Lavender oil preparation for promoting healing of skin wounds of animals and its preparation method

Abstract

This invention relates to a lavender essential oil preparation for promoting animal skin wound healing and its preparation method. The invention belongs to the field of veterinary drug preparation technology. The purpose of this invention is to provide veterinary clinics with a lavender essential oil preparation and its preparation method that is simple to produce, water-soluble, stable, safe, has a strong effect on promoting animal skin wound healing, and is convenient for clinical use. The lavender essential oil preparation for promoting animal skin wound healing is prepared from the following raw materials in parts by weight: 0.76–12.45 parts by weight of lavender essential oil, 15–37.24 parts by weight of castor oil polyoxyethylene ether 40, 0–11.15 parts by weight of 1,2-propanediol, 41.43–62 parts by weight of distilled water, and 10–30 parts by weight of Bailingjinfang (a traditional Chinese medicine). This invention has the effect of promoting animal skin wound healing, significantly improving the wound healing rate, and thus shortening the wound healing time. It is a topical medicine for animal skin wounds. The raw materials of this invention are readily available, the production process is simple, the production cost is low, the stability is good, it is easy to store, and it is suitable for large-scale production.

Description

Technical Field

[0001] This invention belongs to the field of veterinary drug formulation technology, specifically relating to a lavender essential oil formulation that promotes the healing of animal skin wounds and its preparation method. Background Technology

[0002] Skin trauma is a common injury in animal husbandry and a frequent surgical condition in veterinary clinics, and it is prone to infection. When infection occurs, if the pathogens at the wound site exhibit varying degrees of drug resistance, treatment becomes more difficult, wounds heal slowly or for extended periods, and animal suffering increases. Therefore, it is clinically necessary to promptly administer an anti-infective drug with wound-healing properties to the animal's skin wound to improve healing efficiency.

[0003] Lavender essential oil is a pure natural plant extract, widely used in various fields due to its high volatility, small molecular size, and easy absorption. In recent years, with the discovery of its antibacterial, bactericidal, antiviral, anti-inflammatory, sedative, and hypnotic effects, lavender essential oil has seen increasing applications in the pharmaceutical field, especially given the growing antibiotic resistance of bacteria. Lavender essential oil holds promise as a natural antibacterial agent to alleviate the antibiotic crisis. Data shows that lavender essential oil not only has strong bactericidal effects against many bacterial strains, such as Staphylococcus aureus and Enterococcus faecalis, but also helps relieve skin inflammation and promote wound healing. Therefore, lavender essential oil holds promise for development as an anti-infective and wound-healing drug. However, its volatility, poor water solubility, poor stability, easy oxidation of active ingredients, and low bioavailability limit its clinical dosage form development and widespread application. Summary of the Invention

[0004] The invention aims to solve the aforementioned problems of lavender essential oil and provide veterinary clinics with a lavender essential oil preparation and its preparation method that is simple to produce, has good water solubility, is stable and safe, has a strong effect on promoting the healing of animal skin wounds, and is convenient for clinical use.

[0005] The technical solution of the present invention is a lavender essential oil preparation for promoting the healing of animal skin wounds, characterized in that it is prepared from the following raw materials in parts by weight: 0.76-12.45 parts by weight of lavender essential oil, 15-37.24 parts by weight of castor oil polyoxyethylene ether 40 (EL-40), 0-11.15 parts by weight of 1,2-propanediol, 41.43-62 parts by weight of distilled water, and 10-30 parts by weight of Bailing Jinfang.

[0006] EL-40 is a pharmaceutical excipient and a nonionic, highly efficient solubilizer that improves the solubility and bioavailability of poorly soluble substances. It is readily soluble in water, fatty acids, and other organic solvents, and possesses excellent emulsifying properties. In the preparation of O / W formulations, it can be used for the emulsification of various vegetable oils, animal oils, and mineral oils.

[0007] 1,2-Propanediol, glycerol, and n-Butanol are all commonly used pharmaceutical excipients in the pharmaceutical industry. 1,2-Propanediol is an important pharmaceutical solvent, widely used in pharmaceutical formulations, drug delivery systems, and other applications due to its excellent solubility, low toxicity, and high stability. Its good viscosity and hygroscopicity make it widely used as a humectant, antifreeze, lubricant, and solvent in the pharmaceutical, food, and cosmetic industries.

[0008] Bailing Jinfang is an antibacterial powder that inhibits the growth of common bacteria such as Staphylococcus aureus, Escherichia coli, and Candida albicans, and is suitable for skin antibacterial use.

[0009] A method for preparing a lavender essential oil preparation that promotes the healing of animal skin wounds, characterized by comprising the following steps:

[0010] (1) Weigh out lavender essential oil, EL-40, 1,2-propanediol, distilled water and Bailingjinfang respectively according to the weight parts, and set aside.

[0011] (2) At room temperature, first mix lavender essential oil, EL-40 and 1,2-propanediol, then slowly add the prescribed amount of distilled water while stirring constantly to form a clear and transparent emulsion.

[0012] (3) Add the prescribed amount of Bailingjinfang to the above emulsion and dissolve it completely to obtain the lavender essential oil preparation for promoting animal skin wound healing as described in this invention.

[0013] The lavender essential oil preparation prepared by this invention is an oil-in-water (O / W) emulsion with a particle size of 1–100 nm. Its concentration can be adjusted by adding any proportion of distilled water as needed, which is convenient for production and use.

[0014] The lavender essential oil preparation of the present invention has the effect of promoting the healing of animal skin wounds, and can significantly improve the wound healing rate of animals, thereby shortening the wound healing time.

[0015] The lavender essential oil preparation of this invention is suitable for promoting the healing of animal skin wounds and is a topical medicine for skin wounds.

[0016] The present invention has the following beneficial effects:

[0017] (1) This invention can significantly enhance the wound healing effect of lavender essential oil, effectively shorten the time required for animal skin wounds to heal, reduce secondary infection of wounds, effectively alleviate animal pain, and can be widely used in various animal skin injuries.

[0018] (2) The present invention uses EL-40 and / or 1,2-propanediol to disperse lavender essential oil into O / W type small droplets with a particle size of 1 to 100 nm, so that the essential oil is surrounded by water, which not only increases the solubility of lavender essential oil and solves the problem that lavender essential oil is difficult to dissolve in water, but also improves its stability and tissue penetration of the medicine.

[0019] (3) The present invention has good dilution properties. In clinical applications, the lavender essential oil preparation can be diluted to the required concentration by adding distilled water in any proportion as needed, which is convenient to use.

[0020] (4) The raw materials of the lavender essential oil preparation for promoting animal skin wound healing of the present invention are readily available, the production process is simple, the production cost is low, the stability is good, the storage is easy, and the production is convenient for large-scale production. Attached Figure Description

[0021] Figure 1 The image shows a transmission electron microscope (TEM) image of the lavender essential oil preparation for promoting animal skin wound healing, prepared using the formulation and process described in Example 1 below.

[0022] Figure 2 The particle size distribution diagram shows the lavender essential oil preparation for promoting animal skin wound healing, prepared using the formulation and process described in Example 1 of this invention.

[0023] Figure 3 A bar chart showing the skin wound healing rate of mice in each group at different treatment times. Detailed Implementation

[0024] The following examples are mainly used to further illustrate the present invention:

[0025] Example 1

[0026] (1) Weigh out 8.57 g of lavender essential oil, 15 g of EL-40, 5 g of 1,2-propanediol and 41.43 g of distilled water, and 30 g of Bailing Jinfang, respectively, for later use.

[0027] (2) At room temperature, first mix lavender essential oil, EL-40 and 1,2-propanediol, then slowly add distilled water while stirring constantly to form a clear and transparent emulsion.

[0028] (3) Add the prescribed amount of Bailingjinfang to the above emulsion and dissolve it completely to obtain the lavender essential oil preparation with a particle size of 1 to 100 nm and a clear and uniform appearance as described in this invention.

[0029] Example 2

[0030] (1) Weigh out 12.45 g of lavender essential oil, 29.05 g of EL-40 and 58.50 g of distilled water respectively, and set aside.

[0031] (2) At room temperature, first mix lavender essential oil and EL-40, then slowly add distilled water and stir continuously to form a clear and transparent emulsion, thus obtaining the lavender essential oil preparation with a particle size of 1 to 100 nm and a clear and uniform appearance as described in this invention.

[0032] Example 3

[0033] (1) Weigh out 0.76 g of lavender essential oil, 37.24 g of EL-40 and 62 g of distilled water respectively, and set aside.

[0034] (2) At room temperature, first mix lavender essential oil and EL-40, then slowly add distilled water and stir continuously to form a clear and transparent emulsion, thus obtaining the lavender essential oil preparation with a particle size of 1 to 100 nm and a clear and uniform appearance as described in this invention.

[0035] Example 4

[0036] (1) Weigh out 0.91 g of lavender essential oil, 33.44 g of EL-40, 11.15 g of 1,2-propanediol, 44.50 g of distilled water, and 10 g of Bailing Jinfang, respectively, and set aside.

[0037] (2) At room temperature, first mix lavender essential oil, EL-40 and 1,2-propanediol, then slowly add distilled water while stirring constantly to form a clear and transparent emulsion.

[0038] (3) Add the prescribed amount of Bailingjinfang to the above emulsion and dissolve it completely to obtain the lavender essential oil preparation with a particle size of 1 to 100 nm and a clear and uniform appearance as described in this invention.

[0039] Example 5

[0040] (1) Weigh out 6.46 g of lavender essential oil, 25.84 g of EL-40, 52.70 g of distilled water, and 15 g of Bailing Jinfang, respectively, and set aside.

[0041] (2) At room temperature, first mix lavender essential oil and EL-40, then slowly add distilled water while stirring constantly to form a clear and transparent emulsion.

[0042] (3) Add the prescribed amount of Bailingjinfang to the above emulsion and dissolve it completely to obtain the lavender essential oil preparation with a particle size of 1 to 100 nm and a clear and uniform appearance as described in this invention.

[0043] Example 6

[0044] (1) Weigh out 6.27 g of lavender essential oil, 18.81 g of EL-40, 6.27 g of 1,2-propanediol, 48.65 g of distilled water, and 20 g of Bailing Jinfang, respectively, and set aside.

[0045] (2) At room temperature, first mix lavender essential oil, EL-40 and 1,2-propanediol, then slowly add distilled water while stirring constantly to form a clear and transparent emulsion.

[0046] (3) Add the prescribed amount of Bailingjinfang to the above emulsion and dissolve it completely to obtain the lavender essential oil preparation with a particle size of 1 to 100 nm and a clear and uniform appearance as described in this invention.

[0047] To further illustrate the specific effects of the present invention, experimental examples are used below for verification.

[0048] Experimental Example 1: Screening of Solubilizers

[0049] The solubilizers for lavender essential oil preparations were screened based on the highest content of lavender essential oil in the system, as exemplified in Example 1.

[0050] At room temperature, 8.57 g of lavender essential oil, 15 g of EL-40, 5 g of 1,2-propanediol, 41.43 g of distilled water, and 30 g of Bailingjinfang were weighed out and set aside. First, the lavender essential oil, EL-40, and 1,2-propanediol were mixed evenly, and then distilled water was slowly added while stirring continuously to form a clear and transparent emulsion. Then, the prescribed amount of Bailingjinfang was added to the above emulsion and dissolved completely to obtain the lavender essential oil preparation with a particle size of 1-100 nm and a clear and uniform appearance as described in this invention. Using the same method, EL-40 was replaced with the same mass of Tween 80 and polyoxyethylene 40 hydrogenated castor oil (PEG-40) to observe whether a lavender essential oil preparation could be formed. The results are shown in Table 1, and EL-40 was selected as a solubilizer.

[0051] Table 1. Screening test results of EL-40

[0052]

[0053] Note: "√" indicates that a clear and uniform lavender essential oil preparation can be formed, and "×" indicates that it is cloudy.

[0054] Experimental Example 2: Identification of the structural type of lavender essential oil preparations

[0055] Identification was performed using a staining method. The structural type of the formulation was determined by the diffusion rate of the water-soluble dye methylene blue and the oil-soluble dye Sudan III within the formulation. If the diffusion rate of methylene blue was greater than that of Sudan III, the prepared formulation was of the oil-in-water (O / W) type; otherwise, it was of the water-in-oil (W / O) type. The results showed that the formulation of the present invention was of the O / W type.

[0056] Experimental Example 3: Microscopic morphological observation of lavender essential oil preparations

[0057] Taking Example 1 as an example, the microstructure of the formulation was observed using transmission electron microscopy. 5 μL of the formulation was dropped onto a copper grid coated with a carbon film. After air-drying, a 2% phosphotungstic acid solution was dropped onto the copper grid for negative staining. After air-drying, the microstructure of the formulation was observed under a transmission electron microscope. Observation results ( Figure 1 This indicates that the droplets in lavender essential oil preparations are spherical and evenly distributed.

[0058] Experimental Example 4: Determination of Particle Size of Lavender Essential Oil Preparations

[0059] An appropriate amount of the formulation from Example 1 was taken, and its average particle size was determined using a laser particle size analyzer. The particle size analysis results ( Figure 2 The results showed that the average droplet size of the lavender essential oil preparation was 16.09 nm and the polydispersity index was 0.069.

[0060] Example 5: Stability Study of Lavender Essential Oil Preparations

[0061] The stability of lavender essential oil preparations was preliminarily investigated using centrifugation. Samples were placed at 4℃, 25℃, and 40℃ for 0, 30, 60, 90, and 180 days, respectively, and then centrifuged at 12,000 r / min for 20 min. The appearance changes of the lavender essential oil preparations before and after centrifugation were observed, including whether precipitation, layering, or turbidity occurred. The results (see Table 2) indicate that the lavender essential oil preparations have good stability.

[0062] Table 2. Results of stability study of lavender essential oil preparations

[0063]

[0064] Example 6: Safety Evaluation of Lavender Essential Oil Preparations

[0065] The safety of lavender essential oil preparations was evaluated using skin sensitization tests.

[0066] Eighteen rabbits were randomly divided into three groups: a negative control group, a positive control group, and a lavender essential oil preparation group, with six rabbits in each group (half male and half female). Twenty-four hours before the experiment, hair was removed from both sides of the rabbits' spine using an electric razor, with a removal area of ​​5 cm × 10 cm on each side. The negative control group received direct application of physiological saline; the positive control group received direct application of the sensitizing agent (2,4-dinitrochlorobenzene); and the lavender essential oil preparation group received direct application of an 8% lavender essential oil preparation.

[0067] Administration method:

[0068] (1) Sensitizing contact

[0069] In the negative control group, 0.5 mL of physiological saline was evenly applied to the left side of the bald area of ​​rabbits. In the positive control group, 0.5 mL of 1% 2,4-dinitrochlorobenzene sensitizer was evenly applied to the left side of the bald area of ​​rabbits. In the lavender essential oil preparation group, 0.5 mL of 8% lavender essential oil preparation was evenly applied to the left side of the bald area of ​​rabbits. The bald areas of all groups were covered with sterile, non-irritating gauze and plastic wrap, and then secured with medical tape. Six hours after administration, the gauze and plastic wrap were removed, and any residual drug was wiped away with warm water. The same method was used to administer the drug once on days 7 and 14, for a total of three administrations.

[0070] (2) Stimulate contact

[0071] Fourteen days after the last sensitization test (out of a total of 28 days), 0.5 mL each of physiological saline, 0.1% 2,4-dinitrochlorobenzene sensitizer, and 8% lavender essential oil preparation were applied to the right side of the bald area of ​​rabbits in the negative control group, positive control group, and lavender essential oil preparation group. The areas were then covered with sterile, non-irritating gauze and plastic wrap, and secured with medical tape. Six hours after administration, the gauze and plastic wrap were removed, and residual medication was wiped away with warm water. Skin allergic reactions were immediately observed, and again at 24, 48, and 72 hours after medication removal.

[0072] Results evaluation: The skin allergy reaction scores of each experimental group of animals were evaluated according to the skin sensitization reaction severity scoring standard and the skin sensitization evaluation standard. The sensitization reaction incidence rate and the average reaction were calculated according to the formulas: Sensitization reaction incidence rate (%) = (number of animals with erythema + edema) / total number of test animals × 100% and average reaction rate = (total score for erythema formation + total score for edema formation) / total number of animals.

[0073] The results of the skin sensitization test of lavender essential oil preparations are shown in Tables 3 and 4. In both the lavender essential oil preparation group and the negative control group, no rabbits showed erythema or edema or other allergic reactions, and no rabbits died. The average sensitization score was 0, and the sensitization rate was 0. In the positive control group, all rabbits showed varying degrees of erythema or edema allergic reactions within 24–72 hours after administration, with an average sensitization score between 2.6 and 5.4, and a sensitization rate of 100%, but no rabbits died. The results indicate that lavender essential oil preparations do not cause skin sensitization and are safe.

[0074] Table 3. Skin allergy reaction scores of experimental animals in each group (n=6)

[0075]

[0076] Table 4. Sensitization rate of lavender essential oil preparations on rabbit skin

[0077]

[0078] Experimental Example 7: Wound Healing Effect of Lavender Essential Oil Preparations

[0079] Taking Example 1 as an example, the wound-healing effect of lavender essential oil preparation was studied.

[0080] (1) Effects of lavender essential oil preparations on skin wound healing in mice

[0081] ① Grouping and administration of experimental animals

[0082] Mice were randomly divided into six groups: a negative control group, a positive control group, a high-dose lavender essential oil preparation group (8%), a medium-dose lavender essential oil preparation group (4%), a low-dose lavender essential oil preparation group (2%), and a lavender essential oil group (8%), with 25 mice in each group. A control group was also included.

[0083] The negative control group received 0.1 mL of physiological saline evenly, the positive control group received 0.1 g of Jingwanhong ointment evenly, the high, medium, and low dose lavender essential oil preparation groups received 0.1 mL of 8%, 4%, and 2% lavender essential oil preparations evenly, respectively, and the lavender essential oil group received 0.1 mL of 8% lavender essential oil evenly. All groups received the medication twice daily at 9:00 AM and 6:00 PM for 14 consecutive days.

[0084] ② Determination of skin wound healing rate in mice

[0085] After establishing the mouse skin wound model, the mouse wounds were photographed on days 0, 3, 5, 7, 10, and 14 of treatment. The wound area and skin wound healing rate of the mice were calculated using ImageJ image analysis software, and statistical analysis was performed using SPSS software.

[0086] ③ Test Results

[0087] Results of skin wound healing rates at different treatment times in each group of mice are shown below. Figure 3 Compared with the positive control group, the 8% lavender essential oil preparation group showed a significant difference on day 3 of treatment (P<0.05), and highly significant differences on days 7, 10, and 14 (P<0.01); the 4% lavender essential oil preparation group showed highly significant differences on days 7 and 10 of treatment (P<0.01), but no significant differences on days 3, 5, and 14 (P>0.05); the 2% lavender essential oil preparation group showed highly significant differences on days 5, 7, 10, and 14 of treatment (P<0.01). These results indicate that lavender essential oil preparations promote wound healing in animals, and their therapeutic effect on mouse wounds increases with increasing drug concentration. Furthermore, the 8% lavender essential oil preparation showed a superior wound healing effect compared to the positive control group. Compared with the 8% lavender essential oil group, the 8% lavender essential oil preparation group showed significant differences on days 3 and 5 of treatment (P<0.05), and highly significant differences on days 7, 10, and 14 (P<0.01). The results indicate that lavender essential oil promotes wound healing in animals, and the preparation of lavender essential oil significantly enhances its wound-healing effect, significantly improves the wound healing rate, and thus shortens the wound healing time.

[0088] (2) Observation on the therapeutic effect of lavender essential oil preparations on skin wounds in dogs and cats

[0089] In an animal hospital, an 8% lavender essential oil preparation was used to treat various skin wounds in dogs and cats. Treatment outcomes (healed, effective, and ineffective) were recorded, and the results are shown in Table 5. The healing and effective rates for skin wounds in dogs were both 100%, with an ineffective rate of 0%, resulting in a total effective rate of 100%. The healing and effective rates for skin wounds in cats were both 100%, with an ineffective rate of 0%, resulting in a total effective rate of 100%.

[0090] Table 5. Therapeutic effect of 8% lavender essential oil preparation on skin wounds in dogs and cats (%)

[0091]

[0092] Experimental Example 8: Effect of Bailing Jinfang on the wound-healing effect of lavender essential oil preparations

[0093] Taking Example 2 as an example, the lavender essential oil preparation without the addition of Bailingjinfang was used in a safety test on rabbit skin wounds. The results are shown in Tables 6 and 7. The test results show that the lavender essential oil preparation without the addition of Bailingjinfang is safe for rabbit skin wounds and has a certain wound healing promoting effect.

[0094] Table 6 Single Dosage of Lavender Essential Oil Preparations Without Bailingjinfang

[0095] Results of irritation test on rabbit skin

[0096]

[0097] Table 7. Repeated administration of lavender essential oil preparations without the addition of Bailingjinfang.

[0098] Results of irritation test on rabbit skin

[0099]

[0100] Taking the effects of lavender essential oil preparations on skin wound healing in Examples 1 and 7(1) as examples, after adding Bailing Jinfang to prepare lavender essential oil preparations, compared with the same concentration of lavender essential oil group, its wound healing promotion effect was significantly different on the 3rd and 5th days of treatment (P<0.05), and extremely significant after the 7th day (P<0.01), as shown in Table 8. The results show that Bailing Jinfang can significantly enhance the wound healing promotion effect of lavender essential oil preparations through its antibacterial effect. Data shows that Bailing Jinfang inhibits the growth of Staphylococcus aureus, Escherichia coli, and Candida albicans. On the other hand, a large amount of data shows that lavender essential oil has antibacterial, antiviral, antifungal, and anti-inflammatory pharmacological activities. The combined application of lavender essential oil and Bailing Jinfang can effectively inhibit microbial infection at the skin wound site, enhance the wound healing promotion effect of lavender essential oil, thereby accelerating the healing speed of skin wounds and shortening the time required for wound healing.

[0101] Table 8 Skin wound healing rate of mice in different treatment times

[0102]

[0103] Note: Different letters in each column represent statistically significant differences, a~b (P<0.05), A~D (P<0.01).

Claims

1. A lavender essential oil preparation for promoting wound healing in animals, characterized in that: It is prepared from the following raw materials in parts by weight: 0.76 to 12.45 parts by weight of lavender essential oil, 15 to 37.24 parts by weight of castor oil polyoxyethylene ether, 0 to 11.15 parts by weight of 1,2-propanediol, 41.43 to 62 parts by weight of distilled water, and 10 to 30 parts by weight of Bailing Jinfang. Its preparation method includes the following steps: (1) Weigh out lavender essential oil, castor oil polyoxyethylene ether 40, 1,2-propanediol, distilled water and Bailingjinfang respectively according to the weight parts, and set aside; (2) At room temperature, first mix lavender essential oil, castor oil polyoxyethylene ether 40 and 1,2-propanediol, then slowly add the prescribed amount of distilled water while stirring constantly to form a clear and transparent emulsion; (3) Add the prescribed amount of Bailingjinfang to the above emulsion and stir until completely dissolved to obtain the lavender essential oil preparation that promotes the healing of animal skin wounds.

2. The lavender essential oil preparation for promoting wound healing in animals as described in claim 1, characterized in that: The formulation is an oil-in-water emulsion with a particle size of 1–100 nm.

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