboxymethyl cellulose, 100g of pectin, 50g of gelatin, 40g of calcium alginate, and 10g of sodium alginate and mix them evenly. Add 30g of caprylic / capric triglyceride and stir for 20min to obtain a pre-wetting hydrophilic absorbent powder. The hydrophobic elastomer matrix was cooled to 80°C, and the pre-wetted hydrophilic absorbent powder was added. The mixture was stirred under vacuum for 40 minutes. The system temperature was then lowered to 55°C, and 80g of composite plant repair oil was added and stirred for 25 minutes. The system temperature was further lowered to 42°C, and 60g of guaiac nanoliposome lyophilized powder was added. The mixture was stirred under vacuum for 15 minutes. The resulting mixture was coated onto a polyurethane film with a coating thickness of 1.2mm. A release film was then laminated, cooled, cut, and packaged to obtain a hydrocolloid material containing guaiac.

[0037] Comparative Example 1 The difference from Example 2 is that 40g of Phellodendron bark was pulverized to 60 mesh, and 400mL of 70% ethanol aqueous solution was added. The mixture was refluxed at 60℃ for 1.5h and filtered. The residue was then extracted twice more with 300mL of 70% ethanol aqueous solution. The filtrates were combined and concentrated under reduced pressure at -0.085MPa, 55℃, and 45r / min to a relative density of 1.30 to obtain a concentrated Phellodendron bark extract. 14g of the concentrated Phellodendron bark extract was added to 8g of soybean lecithin and 80mL of anhydrous ethanol. The mixture was stirred at 50℃ for 35min and the ethanol was removed under reduced pressure to obtain a Phellodendron bark lipid dispersion. 80g of Lithospermum erythrorhizon and 30g of Angelica dahurica were added to an oil phase composed of 650g of sesame oil and 325g of caprylic / capric triglycerides. The mixture was stirred and extracted at 95℃ under nitrogen protection for 2h. The mixture was filtered to remove residue, yielding an extract of Lithospermum erythrorhizon and Angelica dahurica. 900g of this extract was cooled to 45°C, and 21g of Phellodendron amurense lipid dispersion, 65g of Borage oil, 83g of Stellera chamaejasminoides seed oil, 7g of borneol, and 2.5g of DL-α-tocopherol were added. The mixture was stirred for 35 minutes and then filtered through a 200-mesh filter cloth to obtain a composite plant repair oil. At 45°C, 0.11g of Guaifenesin was directly added to the composite plant repair oil, and the mixture was stirred for 30 minutes to ensure uniform dispersion, resulting in an oil phase system containing Guaifenesin. Simultaneously, blank liposome lyophilized powder was prepared using the same method as in Example 2, but without the addition of Guaifenesin. In the preparation of the hydrocolloid material, 50g of the blank liposome lyophilized powder was used to replace 50g of the Guaifenesin nanoliposome lyophilized powder in Example 2, with the remaining components and process conditions remaining the same as in Example 2.

[0038] Comparative Example 2 The difference from Example 2 is that the quaternized chitosan and sodium hyaluronate coating treatment is not performed: 100g of the obtained guaiac nanoliposome aqueous dispersion is taken, 6g of trehalose and 2.0g of mannitol are added, and after stirring evenly, it is pre-frozen at -35℃ for 7h to make the system completely frozen; then it is placed in a freeze dryer and vacuum freeze-dried for 15h under the conditions that the cold trap temperature is not higher than -50℃, the absolute pressure of the cavity is 30Pa, and the shelf temperature is -20℃; then the shelf temperature is raised to 22℃ and vacuum dried for 6h under the conditions that the absolute pressure of the cavity is 15Pa to obtain guaiac nanoliposome freeze-dried powder.

[0039] Comparative Example 3 The difference from Example 2 is that 921g of the purple gromwell-angelica extract oil was cooled to 45°C, and 65g of borage oil, 83g of sandalwood seed oil, 7g of borneol and 2.5g of DL-α-tocopherol were added. The mixture was stirred for 35 minutes and filtered through a 200-mesh filter cloth to obtain a compound plant repair oil.

[0040] Comparative Example 4 The difference from Example 2 is that 110g of Lithospermum erythrorhizon was crushed to 50 mesh and added to an oil phase consisting of 650g of sesame oil and 325g of caprylic / capric triglycerides. Under nitrogen protection and light-proof conditions, the mixture was stirred and extracted at 95°C for 2.0h. After filtration to remove residue, Lithospermum erythrorhizon extract oil was obtained. 900g of the Lithospermum erythrorhizon extract oil was cooled to 45°C and 21g of the Phellodendron amurense lipid dispersion, 65g of borage oil, 83g of sandalwood seed oil, 7g of borneol, and 2.5g of DL-α-tocopherol were added. The mixture was stirred for 35min and filtered through a 200-mesh filter cloth to obtain a compound plant repair oil.

[0041] Comparative Example 5 The difference from Example 2 is that 110g of Angelica dahurica was pulverized to 50 mesh and added to an oil phase consisting of 650g of sesame oil and 325g of caprylic / capric triglycerides. Under nitrogen protection and light-proof conditions, the mixture was stirred and extracted at 95°C for 2.0h. After filtration to remove residue, Angelica dahurica extract oil was obtained. 900g of the Angelica dahurica extract oil was cooled to 45°C and 21g of Phellodendron amurense lipid dispersion, 65g of borage oil, 83g of sandalwood seed oil, 7g of borneol, and 2.5g of DL-α-tocopherol were added. The mixture was stirred for 35min and filtered through a 200-mesh filter cloth to obtain a compound plant repair oil.

[0042] Comparative Example 6 The difference from Example 2 is that 965g of the purple gromwell-angelica extract oil was cooled to 45°C, and 21g of the phellodendron lipid dispersion, 83g of sandalwood seed oil, 7g of borneol and 2.5g of DL-α-tocopherol were added. The mixture was stirred for 35 minutes and filtered through a 200-mesh filter cloth to obtain the compound plant repair oil.

[0043] Comparative Example 7 The difference from Example 2 is that 983g of the purple gromwell-angelica extract oil was cooled to 45°C, and 21g of the phellodendron lipid dispersion, 65g of borage oil, 7g of borneol and 2.5g of DL-α-tocopherol were added. The mixture was stirred for 35 minutes and filtered through a 200-mesh filter cloth to obtain the compound plant repair oil.

[0044] Comparative Example 8 The difference from Example 2 is that 650g of sesame oil and 325g of caprylic / capric triglycerides were stirred at 95°C under nitrogen protection for 2 hours without adding any Chinese medicinal materials, and the mixture was filtered to obtain the base oil. 921g of the base oil was cooled to 45°C, and 65g of borage oil, 83g of sandalwood seed oil, 7g of borneol and 2.5g of DL-α-tocopherol were added. The mixture was stirred for 35 minutes and filtered through a 200-mesh filter cloth to obtain a simplified compound oil. The remaining operations and steps remained unchanged.

[0045] Comparative Example 9 The difference from Example 2 is that borage oil and sandalwood seed oil are not added; 900g of the purple gromwell-angelica extract oil is cooled to 45°C, and 21g of the phellodendron chinense lipid dispersion, 148g of base oil composed of sesame oil and caprylic / capric triglycerides in a 2:1 mass ratio, 7g of borneol and 2.5g of DL-α-tocopherol are added. The mixture is stirred for 35 minutes and filtered through a 200-mesh filter cloth to obtain a compound plant repair oil. The remaining operations and steps remain unchanged.

[0046] Comparative Example 10 The difference from Example 2 is that, under stirring at 650 r / min, the quaternized chitosan solution was added dropwise to the guaiac nanoliposome aqueous dispersion. After the addition was completed, stirring was continued for 25 min to obtain a monolayer-treated guaiac nanoliposome dispersion. 100 g of the monolayer-treated guaiac nanoliposome dispersion was taken, and 6 g of trehalose and 2.0 g of mannitol were added. After stirring evenly, the mixture was pre-frozen at -35°C for 7 h to completely freeze the system. Subsequently, it was placed in a freeze dryer and vacuum freeze-dried for 15 h under the conditions of cold trap temperature not exceeding -50°C, chamber absolute pressure of 30 Pa, and shelf temperature of -20°C. Then, the shelf temperature was raised to 22°C, and a second vacuum drying was performed for 6 h under the condition of chamber absolute pressure of 15 Pa to obtain guaiac nanoliposome lyophilized powder. The remaining operations and steps remained unchanged.

[0047] Comparative Example 11 The difference from Example 2 is that, instead of adding quaternized chitosan solution, 0.3 wt% sodium hyaluronate solution was directly added dropwise to the guaiac nanoliposome aqueous dispersion under stirring at 650 r / min. After the addition was completed, stirring was continued for 30 min to obtain a monolayer-treated guaiac nanoliposome dispersion. Subsequently, lyophilized powder was prepared under the same lyophilization conditions as in Example 2, and hydrocolloid materials were prepared using the same process as in Example 2.

[0048] Performance testing The following performance tests were performed on the samples obtained from Examples 1-3 and Comparative Examples 1-11: 1) Test on the dispersion uniformity of guaiac in hydrocolloid materials.

[0049] Each group of hydrocolloid materials was cut into 10cm × 10cm samples. Samples were taken from nine locations (top left, top center, top right, left center, center, right center, bottom left, bottom center, and bottom right) using a 3x3 grid. The mass of each sample was 0.10g. After cutting the samples into smaller pieces, 10mL of methanol was added, and the samples were extracted by sonication for 30min. After centrifugation, the supernatant was collected, and the guaiac content at each sampling point was determined using high-performance liquid chromatography (HPLC). The relative standard deviation (RSD) of the guaiac content at the nine sampling points was calculated. The RSD of the guaiac content was calculated using the following formula: RSD = RSD of guaiac content at each sampling point / Average guaiac content at each sampling point × 100%.

[0050] Meanwhile, the sample was placed against a white background to observe the uniformity of surface color, and the surface and cross-section of the hydrocolloid layer were observed using a stereomicroscope. The number of blue agglomerates, spots, or local precipitation points was recorded and expressed as the number of visible agglomerates per unit area.

[0051] 2) Stability test of lyophilized and reconstituted guaiac nanoliposomes.

[0052] Take guaiac nanoliposome lyophilized powder and add 10 mmol / L phosphate buffer solution (pH 6.6) to the original volume before lyophilization. Gently shake for 5 min to reconstitute the solution. Dilute the reconstituted solution to a suitable concentration with the same phosphate buffer solution. Use a dynamic light scattering particle size analyzer at 25℃ to determine the average particle size, polydispersity index, and surface potential after reconstitution. Take another 1 mL of the reconstituted solution and place it in an ultrafiltration centrifuge tube. Centrifuge at 8000 r / min for 20 min, collect the filtrate, and determine the free guaiac content. Take another equal volume of the reconstituted solution, add methanol to demulsify, and make up to volume to determine the total guaiac content. The content of guaiac was determined by high performance liquid chromatography (HPLC). The HPLC conditions were as follows: C18 column, 250 mm × 4.6 mm, 5 μm; mobile phase: methanol-water, v / v 85:15; flow rate: 1.0 mL / min; column temperature: 30 °C; detection wavelength: 285 nm, or the maximum absorption wavelength determined by full-wavelength scanning of guaiac standard; injection volume: 10 μL. An external standard curve was established using guaiac standard. The linear range was 0.5–100 μg / mL, and the correlation coefficient R0 was [not specified]. 2 Not less than 0.999. The guaiacol encapsulation efficiency is calculated using the following formula: Guaifenesin encapsulation efficiency = (total guaiacol content - free guaiacol content) / total guaiacol content × 100%; the guaiacol leakage rate after reconstitution is calculated using the following formula: Guaifenesin leakage rate after reconstitution = free guaiacol content after reconstitution / total guaiacol content after reconstitution × 100%.

[0053] 3) Guaiacone release performance test.

[0054] The Franz diffusion cell method was used. Hydrocolloid material was cut into circular pieces with the same effective diffusion area as the diffusion cell, with the backing layer facing outwards and the hydrocolloid layer facing the receiving liquid. The receiving liquid was a simulated wound solution containing 0.5 wt% polysorbate 80, maintained at 32°C, and stirred at 300 r / min. Samples were taken at 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h, with an equal volume of fresh receiving liquid added after each sampling. The guaiac content in the receiving liquid was determined by high-performance liquid chromatography (HPLC), and the cumulative release rate at each time point was calculated. The cumulative release rate at the nth time point was calculated using the following formula: Cumulative release rate (%) = [C n ×V0+V s ×ΣC i ] / M0×100%. Where, C n Vn represents the concentration of guaiazoline in the receiving solution at the nth time point, and V0 represents the total volume of the receiving cell. s ΣC represents the volume of each sample taken. i M0 represents the sum of guaiac concentrations in the sample solution from the 1st to the (n-1th)th sampling, and M0 represents the initial mass of guaiac in the sample.

[0055] 4) Accelerated stability and retention rate test of guaiac after simulated rinsing.

[0056] After sealing and packaging, each group of samples was placed in a constant temperature and humidity chamber at 40℃ and 75% relative humidity for 30 days. After sampling, the color, odor, surface spots, and oil phase precipitation of the samples were observed, and the remaining guaiacol content in the samples was determined using high performance liquid chromatography (HPLC). The guaiacol retention rate was calculated using the following formula: Guaiacol retention rate = Guaiacol content in the sample after 30 days of acceleration / Guaiacol content in the sample before acceleration × 100%.

[0057] Simultaneously, the sample was cut into 2cm × 2cm pieces and attached to the surface of a collagen membrane. Simulated wound fluid was added to the sample surface at a flow rate of 1mL / min for 10min. The sample was then removed, and guaiac was extracted using methanol via ultrasonication. The remaining amount of guaiac was determined using high-performance liquid chromatography (HPLC). The guaiac retention rate after simulated rinsing was calculated using the following formula: Guaiac retention rate after simulated rinsing = Guaiac content in the sample after rinsing / Guaiac content in the sample before rinsing × 100%.

[0058] 5) Stability test of compound plant repair oil and hydrocolloid material.

[0059] Each group of hydrocolloid materials was cut into 5cm × 5cm samples. After weighing the initial mass, the hydrocolloid layer was placed face down on pre-weighed filter paper and placed at 37℃ for 24 hours. After the test, the samples were removed, the change in filter paper mass was weighed, and whether oil spots appeared on the filter paper was observed. The oil phase precipitation rate was calculated using the following formula: Oil phase precipitation rate = Filter paper weight gain / Initial sample mass × 100%.

[0060] The samples were placed vertically in a 40℃ constant temperature chamber for 7 days. After the test, samples were taken from the upper, middle and lower parts of the samples, and methanol was used for ultrasonic extraction and the content of guaiac was determined. The relative standard deviation of the guaiac content in different parts was calculated.

[0061] 6) Basic performance testing of hydrocolloid dressings.

[0062] Liquid absorption test: Cut the sample into 5cm × 5cm pieces, weigh the initial mass, place them in simulated wound fluid with pH 7.2-7.4, and incubate at 37℃ for 24 hours. Remove the samples, hang them for 30 seconds to remove surface free liquid, and weigh the mass after absorption. The absorption volume is calculated using the following formula: Absorption volume = (Mass of sample after absorption - Initial sample mass) / Sample area × 100cm² 2 .

[0063] Liquid retention rate test: After completing the liquid absorption test, place the sample between two layers of filter paper and press it under 2 kPa pressure for 1 min. Weigh the sample after pressurization. The liquid retention rate is calculated using the following formula: Liquid retention rate = Mass of liquid retained by the sample after pressurization / Mass of liquid absorbed by the sample after absorption × 100%.

[0064] 180-degree peel strength test: Cut the sample into 25mm wide strips, attach them to the surface of a stainless steel plate or simulated skin substrate, roll them back and forth twice with a 2kg roller, let them stand for 20 minutes, and then perform a 180-degree peel test on a universal testing machine at a speed of 300mm / min. Record the average peel force during the stable peel stage, in N / 25mm.

[0065] 7) In vitro soothing and repair performance and cell compatibility test.

[0066] Nitric oxide release inhibition rate assay: A lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammation model was used. RAW264.7 cells were seeded in 96-well plates. After adhesion, they were pretreated with culture medium containing sample extract for 2 h, followed by the addition of LPS to a final concentration of 1 μg / mL, and cultured for another 24 h. Cell supernatant was collected, and nitrite content was measured using Griess reagent. The LPS model group was used as a control, and the nitric oxide release inhibition rate was calculated. The nitric oxide release inhibition rate was calculated using the following formula: Nitric oxide release inhibition rate = (Nitrite content in the model group - Nitrite content in the sample group) / Nitrite content in the model group × 100%.

[0067] Human keratinocyte scratch closure rate test: HaCaT human keratinocytes were seeded in 6-well plates and cultured until the cell confluence was approximately 90%. Linear scratches were made using a sterile pipette tip, and after washing with PBS, low-serum culture medium containing sample extract was added. The scratch area was photographed and recorded at 0h and 24h, and the scratch closure rate was calculated using image analysis software. The scratch closure rate was calculated using the following formula: Scratch closure rate = (0h scratch area - 24h scratch area) / 0h scratch area × 100%.

[0068] In vitro cytotoxicity test: Press the sample 3cm apart 2 The extract was added to serum-containing cell culture medium at a ratio of / mL and extracted at 37℃ for 24h. The extract was then co-cultured with L929 mouse fibroblasts for 24h, and the relative cell viability was detected using the CCK-8 assay. The relative cell viability was calculated using the following formula: Relative cell viability = Absorbance of sample group / Absorbance of blank control group × 100%.

[0069] The test results are shown in Tables 1-7 below: Table 1

[0070] Table 2

[0071] Table 3

[0072] Table 4

[0073] Table 5

[0074] Table 6

[0075] Table 7

[0076] As shown in Table 1, the guaiac content in the hydrocolloid materials obtained in Examples 1-3 is relatively uniform, indicating that the hydrocolloid materials obtained in this invention have good initial dispersion uniformity and short-term thermal stability. In Comparative Example 1, guaiac was directly added to the oil phase system, and the free guaiac easily underwent local enrichment, discoloration, and precipitation in the hydrocolloid material. Comparative Examples 2, 10, and 11, which respectively eliminated the double-layer coating or used only a single-layer treatment, showed that their dispersion uniformity and distribution stability after placement were inferior to those of Example 2.

[0077] Table 2 shows that the guaiac nanoliposome lyophilized powders obtained in Examples 1-3 maintained good particle size distribution and drug loading stability after reconstitution. Comparative Example 2, without quaternized chitosan and sodium hyaluronate coating, showed increased average particle size, polydispersity index, and leakage rate after reconstitution. Comparative Example 10 and Comparative Example 11, with only quaternized chitosan monolayer treatment and only sodium hyaluronate monolayer treatment, showed increased leakage rates after reconstitution.

[0078] As shown in Table 3, Examples 1-3 all exhibited relatively stable continuous release behavior of guaiac. Comparative Examples 2, 10, and 11 lacked double-layer coating or only used single-layer coating, respectively. Their 24-hour cumulative release rate was significantly higher than that of Example 2, indicating that when the coating structure is incomplete, guaiac is more likely to migrate rapidly from the liposome and hydrocolloid matrix to the receiving fluid.

[0079] Table 4 shows that the hydrocolloid materials obtained in Examples 1-3 have good stabilizing and protective effects against rinsing loss of guaiac. In Comparative Example 1, the guaiac retention rate decreased after 30 days of accelerated rinsing, the appearance color difference value increased, and the guaiac retention rate decreased after simulated rinsing. The accelerated stability and rinsing retention rate of Comparative Examples 2 and 11 also decreased significantly.

[0080] Table 5 shows that the compound plant repair oils of Examples 1-3 exhibit good compatibility stability with the hydrocolloid matrix. In Comparative Example 9, without the addition of borage oil and sandalwood seed oil, the oil phase precipitation rate increased after 24 hours, and the relative standard deviation of guaiac content distribution increased after 7 days of vertical storage at 40℃, along with the increased proportion of oil stains on the filter paper. In Comparative Example 7, after removing sandalwood seed oil, the oil phase precipitation rate and guaiac migration degree also significantly increased. In Comparative Example 8, without the addition of medicinal herb extracts, the oil phase precipitation rate and the relative standard deviation of guaiac content distribution were also higher than in Example 2.

[0081] As shown in Table 6, Examples 1-3 all maintained the basic liquid absorption, liquid retention, and peeling properties required for hydrocolloid dressings. The basic hydrocolloid properties of each comparative example were generally similar to those of Example 2, indicating that the introduction of guaiac nanoliposomes and the composite plant repair oil system did not significantly impair the basic performance of the hydrocolloid materials.

[0082] As shown in Table 7, Examples 1-3 all exhibited good in vitro soothing and repair properties and cell compatibility. In Comparative Example 3, after removing the Phellodendron amurense lipid dispersion, the nitric oxide release inhibition rate and scratch closure rate were both lower than in Example 2. Comparative Example 4 used only Lithospermum erythrorhizon extract oil, and Comparative Example 5 used only Angelica dahurica extract oil; both showed lower scratch closure rates and nitric oxide release inhibition rates than in Example 2. Comparative Example 8 did not include any herbal extracts; its nitric oxide release inhibition rate and HaCaT cell scratch closure rate after 24 hours were significantly lower than in Example 2. Although Comparative Examples 10 and 11 still contained Guaiacinthus and compound plant repair oil, their in vitro soothing and repair properties and stability were inferior to those of Example 2 due to incomplete liposome encapsulation structures.

[0083] In summary, at the level of inflammatory microenvironment regulation, the bilayer-encapsulated guaiac nanoliposomes, through their composite structure of a phospholipid bilayer core, a quaternized chitosan positively charged layer, and a sodium hyaluronate negatively charged layer, can form a stable interfacial delivery system upon contact with a moist wound environment.

[0084] At the lipid barrier repair level, the compound plant repair oil system consists of Phellodendron amurense lipid dispersion, Lithospermum erythrorhizon-Angelica dahurica extract oil, Borage oil, and Stellera chamaejasme seed oil. Through the synergistic effect of multiple components, it forms an oil-phase microstructure system with gradient polarity. Specifically, the phospholipids and polyphenols in the Phellodendron amurense lipid dispersion form a biomembrane-like structure at the oil-water interface, enhancing the interfacial anchoring ability of the oil phase in the hydrocolloid matrix. Lithospermum erythrorhizon-Angelica dahurica extract oil provides lipid-soluble active ingredients and participates in the local repair process. Borage oil regulates the lipid metabolism microenvironment through γ-linolenic acid, reducing the sensitivity to inflammation-related signals. Stellera chamaejasme seed oil enhances the compactness and anti-migration ability of the oil phase through its highly hydrophobic long-chain fatty acid structure, thus jointly achieving stable repair of the lipid barrier and sustained retention of active substances. Phospholipid molecules in the Phellodendron amurense lipid dispersion can self-assemble at the oil-water interface to form a biomembrane-like structure. Simultaneously, the polyphenols and flavonoids in the Phellodendron amurense extract can form weak interactions with carboxyl and hydroxyl groups in the hydrocolloid network through hydrogen bonding, thereby enhancing the interfacial binding ability between the oil and water phases. The extract oil of Lithospermum erythrorhizon and Angelica dahurica serves as the main active oil phase, rich in naphthoquinone structures from Lithospermum erythrorhizon and coumarin components from Angelica dahurica. These lipid-soluble active substances can form a continuous release source at the wound site. Lithospermum erythrorhizon components can participate in the regulation of the inflammatory microenvironment, reducing the level of local inflammatory mediators; Angelica dahurica components have certain penetration-promoting and microcirculation-regulating effects, improving the metabolic state of local tissues; the oil phase carriers, sesame oil and caprylic / capric triglycerides, provide suitable diffusion mediators, enabling the active ingredients to slowly migrate to the interface of action, thereby achieving continuous repair and regulation of the local inflammatory microenvironment. Borage oil, rich in γ-linolenic acid, can serve as a metabolic precursor for prostaglandins and inflammatory mediators, reducing the production of pro-inflammatory mediators in local lipid metabolism pathways; improving local lipid membrane fluidity, enhancing cell membrane stability; and reducing the sensitivity of inflammation-related signaling pathways. Sea buckthorn seed oil has a high proportion of long-chain fatty acid structure, which is highly hydrophobic and has high oxidative stability. In the oil phase system, it improves the overall hydrophobic compactness of the oil phase and reduces the oil droplet diffusion rate; it forms mixed oil phases with other vegetable oils, improving the viscoelasticity of the system; and it inhibits the migration and precipitation behavior of the oil phase in the hydrocolloid network, thereby enhancing the long-term stability and retention capacity of the entire composite oil phase system.

[0085] Guaiac nanoliposomes and Phellodendron amurense lipid dispersions jointly regulate the inflammatory microenvironment and reduce the release of inflammatory mediators; Lithospermum erythrorhizon-Angelica dahurica extract and Borage oil synergistically improve the local lipid metabolism environment and promote tissue repair; at the same time, Stellera chamaejasminoides seed oil enhances the stability of the oil phase structure and reduces the migration and degradation of active substances; in addition, the hydrocolloid network provides a continuous moist environment and physical barrier protection, thereby forming a synergistic enhancement effect in terms of structure delivery, lipid repair and anti-inflammatory regulation, achieving a significant improvement in soothing and repair effects and a prolonged duration of action.

Claims

1. A water gel material containing guaiazulene, comprising a backing layer and a water gel functional layer provided on one side of the backing layer, characterized in that, The hydrocolloid functional layer comprises a hydrophobic elastomer matrix, pre-wetted hydrophilic absorbent powder, a composite plant repair oil, and guaiac nanoliposome lyophilized powder. The hydrophobic elastomer matrix comprises polyisobutylene, styrene-isoprene-styrene block copolymer, tackifying resin, and liquid paraffin, and optionally contains caprylic / capric triglycerides. The pre-wetted hydrophilic absorbent powder comprises sodium carboxymethyl cellulose, pectin, gelatin, calcium alginate, sodium alginate, and caprylic / capric triglycerides. The composite plant repair oil comprises Phellodendron amurense lipid dispersion, Lithospermum erythrorhizon-Angelica dahurica extract oil, Borage oil, Stellera chamaejasminoides seed oil, borneol, and DL-α-tocopherol. The guaiac nanoliposome lyophilized powder is obtained by sequentially coating a guaiac nanoliposome aqueous dispersion with quaternized chitosan and sodium hyaluronate, then adding a lyophilization protectant and freeze-drying.

2. A water gel material containing guaiazulene according to claim 1, characterized by The hydrocolloid functional layer comprises the following raw materials in parts by weight: 230-380 parts of polyisobutylene, 60-100 parts of styrene-isoprene-styrene block copolymer, 70-100 parts of tackifying resin, 40-70 parts of liquid paraffin, 0-12 parts of caprylic / capric triglyceride for the hydrophobic elastomer matrix, 180-220 parts of sodium carboxymethyl cellulose, 40-100 parts of pectin, 30-50 parts of gelatin, 30-40 parts of calcium alginate, 10 parts of sodium alginate, 8-30 parts of caprylic / capric triglyceride for pre-wetting the hydrophilic absorbent powder, 20-80 parts of compound plant repair oil, and 20-60 parts of guaiac nanoliposome lyophilized powder.

3. The water gel material containing guaiazulene according to claim 1, characterized by, The preparation method of the compound plant repair oil is as follows: Phellodendron bark is extracted by ethanol reflux, and the filtrate is collected and concentrated under reduced pressure to obtain a concentrated extract; the concentrated extract is mixed with soybean lecithin in anhydrous ethanol, and then distilled under reduced pressure to obtain a lipid dispersion; Lithospermum erythrorhizon and Angelica dahurica are added to an oil phase composed of sesame oil and caprylic / capric triglycerides, and extracted under nitrogen protection and light-protected conditions to obtain Lithospermum erythrorhizon-Angelica dahurica extract oil; after cooling the Lithospermum erythrorhizon-Angelica dahurica extract oil, the lipid dispersion, borage oil, sea buckthorn seed oil, borneol, and DL-α-tocopherol are added, stirred, and filtered to obtain the compound plant repair oil.

4. A water gel material containing guaiazulene according to claim 3, characterized by In the preparation of the compound plant repair oil, the following components are used: 30-50 parts by weight of Phellodendron bark, 12-16 parts by weight of Phellodendron bark extract concentrate, 7-9 parts by weight of soybean lecithin; 70-90 parts by weight of Lithospermum erythrorhizon, 20-40 parts by weight of Angelica dahurica, 600-700 parts by weight of sesame oil, 300-350 parts by weight of caprylic / capric triglycerides; 880-920 parts by weight of Lithospermum erythrorhizon-Angelica dahurica extract oil, 18-24 parts by weight of Phellodendron bark lipid dispersion, 60-70 parts by weight of borage oil, 78-88 parts by weight of sandalwood seed oil, 6-8 parts by weight of borneol, and 2-3 parts by weight of DL-α-tocopherol.

5. A hydrocolloid material containing guaiac according to claim 1, characterized in that, The method for preparing the guaiac nanoliposome aqueous dispersion is as follows: guaiac, hydrogenated phosphatidylcholine, soybean lecithin, cholesterol, dipalmitoylphosphatidylglycerol, distearate phosphatidylethanolamine-polyethylene glycol 2000, and DL-α-tocopherol are added to anhydrous ethanol and stirred under light-protected and nitrogen-protected conditions to obtain a guaiac lipid phase premix; trehalose, glycerol, and disodium EDTA are added to a phosphate buffer solution with a pH of 6.6 and a concentration of 10 mmol / L, the phosphate buffer solution is added to make up the volume, and nitrogen is introduced for deoxygenation to obtain an aqueous phase protection solution; the guaiac lipid phase premix is ​​injected into the aqueous phase protection solution, stirred, and then subjected to high-pressure homogenization, followed by dialysis to remove ethanol, and the system mass is replenished to obtain the guaiac nanoliposome aqueous dispersion.

6. A water gel material containing guaiazulene according to claim 5, characterized by In the preparation of the guaiac nanoliposome aqueous dispersion, guaiac is 0.10-0.12 parts by weight, hydrogenated phosphatidylcholine is 4-5 parts by weight, soybean lecithin is 1.20-1.30 parts by weight, cholesterol is 0.75-0.85 parts by weight, dipalmitoylphosphatidylglycerol is 0.30-0.32 parts by weight, distearate phosphatidylethanolamine-polyethylene glycol 2000 is 0.15-0.19 parts by weight, and DL-α-tocopherol is 0.07-0.09 parts by weight; the aqueous phase protective solution contains... The composition of the trehalose is 5.2-5.4 parts by weight, the composition of the glycerol is 3.1-3.3 parts by weight, and the composition of the disodium ethylenediaminetetraacetate is 0.02-0.03 parts by weight. The high-pressure homogenization process is carried out at a pressure of 500-600 bar, with 4-5 homogenization cycles and a temperature of 35-40°C. The dialysis is performed using a dialysis bag with a molecular weight cutoff of 8-14 kDa, using a phosphate buffer solution with a pH of 6.6 and a concentration of 10 mmol / L as the dialysis medium, at a temperature of 4-10°C, for a duration of 6-10 hours.

7. The water gel material containing guaiazulene according to claim 1, characterized by Based on 100 parts by weight of guaiac nanoliposome aqueous dispersion, the quaternized chitosan solution is 0.4-0.6 parts by weight, the sodium hyaluronate solution is 0.2-0.4 parts by weight, the trehalose is 5-7 parts by weight, and the mannitol is 1.5-2.5 parts by weight.

8. A process for the preparation of a water-soluble guaiazulene-containing hydrogel material according to any one of claims 1 to 7, characterized in that, Includes the following steps: S1. Preparation of compound plant repair oil; S2. Preparation of guaiac nanoliposome aqueous dispersion; S3. The aqueous dispersion of guaiac nanoliposomes was coated with a double layer using quaternized chitosan and sodium hyaluronate, and then trehalose and mannitol were added for freeze-drying to obtain freeze-dried guaiac nanoliposome powder. S4. Polyisobutylene, styrene-isoprene-styrene block copolymer, tackifying resin and liquid paraffin, optionally including octanoic acid / decanoic acid triglyceride, are added to a vacuum kneader and stirred and melted under vacuum to obtain a hydrophobic elastomer matrix. S5. After mixing sodium carboxymethyl cellulose, pectin, gelatin, calcium alginate and sodium alginate evenly, add caprylic / capric triglyceride and stir to obtain pre-wetted hydrophilic liquid-absorbing powder. S6. After cooling the hydrophobic elastomer matrix, add the pre-wetted hydrophilic absorbent powder, stir under vacuum, then add the composite plant repair oil and the guaiac nanoliposome freeze-dried powder in sequence, mix and coat it on the backing layer, composite release film, cool and cut and package to obtain the guaiac-containing hydrocolloid material.

9. The method for preparing a hydrocolloid material containing guaiac according to claim 8, characterized in that, The vacuum stirring melting temperature is 115-120℃, and the time is 60-80 min; when adding pre-wetted hydrophilic absorbent powder, the temperature of the hydrophobic elastomer matrix is ​​75-80℃; when adding composite plant repair oil, the system temperature is 50-55℃; when adding guaiac nanoliposome freeze-dried powder, the system temperature is 40-43℃; the coating thickness is 0.5-1.2 mm; the backing layer is a polyurethane film.

10. Use of a watercolloid material containing guaiazulene according to any one of claims 1-7, characterized in that, The application refers to using the hydrocolloid material containing guaiac in wound care dressings.

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