A tetrapod-shaped zinc oxide whisker preparation for treating burns and a preparation method thereof

Abstract

The application discloses a four-needle-shaped zinc oxide whisker preparation for scald treatment and a preparation method thereof. The raw materials of the composition include 5-15 parts of lavender essential oil, 1-5 parts of four-needle-shaped zinc oxide whisker, 5-20 parts of white radix angelicae pubescentis and radix et rhizoma rhei extract and 1 part of borneol in terms of weight. The spray film preparation has the effects of antibacterial and anti-inflammatory, heat-clearing and detoxifying, swelling and pain relieving and the like by reasonable formula, can promote scald tissue repair for various symptoms caused by scald, and is convenient to use and easy to be accepted by patients.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine development, specifically to a four-needle-shaped zinc oxide whisker preparation for the treatment of burns and its preparation method. Background Technology

[0002] Burns are tissue injuries caused by hot liquids, flames, hot metals, steam, high-temperature gases, electrical energy, chemicals, radiation, etc., and are an extremely complex traumatic disease. After a burn, the skin loses its normal protective barrier, the wound is exposed, fluids leak out, the wound is extremely painful, and secondary infections are highly likely. Therefore, taking active measures in the early stages to control the burn condition, promote wound healing, and prevent subsequent secondary infections is crucial. Western medicine treats burns primarily with antibiotics, but with inappropriate use of antibiotics and the increase in drug-resistant bacteria, the treatment effect has gradually weakened. Traditional Chinese medicine has a long history of treating burns; both "Qianjin Fang" and "Wai Ke Zheng Zong" record treatments for burns. Currently, most commercially available Chinese medicine preparations are ointments, such as Jingwanhong Burn Ointment, which has good anti-inflammatory and tissue-regenerating effects. However, ointments have drawbacks such as poor breathability, which is not conducive to wound application, and some patients may experience sulfonamide allergic reactions. Therefore, it is necessary to develop various dosage forms to promote the development of Chinese medicine in burn treatment.

[0003] Tetranexamic zinc oxide whiskers are the only whiskers in the whisker family with a three-dimensional structure. The four whiskers extend in three dimensions, forming a tetrahedral structure. Their tips are at the nanoscale, and their nano-active components can effectively kill and remove bacteria and debris, while also decomposing toxins secreted by bacteria, exhibiting significant antibacterial effects. However, monomeric tetranexamic zinc oxide whiskers have poor solubility, being difficult to dissolve in water and ethanol, and their application in the pharmaceutical field is limited. Lavender, belonging to the genus *Lavender* of the Lamiaceae family, contains volatile oils, flavonoids, phenylpropanoids, etc. Studies have shown that lavender essential oil has good antibacterial effects, exhibiting strong inhibitory effects against *Staphylococcus aureus* and other bacteria. Lavender essential oil also has a good therapeutic effect on local burns. However, lavender essential oil is highly soluble and volatile, making direct application difficult to achieve therapeutic effects. There is an urgent need to develop suitable formulations to enhance the medicinal effects of lavender essential oil. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a composition containing tetra-needle-shaped zinc oxide whiskers for burn treatment, a spray film containing this composition, and a method for preparing the same. This invention uses tetra-needle-shaped zinc oxide whiskers and lavender essential oil as the main antibacterial components, supplemented with rhubarb and angelica dahurica to clear heat and purge fire, reduce inflammation and relieve pain, effectively controlling burns and post-burn infections caused by various factors. The invention also provides a method for preparing the spray film, which involves analyzing the effective components of rhubarb and angelica dahurica, extracting them with ethanol solvent, concentrating under reduced pressure, and then spray-drying to effectively control the content of effective components in the extract. Compared with existing formulations, this spray film is lower in cost, simpler to prepare, and incorporates tetra-needle-shaped zinc oxide whiskers with good antibacterial effects, making it suitable for treating burns caused by different reasons and for post-burn skin repair.

[0005] To achieve the above objectives, the present invention is implemented through the following technical solution:

[0006] A pharmaceutical composition for treating burns, which is composed of the following raw materials in mass parts: lavender essential oil 5-15 parts, 1-5 parts of tetraneedle-shaped zinc oxide whiskers, 5-20 parts of extracts of angelica and rhubarb, and 1 part of borneol.

[0007] Furthermore, the pharmaceutical composition for treating burns comprises the following raw materials in parts by weight: 8-10 parts lavender essential oil, 2-3 parts tetraneedle zinc oxide whiskers, 12-16 parts extracts of angelica and rhubarb, and 1 part borneol.

[0008] The lavender essential oil mentioned above can be obtained through commercial channels, such as lavender essential oil (Shandong Zhushi Pharmaceutical Group Co., Ltd., batch number: 21112206).

[0009] The tetrane-shaped zinc oxide whiskers are available commercially, such as tetrane-shaped zinc oxide crystals (Chengdu Tianyou Jingchuang Technology Co., Ltd., batch number: 22062301).

[0010] The preparation method of the extracts of Angelica dahurica and rhubarb includes the following steps: Rhubarb and Angelica dahurica are mixed at a mass ratio of 1:(1-2) and extracted with an ethanol aqueous solution. The extract and washing solution are collected and concentrated under reduced pressure. The powder is collected by spray drying to obtain the extracts of Angelica dahurica and rhubarb.

[0011] The extraction is a reflux extraction, and the extraction is performed at least once, specifically twice. Each extraction takes 1-2 hours, preferably 2 hours.

[0012] During the extraction, the amount of the ethanol-water solution used is 8-12 times the total mass of the rhubarb and angelica root.

[0013] The ethanol-water solution has an ethanol concentration of 40%-95%, preferably 40%-80%, and more preferably 60%.

[0014] The inlet temperature of the spray dryer is 100℃-140℃, preferably 110℃-130℃, and more preferably 120℃.

[0015] In this invention, the pharmaceutical composition for treating burns can be further formulated into a pharmaceutical preparation, the dosage form of which can be a spray film, a gel, or a spray.

[0016] In addition to the pharmaceutical composition for treating burns described in this invention, the pharmaceutical formulation may also include pharmaceutically acceptable excipients.

[0017] For spray film agents, excipients may include hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol-1788, etc.

[0018] Another object of the present invention is to provide a four-needle zinc oxide whisker spray film for the treatment of burns.

[0019] The four-needle zinc oxide whisker spray film for burn treatment provided by the present invention comprises the above-mentioned pharmaceutical composition, film-forming material and solvent; the pharmaceutical composition has a mass-volume percentage of 4%-8%, and the film-forming material has a mass-volume percentage of 2%-4%.

[0020] The solvents include ethanol and water.

[0021] The volume concentration of ethanol in the spray film agent is 50%-90%, preferably 80%.

[0022] The present invention also provides a method for preparing the above-mentioned four-needle zinc oxide whisker spray film for burn treatment.

[0023] The method for preparing the four-needle-shaped zinc oxide whisker spray film for burn treatment provided by the present invention includes the following steps:

[0024] A) Dissolve the film-forming material used to prepare the spray film agent in a suitable solvent to obtain a film material solution;

[0025] B) Dissolve the extracts of Bai Zhi and Dahuang in water to prepare a medicinal solution;

[0026] C) Pour the drug solution into the swollen membrane material solution and stir until homogeneous;

[0027] D) Dissolve the tetraneedle-shaped zinc oxide whiskers, lavender essential oil, and borneol in an appropriate amount of anhydrous ethanol, and add them to the solution in step C;

[0028] E) Add ethanol to make up the volume and stir until homogeneous to obtain the spray film agent.

[0029] In step A) of the above method, the film-forming material is hydroxypropyl methylcellulose, and the preparation method of its film material solution is as follows: hydroxypropyl methylcellulose is fully swollen with water to obtain the film material solution.

[0030] In step E) of the above method, after adding ethanol, the volume concentration of ethanol in the spray film agent is 50%-90%, preferably 80%.

[0031] Burns are an extremely complex traumatic injury. After a burn, the skin loses its normal protective barrier, resulting in exposed wounds, fluid leakage, severe pain, and a high risk of secondary infection. Therefore, early and proactive measures to control the burn condition, promote wound healing, and prevent subsequent secondary infections are crucial. This invention uses tetraneedle oxide whisker complex and lavender essential oil as antibacterial active ingredients, effective against various pathogens such as Staphylococcus aureus and Escherichia coli. The addition of rhubarb and angelica dahurica extracts provides heat-clearing, detoxifying, anti-inflammatory, and analgesic effects, effectively relieving infection and pain after burns. A spray film is prepared by mixing rhubarb, angelica dahurica extract, lavender essential oil, tetraneedle oxide whisker complex, and film-forming materials.

[0032] The present invention provides a four-needle-shaped zinc oxide whisker spray film agent and its preparation method, which has the following advantages:

[0033] 1. The formula is well-balanced and highly targeted, with antibacterial, heat-clearing and detoxifying, anti-inflammatory and analgesic effects, and can be used to treat symptoms caused by burns from various causes.

[0034] 2. Using tetraneedle oxide whisker composite as an antibacterial material for burn repair expands the application scenarios of tetraneedle oxide whisker composite.

[0035] 3. The formulation of this pharmaceutical composition is a spray film, which is easier to use and avoids discomfort caused by application compared to traditional ointments. Attached Figure Description

[0036] Figure 1 The prepared four-needle-shaped zinc oxide whisker spray film agent;

[0037] Figure 2 This is a model diagram of a burn.

[0038] Figure 3 This refers to the healing time of burned skin; Detailed Implementation

[0039] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited to the following embodiments. Unless otherwise specified, the methods described are conventional methods. Unless otherwise specified, the raw materials are all available from publicly available commercial sources.

[0040] The lavender essential oil used in the following examples was purchased from Shandong Zhushi Pharmaceutical Group Co., Ltd., production batch number: 21112206.

[0041] The four acicular zinc oxide whiskers are purchased from Chengdu Tianyou Jingchuang Technology Co., Ltd., and the production batch number is 22062301.

[0042] Example 1: A four-needle zinc oxide whisker spray film for burn treatment and its preparation method. The four-needle zinc oxide whisker spray film for burn treatment provided by the present invention includes a pharmaceutical composition, a film-forming material, and a solvent; the pharmaceutical composition has a mass-volume percentage of 4%, and the film-forming material (hydroxypropyl methylcellulose) has a mass-volume percentage of 3%; the solvent includes ethanol and water.

[0043] The volume concentration of ethanol in the spray film is 80%.

[0044] The above-mentioned pharmaceutical composition is composed of the following raw materials in parts by weight: 8 parts lavender essential oil, 2 parts tetraneedle-zinc oxide whisker complex, 12 parts extracts of angelica and rhubarb, and 1 part borneol.

[0045] The preparation method of the extract of Angelica dahurica and rhubarb includes the following steps: Rhubarb and Angelica dahurica are mixed at a mass ratio of 1:1 and extracted with ethanol solution. The extract and washing solution are collected and concentrated under reduced pressure. The powder is collected by spray drying to obtain the extract of Angelica dahurica and rhubarb.

[0046] The extraction is a reflux extraction, and the extraction is performed at least twice; each extraction takes 2 hours.

[0047] During the extraction, the amount of the ethanol-water solution used is 10 times the total mass of the rhubarb and angelica root.

[0048] The ethanol-water solution has an ethanol volume concentration of 60%.

[0049] The inlet temperature of the spray dryer is 120°C.

[0050] The preparation method of the spray film agent includes the following steps:

[0051] A) Take 6 parts of hydroxypropyl methylcellulose, add water and swell completely to prepare a membrane material solution;

[0052] B) Dissolve rhubarb and angelica powder in an appropriate amount of water to prepare a medicinal liquid;

[0053] C) Pour the drug solution into the swollen membrane material solution and stir until homogeneous;

[0054] D) Dissolve the four needle-shaped zinc oxide whiskers, essential oil, and borneol in an appropriate amount of anhydrous ethanol, and add it to the solution from step D;

[0055] E) Add ethanol to 20 mL, the final ethanol concentration is 80%, and stir well.

[0056] A photograph of the prepared tetra-needle-shaped zinc oxide whisker spray film is shown below. Figure 1 As shown.

[0057] Pharmacodynamic experiments:

[0058] Experimental methods:

[0059] According to the above preparation method, weigh the following components to prepare spray film agents 1-3 and blank spray film agents.

[0060]

[0061] Antibacterial test:

[0062] 1. Culture medium preparation

[0063] Weigh 2.01 g of sodium chloride, 1.00 g of yeast extract, 0.81 g of agar powder, and 2.01 g of proteose peptone, and dissolve them in an appropriate amount of water to prepare a medium. Solution. Use 5 mol·L -1 Adjust the pH to 7.4 with sodium hydroxide, add water to 200 mL, autoclave at 121°C for 15 min, and then cool to obtain the final product.

[0064] 2. Preparation of bacterial culture

[0065] Staphylococcus aureus and Escherichia coli were inoculated into petri dishes and incubated at 37°C for 24 hours. Single colonies were then picked and placed in sterile physiological saline, and the bacterial concentration was adjusted to 1.5 × 10⁻⁶ using a turbidimetric method. 8 cfu·mL -1 .

[0066] 3. Preparation of drug-containing filter paper discs

[0067] Cut the filter paper into 8mm pieces using a punch, autoclave at 121℃, then immerse the filter paper pieces in 200μL of drug solution (blank spray film agent, spray film agent 1, spray film agent 2, spray film agent 3) for 30min, remove and dry under reduced pressure at low temperature.

[0068] 4. Antibacterial zone test

[0069] Spread 100 μL of activated bacteria onto a petri dish, place drug-containing filter paper at the pre-marked position, incubate overnight in an incubator, and evaluate the antibacterial activity by measuring the diameter of the inhibition zone with calipers.

[0070] Pharmacodynamic experiments:

[0071] 1. Establishment of a burn model

[0072] The day before the experiment, mice were anesthetized with 10% chloral hydrate. The hair on the backs of the Kunming mice was trimmed with electric clippers, and the fine downy hairs were removed with sodium sulfide depilatory cream. Mice with damaged skin were discarded. A model was created using weights. A 20g weight was placed in boiling water for 2 minutes. One person gently pressed down on the mouse while another person placed the weight on the depilated area of ​​the mouse for 15 seconds, ensuring there was no gap between the weight and the skin. After 15 seconds, the weight was immediately removed, and the mice were dried with a hairdryer (cold air) and returned to their cages. The mice's condition was closely observed.

[0073] 2. Animal grouping and administration

[0074] Animals were randomly divided into a model group, a positive drug group, and a drug group. The model group was given 0.1 mL of blank spray film; the positive drug group was given 0.1 g of Jingwanhong ointment; and the drug groups were given 0.1 mL of spray film 1-3 respectively. The drugs were administered once in the morning and once in the evening. After administration, the drug solution was dried with a hair dryer. The administration was continued for seven days, and the wound healing time was recorded.

[0075] Burn model diagram as shown Figure 2 As shown.

[0076] result:

[0077] The healing time of the burned skin in each treatment group is as follows: Figure 3 As shown. By Figure 3 It can be seen that spray film 2 and 3 can significantly shorten the healing time of burned skin and promote skin repair.

[0078] The antibacterial test results for each treatment group are shown in Table 1. As can be seen from Table 1, the prepared spray film has good antibacterial effect, and Staphylococcus aureus and Escherichia coli are highly sensitive to it.

[0079] Table 1 shows the results of the antibacterial test.

[0080]

[0081] +++ indicates an inhibition zone diameter of 10-12mm, which is highly sensitive; ++ indicates an inhibition zone diameter of 8-10mm, which is moderately sensitive; - indicates no inhibition zone, which is insensitive.

Claims

1. A pharmaceutical composition for treating burns, comprising the following raw materials in parts by weight: 5-15 parts lavender essential oil, 1-5 parts tetraneedle zinc oxide whiskers, 5-20 parts extracts of angelica and rhubarb, and 1 part borneol.

2. The pharmaceutical composition according to claim 1, characterized in that: The pharmaceutical composition for treating burns comprises the following raw materials in parts by weight: 8-10 parts lavender essential oil, 2-3 parts tetraneedle zinc oxide whiskers, 12-16 parts extracts of angelica and rhubarb, and 1 part borneol.

3. The pharmaceutical composition according to claim 1 or 2, characterized in that: The preparation method of the extracts of Angelica dahurica and rhubarb includes the following steps: Rhubarb and Angelica dahurica are mixed at a mass ratio of 1:(1-2) and extracted with an ethanol aqueous solution. The extract and washing solution are collected and concentrated under reduced pressure. The powder is collected by spray drying to obtain the extracts of Angelica dahurica and rhubarb.

4. The pharmaceutical composition according to claim 3, characterized in that: The extraction is a reflux extraction, and the extraction is performed at least once, specifically twice; the extraction time for each extraction is 1-2 hours, preferably 2 hours. During the extraction, the amount of the ethanol aqueous solution used is 8-12 times the total mass of the rhubarb and angelica root herbs; The ethanol-water solution has an ethanol concentration of 40%-95%, preferably 40%-80%, and more preferably 60%. The inlet temperature of the spray dryer is 100℃-140℃, preferably 110℃-130℃, and more preferably 120℃.

5. A pharmaceutical preparation for the treatment of burns, comprising the pharmaceutical composition of any one of claims 1-4 and pharmaceutically acceptable excipients.

6. The pharmaceutical preparation according to claim 5, characterized in that: The dosage form of the pharmaceutical preparation is a spray film, gel, or aerosol.

7. A spray film for treating burns, comprising the pharmaceutical composition of any one of claims 1-4, a film-forming material, and a solvent; wherein the pharmaceutical composition comprises 4%-8% by mass and the film-forming material comprises 2%-4% by mass and the solvent comprises ethanol and water.

8. The spray film agent according to claim 7, characterized in that: The volume concentration of ethanol in the spray film agent is 50%-90%, preferably 80%; And / or, the film-forming material is selected from at least one of the following: hydroxypropyl methylcellulose, polyvinyl alcohol-1788.

9. A method for preparing the four-needle zinc oxide whisker spray film for burn treatment according to claim 7 or 8, comprising the following steps: A) Dissolve the film-forming material in a suitable solvent to prepare a film solution; B) Dissolve the extracts of Angelica dahurica and rhubarb in an appropriate amount of water to prepare a medicinal solution; C) Pour the drug solution into the swollen membrane material solution and stir until homogeneous; D) Dissolve the four needle-shaped zinc oxide whiskers, lavender essential oil, and borneol in an appropriate amount of anhydrous ethanol, and add them to the solution in step C; E) Add ethanol to make up the volume and stir until homogeneous to obtain the spray film agent.

10. The preparation method according to claim 9, characterized in that: In step A), the film-forming material is hydroxypropyl methylcellulose, and the preparation method of the film solution is as follows: hydroxypropyl methylcellulose is fully swollen with water to obtain the film solution. In step E), the addition of ethanol makes the volume concentration of ethanol in the spray film agent 50%-90%, preferably 80%.

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