A blumea balsam oil cream, a preparation method and application thereof

Abstract

This invention discloses an angelica oil ointment, its preparation method, and its application. The ointment uses angelica oil as the active ingredient and employs an O / W type ointment matrix. The optimal formulation and process were obtained through uniform design, response surface methodology, and orthogonal experiments. The ointment is composed of glyceryl monostearate, petrolatum, stearyl alcohol, liquid paraffin, Tween 80, sodium lauryl sulfate, glycerol, distilled water, and angelica oil, with an optimal drug loading of 10% (4.5 g / 45 g matrix). The preparation process uses an oil-water phase method, with an emulsification temperature of 80 ℃, an emulsification time of 15 min, and a stirring speed of 800 r / min. Pharmacological experiments confirmed that the ointment of this invention can significantly promote the healing of deep second-degree burns in rats, reduce the levels of inflammatory factors IL-1β, IL-6, and TNF-α, and does not cause skin dryness, desquamation, or cracking. It exhibits excellent stability and is suitable for clinical external use and industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to an angelica oil cream, its preparation method, and its application. Background Technology

[0002] Blumeabalsamifera oil (also known as Blumeabalsamifera volatile oil, BBoil) is derived from the fresh or dried aerial parts of Blumeabalsamifera (L.) DC., a plant belonging to the genus Blumeabals in the Asteraceae family. It possesses various medicinal properties, including analgesia, diaphoresis, dispelling wind and dampness, expectoration and cough relief, and promoting menstruation and hemostasis. It shows great potential for application in the treatment of burns and scalds. However, current techniques for applying Blumeabalsamifera oil primarily involve direct topical application of the oil, which has the following drawbacks: 1) It is highly irritating to the skin and can easily lead to dryness, peeling, and cracking around the wound; 2) Poor spreadability, making it difficult to apply evenly to the wound surface; 3) Poor stability; easily volatilized and lost. 4) The lack of standardized matrix formulations and preparation processes makes industrial production difficult.

[0003] Currently, there are no publicly available O / W type creams optimized for the properties of angelica oil, nor are their standardized preparation processes disclosed, which limits their clinical application. Summary of the Invention

[0004] The purpose of this invention is to provide an Amaranthus oil cream that can eliminate skin irritation such as dryness, peeling, and cracking caused by pure Amaranthus oil, while retaining and enhancing its burn healing effect and having good stability.

[0005] Another objective of this invention is to provide a method for preparing an anointing oil cream.

[0006] Another objective of this invention is to provide an application of anointing oil cream in the preparation of a medicine for treating deep second-degree burns.

[0007] To achieve the above objectives, the present invention provides the following technical solution: An angelica oil cream, by weight, comprises the following components: Active ingredient: 4.5 parts of Ebony oil; Oil phase components: 3-7 parts glyceryl monostearate, 3 parts petrolatum, 2 parts octadecanol, 3-7 parts liquid paraffin; Emulsifier: 2 parts Tween 80, 0.3-0.7 parts sodium dodecyl sulfate; Aqueous phase components: 6 parts glycerol, 17 parts distilled water; The cream is an O / W type with a drug loading of 10%.

[0008] Preferably, the present invention comprises 5-7 parts of glyceryl monostearate, 5-7 parts of liquid paraffin, and 0.5-0.7 parts of sodium dodecyl sulfate.

[0009] More preferably, the present invention comprises 5 parts of glyceryl monostearate, 5 parts of liquid paraffin, and 0.5 parts of sodium dodecyl sulfate.

[0010] A method for preparing an angelica oil cream includes the following steps: 1) Oil phase preparation: Glyceryl monostearate, petrolatum, octadecanol and liquid paraffin are mixed and heated to 75-80℃ until completely melted; 2) Aqueous phase preparation: Mix Tween 80, sodium dodecyl sulfate, glycerol, and distilled water, and heat to 75-80℃; 3) Emulsification: At 70-80℃ and a stirring speed of 800-1200r / min, slowly add the aqueous phase to the oil phase and keep it warm while stirring for 5-15min; 4) Adding medicine: Cool down to 40℃, add senna oil, stir well, and cool to room temperature.

[0011] The emulsification method of this invention is an oil-water phase method.

[0012] Preferably, the emulsification in step 3) of the present invention is as follows: at 75-80°C and a stirring speed of 800-1000 r / min, the aqueous phase is slowly added to the oil phase and stirred for 10-15 min while maintaining the temperature.

[0013] More preferably, the emulsification in step 3) of the present invention is as follows: at 80°C and a stirring speed of 800 r / min, the aqueous phase is slowly added to the oil phase and stirred for 15 min while maintaining the temperature.

[0014] The present invention relates to the application of the Aina sesame oil cream in the preparation of a medicine for treating deep second-degree burns.

[0015] Compared with the prior art, the present invention has the following beneficial effects: 1. Superior healing effect: The wound healing rate of the Aina sesame oil cream of this invention is significantly higher than that of the Aina sesame oil alone group, the model group, and the blank matrix group. The wound is basically healed by the 14th day. Histopathology shows that its skin tissue structure is closer to that of the normal control group. The healing effect is comparable to that of the positive drug group and some indicators are even better.

[0016] 2. Significantly improved drug safety: This invention completely solves the irritation problems such as dryness, peeling, and cracking of the skin around the wound caused by direct external application of pure Ayana balsam oil. Through the encapsulation, sustained release, and moisturizing effects of the cream, the safe delivery of the drug is achieved.

[0017] 3. Good formulation stability: The optimized cream of this invention showed no stratification, foaming, or clumping under conditions of -25℃ cold resistance, 60℃ heat resistance, and centrifugation at 7000r / min, meeting the quality standards for topical creams and solving the problems of easy loss, difficulty in application, and poor stability of Ayam oil.

[0018] 4. This invention is the first to determine the optimal drug loading and standardized preparation process, providing a repeatable technical solution for its industrial production and clinical application, and solving the problems of unclear dosage and lack of unified standard for preparation process of arugula oil. Attached Figure Description

[0019] Figure 1 A three-dimensional surface plot of the response surface of the interaction of various factors; Figure 2 The wound healing status of rats in each group at different time points; Figure 3 The wound healing trajectory of rats in each group at different time points; Figure 4 The wound healing rate of rats in each group at different time points; Figure 5 HE staining results of skin tissue samples taken from rats on days 7 and 14 of each group; Figure 6 The serum IL-1β levels of rats in each group on days 7 and 14; Figure 7 The serum IL-6 levels of rats in each group on days 7 and 14; Figure 8 The serum TNF-α levels of rats in each group on days 7 and 14 are shown. Detailed Implementation

[0020] The technical solution of the present invention will be further described in detail below through specific embodiments.

[0021] Example 1: Eau de Parfum Cream Formula: 4.5g of Eau de Parfum, 5g of Glyceryl Monostearate, 3g of Vaseline, 2g of Octadecyl Alcohol, 5g of Liquid Paraffin, 2g of Tween 80, 0.5g of Sodium Lauryl Sulfate, 6g of Glycerol, and 17g of Distilled Water.

[0022] The cream is an O / W type with a drug loading of 10%.

[0023] Example 2: Eau de Parfum Cream Formula: 4.5g of Eau de Parfum, 3g of Glyceryl Monostearate, 3g of Vaseline, 2g of Octadecyl Alcohol, 5g of Liquid Paraffin, 2g of Tween 80, 0.3g of Sodium Lauryl Sulfate, 6g of Glycerol, and 17g of Distilled Water.

[0024] Example 3: Eau de Parfum Cream Formula: 4.5g of Eau de Parfum, 7g of Glyceryl Monostearate, 3g of Vaseline, 2g of Octadecyl Alcohol, 3g of Liquid Paraffin, 2g of Tween 80, 0.5g of Sodium Lauryl Sulfate, 6g of Glycerol, and 17g of Distilled Water.

[0025] Example 4: Eau de Parfum Cream Formula: 4.5g of Eau de Parfum, 3g of Glyceryl Monostearate, 3g of Vaseline, 2g of Octadecyl Alcohol, 5g of Liquid Paraffin, 2g of Tween 80, 0.7g of Sodium Lauryl Sulfate, 6g of Glycerol, and 17g of Distilled Water.

[0026] Example 5: Eau de Parfum Cream Formula: 4.5g of Eau de Parfum, 3g of Glyceryl Monostearate, 3g of Vaseline, 2g of Octadecyl Alcohol, 3g of Liquid Paraffin, 2g of Tween 80, 0.5g of Sodium Lauryl Sulfate, 6g of Glycerol, and 17g of Distilled Water.

[0027] Example 6: Eau de Parfum Cream Formula: 4.5g of Eau de Parfum, 7g of Glyceryl Monostearate, 3g of Vaseline, 2g of Octadecyl Alcohol, 5g of Liquid Paraffin, 2g of Tween 80, 0.7g of Sodium Lauryl Sulfate, 6g of Glycerol, and 17g of Distilled Water.

[0028] Example 7: Eau de Parfum Cream Formula: 4.5g of Eau de Parfum, 5g of Glyceryl Monostearate, 3g of Vaseline, 2g of Octadecyl Alcohol, 3g of Liquid Paraffin, 2g of Tween 80, 0.7g of Sodium Lauryl Sulfate, 6g of Glycerol, and 17g of Distilled Water.

[0029] Example 8: Echeveria elegans oil cream Formula: 4.5g of Eau de Parfum, 5g of Glyceryl Monostearate, 3g of Vaseline, 2g of Octadecyl Alcohol, 7g of Liquid Paraffin, 2g of Tween 80, 0.7g of Sodium Lauryl Sulfate, 6g of Glycerol, and 17g of Distilled Water.

[0030] Example 9: Ebony Oil Cream Formula: 4.5g of Eau de Parfum, 3g of Glyceryl Monostearate, 3g of Vaseline, 2g of Octadecyl Alcohol, 7g of Liquid Paraffin, 2g of Tween 80, 0.5g of Sodium Lauryl Sulfate, 6g of Glycerol, and 17g of Distilled Water.

[0031] The formulations of the senna oil cream from Examples 1-9 above were used in the following preparation methods. Example 10: Preparation method of Echeveria elegans oil cream 1) Oil phase preparation: Glyceryl monostearate, petrolatum, octadecanol and liquid paraffin are mixed and heated to 75-80℃ until completely melted; 2) Aqueous phase preparation: Mix Tween 80, sodium dodecyl sulfate, glycerol, and distilled water, and heat to 75-80 °C; 3) Emulsification: At 80 ℃ and a stirring speed of 800 r / min, the aqueous phase is slowly added to the oil phase and stirred for 15 min while maintaining the temperature. 4) Adding medicine: Cool down to 40 ℃, add senna oil, stir well, and cool to room temperature.

[0032] The emulsification method is an oil-water phase method.

[0033] Example 11 Preparation method of Echeveria elegans oil cream 1) Oil phase preparation: Glyceryl monostearate, petrolatum, octadecanol and liquid paraffin are mixed and heated to 75-80℃ until completely melted; 2) Aqueous phase preparation: Mix Tween 80, sodium dodecyl sulfate, glycerol, and distilled water, and heat to 75-80 °C; 3) Emulsification: At 70 ℃ and a stirring speed of 1000 r / min, the aqueous phase is slowly added to the oil phase and stirred for 5 min while maintaining the temperature. 4) Adding medicine: Cool down to 40 ℃, add senna oil, stir well, and cool to room temperature.

[0034] The emulsification method is an oil-water phase method.

[0035] Example 12 Preparation method of Echeveria elegans oil cream 1) Oil phase preparation: Glyceryl monostearate, petrolatum, octadecanol and liquid paraffin are mixed and heated to 75-80℃ until completely melted; 2) Aqueous phase preparation: Mix Tween 80, sodium dodecyl sulfate, glycerol, and distilled water, and heat to 75-80 °C; 3) Emulsification: At 75 ℃ and a stirring speed of 1200 r / min, the aqueous phase is slowly added to the oil phase and stirred for 10 min while maintaining the temperature. 4) Adding medicine: Cool down to 40 ℃, add senna oil, stir well, and cool to room temperature.

[0036] The emulsification method is an oil-water phase method.

[0037] To verify the effectiveness of the invention, the inventive team conducted a series of experiments, as follows: I. Research on the Preparation Process of Echeveria elegans Oil Cream 1 Experimental Methods 1.1 Research on the molding process of Eau de Parfum Cream 1.1.1 Screening of Cream Base Formulation 1.1.1.1 Evaluation Methods and Scoring Criteria for Creams

[0038] The quality of Aina sesame oil cream was evaluated using a comprehensive scoring method, with indicators including appearance, texture, spreadability, stability, and centrifugation test.

[0039] Evaluation method: (1) Appearance characteristics: Examine whether the appearance, color and texture of the sample are uniform and delicate; (2) Fineness: Examine whether the sample has a uniform and fine texture, good roundness, and particle size; (3) Coating spreadability: Examine the consistency of the sample, its spreadability and whether it has a grainy feel; (4) Cold resistance stability: Weigh 2 g of each group of cream samples, label them and place them in a sealed container, put them in a refrigerator, set the temperature to -25 ℃, and take them out after 48 h. Observe the properties of the samples to see if there are any abnormal phenomena such as layering, bubbling, or clumping. (5) Heat resistance stability: Weigh 2 g of each group of cream samples, mark them and place them in a sealed container. Place them in a constant temperature oven with the temperature set at 60 ℃. After 48 h, take them out and cool them to room temperature. Observe the appearance of the samples to see if there are any abnormal phenomena such as layering, bubbling, or clumping. (6) Centrifugation stability: Weigh 2 g of each group of cream samples, place them in centrifuge tubes, seal them, and centrifuge at 7000 r / min. After 10 min, take them out and observe the characteristics of the samples to see if there are any abnormal phenomena such as layering, foaming, clumping, or water seepage.

[0040] 1.1.1.2 O / W type matrix design The dosages of stearic acid, glyceryl monostearate, petrolatum, octadecanol, liquid paraffin, Tween 80, triethanolamine, sodium lauryl sulfate, glycerol, and distilled water were investigated using a uniform analysis method, and the overall scores were calculated. See Table 2.

[0041]

[0042] 1.1.1.3 W / O type substrate design The dosages of stearic acid, glyceryl monostearate, petrolatum, beeswax, liquid paraffin, Tween 80, triethanolamine, Span 80, glycerol, and distilled water were investigated, and the overall scores were calculated. See Table 3.

[0043]

[0044] 1.1.2 Drug loading screening According to the optimal matrix formulation selected in Experiment 1, the oil phase composition was placed in a beaker and slowly heated to 75-80 ℃ until the oil phase was completely melted. While stirring, the aqueous phase was slowly added to the oil phase, and the mixture was stirred at 75-80 ℃ for 8-10 minutes. After naturally cooling to 40 ℃, different amounts of senna oil were added and stirred evenly. Then, heating was stopped and stirring was continued until completely cooled to obtain the final product. See Table 4.

[0045]

[0046] The cream was evaluated based on its appearance, smoothness, cold resistance, heat resistance, and centrifugation test according to the cream scoring standard, and a comprehensive score was calculated.

[0047] 1.1.3 Screening of Key Influencing Factors By examining multiple variables (such as the dosage of ingredients like glyceryl monostearate, Tween-80, and oil loading) at different levels, i.e., eliminating each component one by one and comparing the scores of different creams, the three factors that have the most significant impact on the quality of Aina sesame oil cream were preliminarily identified. See Table 5.

[0048]

[0049] The cream was evaluated based on its appearance, smoothness, cold resistance, heat resistance, and centrifugation test according to the cream scoring standard, and a comprehensive score was calculated.

[0050] 1.1.4 Optimization of Key Factor Ratios Using Response Surface Methodology By examining multiple variables at different levels, the three main factors affecting the quality of Aina sesame oil cream were initially identified as glyceryl monostearate, liquid paraffin, and sodium lauryl sulfate. This study will investigate these three factors, using 1 / 5 of the prescription amount for the experiment. The comprehensive score of the cream at three levels (high, medium, and low) for excipient dosage will be used as the evaluation index. The Design-Expert 13.0 software will be used for response surface methodology, and the test results will be analyzed. The experimental factors and their levels are shown in Table 6.

[0051]

[0052] The optimal molding process was selected using a 3-factor, 3-level design response surface methodology. The experimental design is shown in Table 7.

[0053]

[0054] 1.1.5 Optimization of preparation process parameters using orthogonal experimental design Besides the significant impact of the amount of matrix, emulsification temperature and emulsification time also have a considerable effect. Low emulsification temperature leads to incomplete emulsification, resulting in a rough ointment. High emulsification temperature reduces the emulsifying efficiency of the emulsifier, causing a decrease in ointment stability. Short emulsification time also leads to decreased ointment stability. Therefore, in orthogonal experiments, the composition of the aqueous and oil phases, emulsification temperature, and emulsification time are treated as variable factors for formulation and process verification.

[0055] L9(34) orthogonal experiments were conducted on emulsification temperature (70℃, 75℃, 80℃), emulsification time (5min, 10min, 15min), stirring speed (800r / min, 1000r / min, 1200r / min) and emulsification method (oil-water phase method, mixed heating method, post-addition of emulsifier method). The comprehensive score was used as the evaluation index. The orthogonal factors were evaluated as shown in Table 8.

[0056] 2 Experimental Results 2.1 Screening of Cream Matrix The matrix formula was determined to be: 5g glyceryl monostearate, 3g petrolatum, 2g octadecyl alcohol, 5g liquid paraffin, 2g Tween 80, 0.5g sodium lauryl sulfate, 6g glycerol, and 17g distilled water.

[0057] 2.2 Screening of drug loading capacity The optimal drug loading of the Aina sesame oil cream was determined to be 4.5g.

[0058] 2.3 Screening of the three factors that have the most significant impact on the quality of creams The results showed that groups 1, 4, and 6 had the lowest overall scores in the prescription. The three factors that had the most significant impact on the Aina sesame oil cream were identified as glyceryl monostearate, liquid paraffin, and sodium lauryl sulfate.

[0059] 2.4 Results of Response Surface Methodology Experiment The cream was evaluated for appearance, fineness, cold resistance, heat resistance, and centrifugation according to the cream scoring standard, and a comprehensive score was calculated. The total scores of each formula ranged from 34 to 42 points. Formulas in groups 14 and 16 had the highest comprehensive scores, indicating that they had better comprehensive performance under the experimental conditions. The experimental design results are shown in Table 9.

[0060]

[0061] Regression fitting analysis of the response surface methodology results was performed using Design Expert 13 software. The quadratic polynomial model equation between the overall score (Y) of the Aina sesame oil cream and the amounts of glyceryl monostearate (A), liquid paraffin (B), and sodium dodecyl sulfate (C) was obtained: Y = 41 + 0.25A - 0.125B + 0.625C + 0.25AB - 0.2500AC - 0.5BC - 3.5A² - 3.25B² - 2.25C². Variance results showed that p < 0.05 indicated a significant difference in the model; p > 0.05 indicated no significant difference in the lack-of-fit term; the coefficient of determination R² = 0.9493, indicating that the model could explain 94.93% of the response value variation, had a high goodness of fit, small experimental error, and could predict the molding process. The multivariate fitting results from the software are shown in Table 10.

[0062]

[0063] The three-dimensional response surface curves of the interaction of various factors are shown in the figure. Figure 1 Regression fitting analysis of the response surface methodology results using Design Expert 13 software yielded a quadratic polynomial model equation: Y = 41 + 0.25A - 0.125B + 0.625C + 0.25AB - 0.2500AC - 0.5BC - 3.5A² - 3.25B² - 2.25C². Variance results showed significant differences for p < 0.05; no significant differences for p > 0.05; and a coefficient of determination R² = 0.9493, indicating that the model could explain 94.93% of the response value variation, exhibiting high goodness of fit, small experimental error, and the ability to predict molding processes.

[0064] Box-Behnken response surface methodology revealed that all three factors significantly impacted the cream's quality. The interaction between glyceryl monostearate and sodium lauryl sulfate was the most pronounced, significantly affecting the cream's stability and texture. The amount of liquid paraffin primarily influenced the cream's spreadability and heat resistance. The optimal formulation was determined to be 5g glyceryl monostearate, 5g liquid paraffin, and 0.5g sodium lauryl sulfate. This combination resulted in a high overall score for the cream, demonstrating balanced performance and good practicality.

[0065] 2.5 Results of Orthogonal Experiments Through orthogonal experiments and evaluation of multiple indicators, the influence of each factor on the quality of the Aina sesame oil cream was determined to be in the following order: C. Stirring speed > A. Emulsification temperature > B. Emulsification time > D. Emulsification method. The optimal process combination is: A3B3C1D1, namely, emulsification temperature of 80℃, emulsification time of 15min, stirring speed of 800r / min, and oil-water phase method. The cream prepared under these conditions has the highest overall score, uniform appearance, good spreadability, and good heat resistance, cold resistance, and centrifugal stability, meeting the quality requirements of creams. The results of the orthogonal experiments and analysis of variance are shown in Table 11.

[0066]

[0067] 3. Conclusion This chapter examines the formulation and preparation process of angelica oil cream, determining the optimal matrix formulation, drug loading, and key process parameters. Using uniform design, response surface methodology, and orthogonal experiments, the optimal matrix formulation was selected as follows: 5g glyceryl monostearate, 3g petrolatum, 2g octadecanol, 5g liquid paraffin, 2g Tween-80, 0.5g sodium lauryl sulfate, 6g glycerol, and 17g distilled water, with an optimal drug loading of 4.5g. Based on this, response surface methodology identified glyceryl monostearate, liquid paraffin, and sodium lauryl sulfate as key factors affecting cream quality. A quadratic polynomial regression model was established to optimize the ratio of these three components to 5g, 5g, and 0.5g, respectively. Orthogonal experiments further clarified the optimal preparation process: emulsification temperature 80℃, emulsification time 15 min, stirring speed 800 r / min, and oil-water phase separation. The Aina sesame oil cream prepared using the optimized process has a uniform and delicate appearance, good spreadability, and meets the quality requirements for topical creams in terms of cold resistance, heat resistance, and centrifugal stability.

[0068] II. Pharmacological study of the effects of Erythrina variegata oil cream on deep second-degree burns in rats. 1 Experimental Methods 1.1 Preparation of Echeveria elegans oil cream The preparation method of the Aina sesame oil cream is the same as that in Chapter 1. The same ratio of water-in-oil (O / W) blank matrix is ​​used as the carrier. Aina sesame oil is added and mixed thoroughly (dosage concentration is 10%). It is stored at room temperature away from light for later use.

[0069] 1.2 Preparation of burn model The day before modeling, the fur on the backs of the rats was shaved. The rats were anesthetized with 1% sodium pentobarbital (40 mg / kg), and the skin surface was disinfected with 75% alcohol. Then, a burn instrument was used to apply the burns to the rat skin for 10 seconds, covering an area of ​​approximately 1 cm × 1 cm. The skin swelled and turned white, resulting in deep second-degree burns. During modeling, the rat skin was pulled up until a flat surface was formed to prevent damage to underlying organs, thus ensuring a uniform burn area. Each rat had two burns, one on each side.

[0070] 1.3 Experimental grouping and drug administration Rats were randomly divided into six groups: control group, model group, positive control group, aralia oil group, cream blank matrix group, and aralia oil cream group, with eight rats in each group. Control group: hair was shaved, no treatment was given; Model group: administered the same volume of physiological saline; Aralia oil group: administered the same volume of aralia oil; Positive control group, cream blank matrix group, and aralia oil cream group: administered the corresponding drug at a dose of 1 g / cm³. 2 After modeling, apply the corresponding medication twice daily, morning and evening. Clean the wound surface before administering the medication, and continue medication for 14 days.

[0071] 1.4 Rat Experimental Sample Collection Skin samples from the burn sites were fixed in 4% paraformaldehyde fixative 24 hours after the initial treatment for HE staining to determine the success of the model. Two groups of rats were sacrificed on days 7 and 14 after model establishment. The rats were weighed and anesthetized with 1% sodium pentobarbital (40 mg / kg). After complete anesthesia, the rats were fixed supine on the experimental table, and venous blood was collected via the abdominal main vein. After standing at room temperature, the blood was centrifuged at 3000 rpm for 12 min at 4 °C, and the supernatant was stored at -80 °C. Subsequently, a portion of the wound skin tissue was excised and preserved in 4% paraformaldehyde while maintaining a smooth surface. The remaining tissue was cleaned with PBS solution, flash-frozen in liquid nitrogen, and stored at -80 °C for later use.

[0072] 1.5 Observation of rat body shape and wound morphology The burn wounds of rats in each group were observed and recorded daily by the naked eye, including whether there was bruising and edema, whether scabs formed and fell off, epithelialization, etc. At the same time, the behavioral changes of rats after the model was established were recorded.

[0073] 1.6 Calculation of wound healing rate The day of model establishment was recorded as day 0. Subsequently, the healing of the skin wounds on the backs of the rats in each group was checked daily. Photographs of the burn wounds on days 0, 3, 7, 10, and 14 were taken and recorded. ImageJ software was used to plot the wound healing trajectory. The diameter of the skin wounds in each group was measured, and the burn wound healing rate at different time points was calculated (S0: wound area on day 0; Sn: wound area on day n).

[0074] 1.7 Histopathological Examination 1.7.1 Tissue embedding and section preparation Skin tissue from rats in each group was removed from the fixative and subjected to gradient elution. It was then sequentially immersed in 75% ethanol, 85% ethanol, and 95% ethanol for 1 hour each, followed by xylene:ethanol (1:1) for 30 minutes and xylene for 1 hour. After dehydration, the tissue was immersed in paraffin and embedded. After cooling, paraffin sections were prepared. Labeled paraffin blocks were frozen at -20°C, and 4μm thick sections were cut using a microtome. The sections were then spread flat on a 40°C warm water surface using a slide, retrieved, and labeled. The sections were then baked at 60°C for 1 hour to dry the moisture and melt the paraffin. After cooling, the sections were stored at room temperature for later use.

[0075] 1.7.2 HE staining The prepared sections were sequentially immersed in benzoyl peroxide I and benzoyl peroxide II for 10 min each, then in anhydrous ethanol I, anhydrous ethanol II, 95% ethanol, 85% ethanol, and 75% ethanol for 5 min each, followed by soaking in distilled water for 2 min to complete the dewaxing step. The sections were then immersed in hematoxylin staining solution for 5 min, rinsed with tap water for 20 s, differentiated in differentiation solution for 1 min, rinsed with tap water for 20 s, immersed in bluing solution for 5 min, rinsed with tap water for 20 s, stained with eosin solution for 1 min, and rinsed with distilled water for 3 s. After completing the above steps, the sections were again immersed in 75% ethanol, 85% ethanol, and 95% ethanol for 3 s each, anhydrous ethanol I and anhydrous ethanol II for 1 min each, and benzoyl peroxide I and benzoyl peroxide II for 30 s each. After the sections were air-dried, they were mounted with neutral resin for optical microscope observation and image acquisition.

[0076] 1.8 Statistical Analysis Data analysis was performed using SPSS 26.0 software, and the results are presented in... +s indicates statistical significance. One-way ANOVA is used when multiple data sets are normally distributed and have homogeneous variances, with the Least Significant Difference (LSD) test used for pairwise comparisons between groups. Non-parametric tests are used when the data are not normally distributed or have heterogeneous variances. P < 0.05 indicates statistical significance.

[0077] 2 Experimental Results 2.1 Morphological observation and analysis of burn wounds like Figure 2 As shown, after burns, the skin wounds of rats immediately turned grayish-white, smooth, and edematous, clearly distinguishing the burned and unburned areas. Skin elasticity decreased, while toughness increased. Rats in all groups showed lethargy and reduced appetite after burns. On days 1-2, edema subsided and the wounds gradually hardened in the Aina sesame oil cream group; rats in the positive control group still had slight edema and whitish wounds; rats in the model group, blank matrix group, and Aina sesame oil group showed significant edema and grayish-white wounds. On day 3, most rats in the Aina sesame oil cream group began to scab over their wounds; the wounds in the positive control group darkened, edema completely subsided, and some scabs formed; the wounds in the model group, blank matrix group, and Aina sesame oil group remained grayish-white. On day 7, most rats in the Aina sesame oil cream group had their scabs fall off, revealing new granulation tissue on the wounds; some rats in the positive control group also began to scab off; the model group, blank matrix group, and Aina sesame oil group did not scab off. On day 14, all rats in the Aina sesame oil cream group had completed scab removal and the wounds were basically healed; most rats in the positive drug group began to scab and the wounds gradually healed; most rats in the model group had thick scabs with rough and dry surfaces and no scab removal was observed; only a small number of rats in the blank matrix group and the Aina sesame oil group began to scab, and the healing process was significantly delayed.

[0078] like Figure 3 , Figure 4 The results showed that the healing progress of the angelica oil group and the angelica oil cream group was superior to that of the model group and the blank matrix group at all observation time points, exhibiting faster wound contraction and tissue regeneration trends. Among them, the healing trajectory of the angelica oil cream group was the most ideal and better than that of the positive drug group, indicating that it has good healing-promoting activity.

[0079] During the experiment, it was found that after administration of the safflower oil to rats, significant dryness, peeling, and even cracking of the skin around the burn wounds on their backs were observed. This indicates that direct absorption of safflower oil can cause some skin irritation, leading to dehydration. However, rats in the safflower oil cream group did not exhibit such adverse skin reactions; their skin around the wounds remained relatively intact and moist. This demonstrates that formulating safflower oil into a cream effectively encapsulates, sustains, and moisturizes the skin, improving its healing-promoting effects while enhancing the safety of the medication.

[0080] 2.6 Histopathological examination like Figure 5On day 7, the control group showed clear skin tissue structure, a thinner epidermis, neatly arranged cells, regular collagen fibers in the dermis, and no obvious inflammatory cell infiltration. The model group showed more inflammatory exudate, significant granulation tissue proliferation, thickened epidermis, disordered collagen fibers in the dermis, and obvious inflammatory cell infiltration. The positive drug group showed less epidermal thickening, less dermal inflammatory infiltration, and more regular collagen fibers compared to the model group. The Aina sesame oil group and the blank matrix group showed less epidermal thickening, less dermal inflammatory infiltration, and less disordered collagen fibers compared to the model group. The Aina sesame oil cream group showed no significant epidermal thickening, less dermal inflammatory infiltration, more regular collagen fiber arrangement, and a tissue structure close to that of the normal group.

[0081] On day 14, the control group showed intact skin structure, thin epidermis, regular arrangement of dermal collagen fibers, and no inflammatory cell infiltration. The model group still had a small amount of inflammatory exudate, significant granulation tissue proliferation, thickened epidermis, disordered arrangement of dermal collagen fibers, and still significant inflammatory infiltration. The positive drug group showed that the epidermal thickness had basically recovered, dermal inflammatory infiltration had significantly decreased, and collagen fibers were arranged regularly. The epidermal thickening in the Aina sesame oil group and the blank matrix group was significantly reduced compared to day 7, dermal inflammatory infiltration was reduced, and collagen fiber arrangement tended to be regular. The epidermal thickness in the Aina sesame oil cream group was close to that of the control group, the dermal collagen fibers were arranged regularly, no obvious inflammatory cell infiltration was observed, the wound repair was good, and the histological appearance was similar to that of the control group.

[0082] 2.7 ELISA detection of inflammatory factors The serum levels of IL-1β, IL-6, and TNF-α in rats of each group were detected by ELISA at 7 and 14 days after treatment. The results are as follows: Figure 6 , Figure 7 , Figure 8 As shown.

[0083] Compared with the control group, the levels of the three inflammatory factors in the model group rats were significantly increased at all time points (P<0.01), indicating that the inflammation model was successfully established. Compared with the model group, the levels of inflammatory factors in the positive drug group, the aralia oil group, and the aralia oil cream group were decreased at all time points. Among them, the levels of IL-1β, IL-6, and TNF-α in the positive drug group were lower than those in the model group at 7 and 14 days, and the differences were statistically significant (P<0.05). The levels of inflammatory factors in the aralia oil group were also lower than those in the model group at 7 and 14 days, but the decrease in IL-6 and TNF-α at 14 days was slightly smaller than that at 7 days. There was no significant difference between the blank matrix group and the model group (P>0.05), indicating that the blank matrix itself has no anti-inflammatory activity. The levels of each inflammatory factor in the aralia oil cream group were slightly lower than those in the model group at 7 days, but were close to those in the model group at 14 days. Its anti-inflammatory effect was not as good as that of the aralia oil group, which may be related to the dosage form affecting drug release or absorption. See Tables 12 and 13.

[0084]

[0085]

[0086] 3. Conclusion This invention evaluates the repair effect and possible mechanism of scald ointment on burn wounds by establishing a rat model of deep second-degree burns.

[0087] Pharmacodynamic results showed that the linalool oil cream significantly promoted wound healing. On days 7 and 14 after administration, its wound healing rate was superior to that of the model group, the blank matrix group, and the linalool oil group, and the healing effect was comparable to that of the positive drug group. Morphological observation and healing trajectory analysis of the wound indicated that the cream could accelerate scab formation, scab shedding, and granulation tissue regeneration.

[0088] Histopathological results showed that the epidermal thickening of rats in the aralia oil cream group was not significant, inflammatory infiltration in the dermis was reduced, collagen fiber arrangement was more regular, and the tissue structure was closer to that of the normal control group. Regarding safety, the aralia oil cream did not cause adverse reactions such as dry skin or desquamation around the wound during treatment, while the aralia oil-only group showed significant skin irritation, indicating that the cream formulation effectively moisturizes while maintaining stable drug release. ELISA results showed that the cream could reduce serum IL-1β, IL-6, and TNF-α levels to a certain extent, suggesting that its healing-promoting effect may be related to the regulation of the inflammatory response.

[0089] Although the present invention has been described in detail above with general descriptions, specific embodiments, and experiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. A cream made from angelica oil, characterized in that, It consists of the following components in parts by weight: Active ingredient: 4.5 parts of Ebony oil; Oil phase components: 3-7 parts glyceryl monostearate, 3 parts petrolatum, 2 parts octadecanol, 3-7 parts liquid paraffin; Emulsifier: 2 parts Tween 80, 0.3-0.7 parts sodium dodecyl sulfate; Aqueous phase components: 6 parts glycerol, 17 parts distilled water; The cream is an O / W type with a drug loading of 10%.

2. The anointing oil cream according to claim 1, characterized in that, 5-7 parts of the glyceryl monostearate; 5-7 parts of the liquid paraffin; 0.5-0.7 parts of the sodium dodecyl sulfate.

3. The anointing oil cream according to claim 2, characterized in that, 5 parts of the glyceryl monostearate; 5 parts of the liquid paraffin; 0.5 parts of the sodium dodecyl sulfate.

4. A method for preparing the senna oil cream as described in any one of claims 1-3, characterized in that, Includes the following steps: 1) Oil phase preparation: Glyceryl monostearate, petrolatum, octadecanol, and liquid paraffin are mixed and heated to 75-80 ℃ until completely melted; 2) Aqueous phase preparation: Mix Tween 80, sodium dodecyl sulfate, glycerol, and distilled water, and heat to 75-80 ℃; 3) Emulsification: At 70-80 ℃ and a stirring speed of 800-1200 r / min, the aqueous phase is slowly added to the oil phase, and the mixture is kept warm and stirred for 5-15 min. 4) Adding medicine: Cool down to 40 ℃, add senna oil, stir well, and cool to room temperature.

5. The preparation method according to claim 4, characterized in that, The emulsification method is oil-water phase separation.

6. The preparation method according to claim 4, characterized in that, The emulsification described in step 3) is as follows: at 75-80 ℃ and a stirring speed of 800-1000 r / min, the aqueous phase is slowly added to the oil phase and stirred for 10-15 min while maintaining the temperature.

7. The preparation method according to claim 6, characterized in that, The emulsification described in step 3) is as follows: at 80 °C and a stirring speed of 800 r / min, the aqueous phase is slowly added to the oil phase and stirred for 15 min while maintaining the temperature.

8. The use of the anointing oil cream as described in any one of claims 1-3 in the preparation of a medicine for treating deep second-degree burns.

Images