Traditional Chinese medicine compound preparation for enhancing transdermal absorption and antibacterial activity as well as preparation and application of traditional Chinese medicine compound preparation

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a traditional Chinese medicine compound preparation for enhancing transdermal absorption and antibacterial activity as well as preparation and application thereof. According to the preparation, on the basis of classic components of patrinia, radix clematidis and ephedra, functional auxiliary materials are added to achieve performance improvement, and the preparation specifically comprises the following raw materials in parts by mass: 20 parts of patrinia, 15 parts of radix clematidis, 15 parts of ephedra, 0.1-0.5 part of a transdermal enhancer, 3-10 parts of a nano-liposome carrier and 0.2-0.8 part of a natural antibacterial synergist. The transdermal enhancer is prepared from menthol, laurocapram and D-limonene; the nano-liposome carrier comprises soybean lecithin, cholesterol and polyethylene glycol. Through the synergistic effect of the nano-liposome carrier, the composite transdermal enhancer and the natural antibacterial synergist, the nano-liposome can be flexibly matched with multiple dosage forms such as lotion, gel, cream and spray, the transdermal absorption of effective components is remarkably improved, the antibacterial spectrum is widened, and the inhibition effect on drug-resistant strains is enhanced.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a traditional Chinese medicine compound preparation that enhances transdermal absorption and antibacterial activity, as well as its preparation and application. Background Technology

[0002] Skin and mucous membrane-related diseases such as pruritus, eczema, various types of dermatitis, and gynecological inflammation are common and frequently occurring diseases in clinical practice. These diseases are often characterized by a long course, easy recurrence, and difficulty in complete cure. They are often accompanied by symptoms such as itching, redness, swelling, exudation, erosion, or local discomfort, which not only seriously affect patients' daily life, work, and sleep quality, but also place a significant burden on their physical and mental health. Traditional Chinese medicine external preparations, due to their advantages of direct action, high local concentration, good safety, and few systemic toxic side effects, hold a unique position and are widely used in the treatment of skin and mucous membrane diseases.

[0003] Currently, various topical Chinese medicine compositions have been disclosed in existing technologies. These compositions often improve local symptoms through their effects of clearing heat and detoxifying, dispelling wind and dampness, killing insects and relieving itching, and antibacterial and anti-inflammatory properties, providing some options and references for the clinical prevention and treatment of related diseases. For example, Chinese patent application CN100372550C discloses a Chinese medicine preparation and preparation method for treating pruritus and gynecological inflammation. This preparation uses *Patrinia scabiosaefolia* as the principal ingredient and *Clematis chinensis* and *Ephedra sinica* as adjuvant ingredients. It has the functions of clearing heat and detoxifying, dispelling wind and drying dampness, killing insects and relieving itching, gently expelling pathogens, and allowing the pathogens accumulated in the skin to be expelled from the skin. It has a wide range of indications and is used to treat gynecological vaginal inflammation, vulvar pruritus, measles, pruritus, eczema, pruritus caused by pesticide allergies, drug-induced skin allergies, rhinitis, scabies, frostbite, etc. It is an ideal topical Chinese medicine preparation for treating the above-mentioned diseases with significant efficacy, no obvious toxic side effects, and high safety and reliability. Although the preparation has certain therapeutic effects, the following problems exist in practical applications: (1) Low transdermal efficiency: The active ingredients in the traditional decoction extract (such as oleanolic acid, ephedrine, and anemone) have high molecular polarity and poor lipid solubility, making it difficult to penetrate the stratum corneum of the skin, resulting in insufficient local drug concentration and slow onset of action; (2) Insufficient stability: The water extract is prone to microbial growth, and preservatives (such as sodium benzoate) need to be added. Long-term use may cause skin irritation; (3) Limited antibacterial spectrum: Although it has inhibitory effects on Staphylococcus aureus and Candida albicans, it is not effective against drug-resistant strains (such as methicillin-resistant Staphylococcus aureus (MRSA) and fluconazole-resistant Candida); (4) Single dosage form: It only provides lotion, which cannot meet the needs of different indications (such as eczema exudation and frostbite cracking) for dosage forms (gel, cream, spray).

[0004] Chinese patent application CN114748556A discloses a gynecological external antibacterial effervescent tablet, which also uses Patrinia scabiosaefolia, Clematis chinensis, and Ephedra sinica as raw materials. The effervescent tablet form improves ease of use, but this patent focuses on dosage form improvement and does not address enhanced transdermal absorption or synergistic effects against drug-resistant bacteria. Chinese patent CN103278582B relates to a detection method for the aforementioned preparation, but does not involve improvements to the formulation or efficacy.

[0005] In summary, while existing topical preparations of three traditional Chinese medicines possess basic therapeutic effects, they suffer from significant drawbacks in practical applications, including low transdermal absorption efficiency, insufficient formulation stability, limited antibacterial spectrum, and limited dosage form compatibility. These limitations make it difficult to meet the demands for highly effective clinical treatment, safe use, and adaptability to various scenarios. Therefore, there is an urgent need to develop an upgraded version of these three-herb topical preparations that can significantly improve the transdermal absorption efficiency of the active ingredients, broaden the antibacterial spectrum and enhance the inhibitory effect on drug-resistant strains, improve formulation stability to reduce irritation, and expand dosage form compatibility. This would comprehensively enhance clinical therapeutic efficacy and application value. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity, as well as its preparation and application. This invention, while retaining the classic formula, introduces modern formulation technology to provide a three-herb compound preparation with high transdermal absorption efficiency, a broad antibacterial spectrum, good stability, and diverse dosage forms. *Patrinia scabiosaefolia* is the principal herb, clearing heat and detoxifying, eliminating carbuncles and draining pus; *Clematis chinensis* is the assistant herb, dispelling wind and dampness, unblocking meridians and relieving pain, assisting the principal herb in enhancing its ability to expel pathogens; *Ephedra sinica* is the adjuvant herb, gently dispersing pathogens and expelling accumulated toxins, while also promoting diuresis and reducing swelling. The three herbs work together to clear heat and detoxify, dispel wind and dry dampness, expel pathogens and relieve itching. Furthermore, this invention creatively incorporates a composite transdermal absorption enhancer and a nanoliposome carrier to guide the herbs directly to the affected area, enhancing transdermal absorption; the natural antibacterial synergist works synergistically with the principal, assistant, and adjuvant herbs to enhance the effects of resolving blood stasis and detoxifying, exhibiting unique advantages against drug-resistant strains. This invention achieves a dual enhancement of transdermal absorption and antibacterial activity through the synergistic effect of a nanoliposome carrier, a composite transdermal penetration enhancer, and a natural antibacterial synergist. Specifically, the nanoliposome carrier increases skin retention and penetration drive; the composite transdermal penetration enhancer improves the stratum corneum barrier, providing a channel for drug penetration; and the natural antibacterial synergist and the antibacterial components in the traditional Chinese medicine compound act on different antibacterial targets, producing a synergistic antibacterial effect, especially showing significant inhibitory activity against drug-resistant strains. This invention not only significantly improves the transdermal penetration efficiency of the active ingredient but also broadens the antibacterial spectrum and expands dosage form compatibility, overcoming the technical shortcomings of existing technologies such as low transdermal efficiency, poor inhibitory effect on drug-resistant strains, the need for chemical preservatives, and limited dosage form options.

[0007] The technical solution of this invention is: A compound preparation of three Chinese herbal medicines that enhances transdermal absorption and antibacterial activity includes the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.1-0.5 parts of transdermal absorption promoter, 3-10 parts of nanoliposome carrier, and 0.2-0.8 parts of natural antibacterial synergist.

[0008] Furthermore, the three-herb compound preparation for enhancing transdermal absorption and antibacterial activity includes the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal absorption promoter, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist.

[0009] In this invention, the source of *Patrinia scabiosaefolia* is the dried whole herb of *Patrinia scabiosaefolia*, a plant in the Valerianaceae family. The source of *Clematis manshurica* is the dried root and rhizome of *Clematis manshurica* Rupr., a plant in the Ranunculaceae family. The source of *Ephedra sinica* is the dried herbaceous stem of *Ephedra sinica* Stapf., *Ephedra intermedia* Schrenket C.A.Mey., or *Ephedra equisetina* Bge., all plants in the Ephedrine family.

[0010] Furthermore, the transdermal penetration enhancer includes menthol, laurocapram, and D-limonene.

[0011] Furthermore, the transdermal penetration enhancer is composed of menthol, laurocapram and D-limonene in a mass ratio of 12-15:3-5:1-2.

[0012] Furthermore, the transdermal penetration enhancer is composed of menthol, laurocapram, and D-limonene in a mass ratio of 13:4:1.

[0013] This invention employs menthol, laurocapram, and D-limonene in a specific ratio to form a composite transdermal penetration enhancer. Menthol and D-limonene can interfere with the lipid arrangement of the stratum corneum and increase lipid mobility; laurocapram can act on keratin in the stratum corneum, relax intercellular connections, and reduce drug penetration resistance. When the three are combined in a specific ratio, they form a multi-target, multi-layer transdermal penetration enhancement effect, significantly increasing the skin penetration of ingredients such as oleanolic acid, ephedrine, and anemonephrine, thus solving the problems of low transdermal efficiency and insufficient local concentration of traditional extracts.

[0014] Furthermore, the nanoliposome carrier comprises soybean lecithin, cholesterol, and polyethylene glycol.

[0015] Furthermore, the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 5-9:1-3:0.2-0.6.

[0016] Furthermore, the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.5.

[0017] Furthermore, the molecular weight of the polyethylene glycol is 400-600.

[0018] The nanoliposome carrier of this invention is composed of soybean lecithin, cholesterol, and polyethylene glycol of a specific molecular weight. Soybean lecithin and cholesterol form a lipid bilayer structure similar to the stratum corneum of the skin, exhibiting high biocompatibility and reducing skin irritation. Extensive inventive experiments have revealed that polyethylene glycol modification not only improves the spatial stability of nanoparticles, preventing drug aggregation, degradation, and oxidation, and significantly enhances the storage stability of extracts in formulations, but also synergizes with soybean lecithin, cholesterol, and a complex transdermal absorption enhancer to further improve the transdermal absorption rate of active ingredients. The nanoliposome carrier of this invention, composed of the above-mentioned components, can simultaneously encapsulate both lipophilic and hydrophilic active ingredients of traditional Chinese medicine, forming a homogeneous and stable system.

[0019] Furthermore, the natural antibacterial synergist is a combination of two or three of tea tree oil, eugenol, and thymol.

[0020] Furthermore, the natural antibacterial synergist is composed of tea tree oil, eugenol, and thymol in a mass ratio of 3:1:1.

[0021] This invention incorporates two or three of tea tree oil, eugenol, and thymol as natural antibacterial synergists. These components can disrupt bacterial cell membrane integrity and inhibit bacterial respiration and nucleic acid synthesis. When used in combination with antibacterial components of traditional Chinese medicine formulas, they can act on bacteria at multiple targets, significantly enhancing the inhibitory effect against common pathogens such as Staphylococcus aureus and Candida albicans. Simultaneously, by disrupting bacterial resistance mechanisms and reducing bacterial biofilm formation, it improves the inhibitory effect against drug-resistant strains such as MRSA and fluconazole-resistant Candida, thus broadening the antibacterial spectrum. This invention maintains formulation stability without the need for chemical preservatives such as sodium benzoate, improving safety in use.

[0022] In this invention, the nanoliposome carrier increases skin retention and penetration; the composite transdermal penetration enhancer improves the stratum corneum barrier, providing a channel for drug penetration; and the traditional Chinese medicine compound and natural antibacterial synergist achieve complementary antibacterial spectrum and synergistic antibacterial intensity. The synergistic effect of these three components ultimately achieves a comprehensive effect of high transdermal permeability, high stability, strong antibacterial activity, high safety, and resistance to drug resistance, effectively solving the technical problems of poor transdermal permeability, instability, and narrow antibacterial spectrum in traditional topical Chinese medicine preparations.

[0023] Furthermore, the cumulative transdermal transdermal dose of ephedrine in the formulation is ≥50 μg / cm² over 24 hours, and the MIC value against methicillin-resistant Staphylococcus aureus is ≤16 μg / mL.

[0024] Furthermore, the dosage form of the traditional Chinese medicine compound preparation includes lotion, gel, cream or spray.

[0025] This invention also provides a method for preparing the traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity, comprising the following steps: S1. Crush Patrinia scabiosifolia, sieve to obtain Patrinia scabiosifolia powder. Add water to the Patrinia scabiosifolia powder, the amount of water being 7-10 times the mass of the Patrinia scabiosifolia powder. Add a compound enzyme, perform enzymatic hydrolysis, inactivate the enzyme, add an ethanol aqueous solution, reflux for extraction, centrifuge to obtain supernatant and filter residue. Add an ethanol aqueous solution to the filter residue, reflux for extraction, centrifuge to obtain filtrate. Combine the supernatant and filtrate to obtain Patrinia scabiosifolia extract. S2. Crush Clematis chinensis, sieve to obtain Clematis chinensis powder, add ethanol aqueous solution to Clematis chinensis powder, the amount of ethanol aqueous solution added is 6-9 times the mass of Clematis chinensis powder, reflux for extraction, centrifuge to obtain supernatant and filter residue, add ethanol aqueous solution to filter residue, reflux for extraction, centrifuge to obtain filtrate; combine supernatant and filtrate to obtain Clematis chinensis extract; S3. Crush ephedra, sieve it to obtain ephedra powder, add water to the ephedra powder and decoct it. The amount of water added is 10-15 times the mass of the ephedra powder. Filter it to obtain filtrate and residue. Add ethanol aqueous solution to the residue, reflux to extract, filter it to obtain filtrate. Combine the two filtrates to obtain ephedra extract. S4 Combine the Patrinia scabiosifolia extract obtained in step S1, the Clematis chinensis extract obtained in step S2, and the Ephedra extract obtained in step S3, concentrate them, and obtain an extract. S5. Add solvent to nanoliposome carrier, add extract obtained in step S4, add buffer, homogenize, and obtain drug-loaded liposomes. S6. The drug-loaded liposomes obtained in step S5 are mixed with transdermal absorption enhancers and natural antibacterial synergists to prepare a traditional Chinese medicine compound preparation that enhances transdermal absorption and antibacterial activity.

[0026] In step S1, the complex enzyme is composed of pectinase and β-glucosidase in a mass ratio of 4-7:1. The amount of complex enzyme added is 2-5% of the mass of Patrinia scabiosifolia powder. The enzymatic hydrolysis temperature is 35-45℃ and the enzymatic hydrolysis time is 2-4 hours. The volume fraction of the ethanol aqueous solution is 75-85%, the reflux extraction temperature is 60-70℃, and the time is 1-1.5 hours.

[0027] In step S2, the volume fraction of the ethanol-water solution is 65-75%, the reflux extraction temperature is 70-80℃, and the extraction time is 1-2 hours; in step S3, the decoction time is 40-60 minutes, the volume fraction of the ethanol-water solution is 55-65%, the reflux extraction temperature is 75-85℃, and the extraction time is 50-80 minutes.

[0028] The solvent in step S5 is anhydrous ethanol, and the homogenization conditions are 800 bar high-pressure homogenization three times; the preparation in step S6 is sterilized by a 0.22 μm filter membrane.

[0029] This invention employs a compound enzymatic hydrolysis-assisted ethanol reflux extraction method to obtain Patrinia scabiosaefolia extract. Enzymatic hydrolysis disrupts the plant cell wall structure, allowing for a more complete release of intracellular active ingredients and enhancing efficacy. This invention also utilizes a stepwise extraction method—first water decoction followed by ethanol reflux—to obtain Ephedra extract, achieving full retention of both water-soluble and fat-soluble active ingredients. Furthermore, this invention extracts Patrinia scabiosaefolia, Clematis chinensis, and Ephedra separately, then combines the extracts to maximize the retention of antibacterial, anti-inflammatory, and transdermal penetration-promoting active ingredients in the compound formula, thereby improving its therapeutic effect.

[0030] Furthermore, in step S1, the sieve mesh size is 60-100 mesh.

[0031] Further, the complex enzyme described in step S1 is composed of pectinase and β-glucosidase in a mass ratio of 4-7:1.

[0032] Further, the complex enzyme described in step S1 is composed of pectinase and β-glucosidase in a mass ratio of 5:1.

[0033] Furthermore, the amount of the compound enzyme added in step S1 is 2-5% of the mass of the Patrinia scabiosifolia powder.

[0034] Furthermore, in step S1, the enzymatic hydrolysis temperature is 35-45℃, and the enzymatic hydrolysis time is 2-4 hours.

[0035] Furthermore, the volume fraction of the ethanol-water solution in step S1 is 75-85%.

[0036] Furthermore, the amount of ethanol-water solution added in step S1 is 9-12 times the mass of the Patrinia scabiosifolia powder.

[0037] Furthermore, in step S1, the reflux extraction temperature is 60-70℃, and the reflux extraction time is 1-1.5 hours.

[0038] Furthermore, in step S2, the sieve mesh size is 60-100 mesh.

[0039] Furthermore, the volume fraction of the ethanol-water solution in step S2 is 65-75%.

[0040] Furthermore, in step S2, the reflux extraction temperature is 70-80℃, and the reflux extraction time is 1-2 hours.

[0041] Furthermore, in step S3, the sieve mesh size is 60-100 mesh.

[0042] Furthermore, in step S3, the simmering time with water is 40-60 minutes.

[0043] Furthermore, the volume fraction of the ethanol-water solution in step S3 is 55-65%.

[0044] Furthermore, the amount of ethanol-water solution added in step S3 is 7-9 times the mass of ephedra powder.

[0045] Furthermore, in step S3, the reflux extraction temperature is 75-85℃, and the reflux extraction time is 50-80 minutes.

[0046] Further, step S4 concentrates the product to a relative density of 1.10 (60°C).

[0047] Furthermore, the solvent in step S5 is anhydrous ethanol.

[0048] Another object of the present invention is to provide the application of the above-mentioned three-herb compound preparation with enhanced transdermal absorption and antibacterial activity in the preparation of medicaments for treating skin itching, eczema, dermatitis or gynecological inflammation.

[0049] Compared with the prior art, the present invention has the following advantages: (1) Significantly enhanced transdermal absorption. This invention significantly improves the transdermal efficiency of active ingredients through the synergistic effect of nanoliposomes and transdermal enhancers. In vitro Franz diffusion cell experiments have verified that this invention significantly increases the cumulative transdermal amount of ephedrine and other components over 24 hours. The transdermal amount of ephedrine over 24 hours reaches 52.7 μg / cm², with a synergistic effect ratio of 2.83. This promotes the rapid penetration of drugs into the deep lesions and solves the problem of low transdermal efficiency of traditional preparations.

[0050] (2) Significantly enhanced antibacterial activity. Through the synergistic effect of traditional Chinese medicine compound and natural antibacterial synergist, the present invention achieves a MIC value of 16 μg / mL against MRSA and a synergistic antibacterial FICI index of 0.375, which significantly broadens the antibacterial spectrum and reduces the MIC value against MRSA and fluconazole-resistant Candida albicans, thus solving the problem of poor efficacy of traditional preparations against drug-resistant strains.

[0051] (3) Significantly enhanced formulation stability. This invention utilizes the synergistic effect of PEG-modified nanoliposomes and natural antibacterial synergists. The total number of microorganisms in the formulation is <10 CFU / mL after 6 months at 40℃ / 75%RH, eliminating the need for chemical preservatives and resulting in higher safety.

[0052] (4) Enhanced dosage form adaptability. This invention achieves dosage form diversification. The same core prescription can be flexibly adapted to dosage forms such as lotion, gel, cream, and spray to meet the needs of different lesions and has wider clinical applicability.

[0053] (5) High safety and enhanced clinical efficacy. Animal skin irritation test (rabbit) showed no erythema or edema, and the sensitization rate was 0%. Clinical trials have verified that the clinical efficacy of this product in treating eczema is as high as 97.5%, and it is non-irritating to the skin. Detailed Implementation

[0054] The present invention will be further described below through specific embodiments, but this is not a limitation of the present invention. Those skilled in the art can make various modifications or improvements based on the basic idea of ​​the present invention, but as long as they do not depart from the basic idea of ​​the present invention, they are all within the scope of the present invention.

[0055] Unless otherwise specified, all raw materials used in this invention are commercially available. For example, tea tree oil (CAS: 68647-73-4) is available from Shanghai Aladdin Biochemical Technology Co., Ltd.; pectinase (CAS: 9032-75-1) is available from Shanghai Aladdin Biochemical Technology Co., Ltd.; β-glucosidase (CAS: 9001-22-3) is available from Beijing Solarbio Technology Co., Ltd.; and cellulase (CAS: 9012-54-8) is available from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0056] Example 1: A traditional Chinese medicine compound preparation (lotion) that enhances transdermal absorption and antibacterial activity. The traditional Chinese medicine compound preparation for enhancing transdermal absorption and antibacterial activity comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.1 parts of transdermal absorption promoter, 3 parts of nanoliposome carrier, and 0.2 parts of natural antibacterial synergist; the transdermal absorption promoter is composed of menthol, laurocapram, and D-limonene in a mass ratio of 12:5:2; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 5:3:0.6; the molecular weight of polyethylene glycol is 400; and the natural antibacterial synergist is composed of tea tree oil and eugenol in a mass ratio of 3:1.

[0057] The preparation method of the traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity includes the following steps: S1. Patrinia scabiosifolia is pulverized and passed through a 60-mesh sieve to obtain Patrinia scabiosifolia powder. Water is added to the powder at a ratio of 7 times its mass. A compound enzyme, composed of pectinase and β-glucosidase at a mass ratio of 4:1, is added at a ratio of 2% to 35°C for 2 hours. The enzyme is then inactivated at 85°C for 10 minutes. A 75% ethanol aqueous solution (9 times its mass) is added, and the mixture is refluxed at 60°C for 1.5 hours. After centrifugation, a supernatant and a filter residue are obtained. A 75% ethanol aqueous solution (9 times its mass) is added to the filter residue, and the mixture is refluxed at 60°C for 1.5 hours. After centrifugation, a filtrate is obtained. The supernatant and filtrate are combined to obtain the Patrinia scabiosifolia extract. S2. Crush Clematis chinensis and pass it through a 60-mesh sieve to obtain Clematis chinensis powder. Add a 65% (v / v) ethanol aqueous solution to the Clematis chinensis powder, with the amount of ethanol aqueous solution being 6 times the mass of the Clematis chinensis powder. Reflux extraction is performed at 70℃ for 2 hours. After centrifugation, the supernatant and filter residue are obtained. Add a 65% (v / v) ethanol aqueous solution to the filter residue, with the amount of ethanol aqueous solution being 6 times the mass of the Clematis chinensis powder. Reflux extraction is performed at 70℃ for 2 hours. After centrifugation, the filtrate is obtained. Combine the supernatant and filtrate to obtain the Clematis chinensis extract. S3. Crush ephedra and pass it through a 60-mesh sieve to obtain ephedra powder. Add water to the ephedra powder and decoct it. The amount of water added is 10 times the mass of the ephedra powder. The decoction time is 40 minutes. Filter to obtain filtrate and residue. Add 55% ethanol aqueous solution to the residue. The amount of ethanol aqueous solution added is 7 times the mass of the ephedra powder. Reflux extraction is performed at 75℃ for 50 minutes. Filter to obtain filtrate. Combine the two filtrates to obtain ephedra extract. S4 Combine the Patrinia scabiosifolia extract obtained in step S1, the Clematis chinensis extract obtained in step S2, and the Ephedra sinica extract obtained in step S3, concentrate them, and concentrate them to a relative density of 1.10 (60℃) to obtain an extract. In step S5, anhydrous ethanol is added to the nanoliposome carrier at a volume ratio of 2 mL / g. The extract obtained in step S4 is added, and phosphate buffer (pH 6.0) at 50°C is injected at a volume ratio of 20 mL / g to the extract obtained in step S4. The mixture is then sheared at 10,000 rpm for 5 minutes and homogenized under high pressure (800 bar × 3) to obtain drug-loaded liposomes. S6. The transdermal absorption enhancer and natural antibacterial synergist are pre-dissolved in a small amount of anhydrous ethanol (1 mL of ethanol per gram of transdermal absorption enhancer), added to the drug-loaded liposomes obtained in step S5, mixed, stirred evenly, and kept warm and stirred in a 40°C water bath for 30 minutes to ensure that the lipid-soluble components are fully loaded into the liposome bilayer. Purified water is added, with a volume-to-mass ratio of purified water to the extract obtained in step S4 of 176 mL / g. The mixture is sterilized by a 0.22 μm filter membrane, filled, and prepared as a traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity.

[0058] Example 2: A traditional Chinese medicine compound preparation (lotion) that enhances transdermal absorption and antibacterial activity. The traditional Chinese medicine compound preparation for enhancing transdermal absorption and antibacterial activity comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.1-0.5 parts of transdermal absorption promoter, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist; the transdermal absorption promoter is composed of menthol, laurocapram, and D-limonene in a mass ratio of 15:3:1; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 9:1:0.2; the molecular weight of polyethylene glycol is 600; and the natural antibacterial synergist is composed of tea tree oil and thymol in a mass ratio of 2:1.

[0059] The preparation method of the traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity includes the following steps: S1. Patrinia scabiosifolia is pulverized and passed through a 100-mesh sieve to obtain Patrinia scabiosifolia powder. Water is added to the powder in an amount 10 times its mass. A compound enzyme, composed of pectinase and β-glucosidase in a 7:1 mass ratio, is added in an amount 5% of the powder's mass. Enzymatic hydrolysis is performed at 45℃ for 4 hours, followed by enzyme inactivation at 85℃ for 10 minutes. An 85% ethanol aqueous solution, in an amount 12 times its mass, is added. The mixture is then refluxed at 70℃ for 1 hour. After centrifugation, a supernatant and a filter residue are obtained. An 85% ethanol aqueous solution, in an amount 12 times its mass, is added to the filter residue. The mixture is then refluxed at 70℃ for 1 hour. After centrifugation, a filtrate is obtained. The supernatant and filtrate are combined to obtain the Patrinia scabiosifolia extract. S2. Crush Clematis chinensis and pass it through a 100-mesh sieve to obtain Clematis chinensis powder. Add a 75% (v / v) ethanol aqueous solution to the Clematis chinensis powder, with the amount of ethanol aqueous solution being 9 times the mass of the Clematis chinensis powder. Reflux extraction is performed at 80℃ for 1 hour. After centrifugation, the supernatant and filter residue are obtained. Add a 75% (v / v) ethanol aqueous solution to the filter residue, with the amount of ethanol aqueous solution being 9 times the mass of the Clematis chinensis powder. Reflux extraction is performed at 80℃ for 1 hour. After centrifugation, the filtrate is obtained. Combine the supernatant and filtrate to obtain the Clematis chinensis extract. S3. Crush ephedra and pass it through a 100-mesh sieve to obtain ephedra powder. Add water to the ephedra powder and decoct it. The amount of water added is 15 times the mass of the ephedra powder. The decoction time is 60 minutes. Filter to obtain filtrate and residue. Add 65% ethanol aqueous solution to the residue. The amount of ethanol aqueous solution added is 9 times the mass of the ephedra powder. Reflux extraction is performed at 85℃ for 50 minutes. Filter to obtain filtrate. Combine the two filtrates to obtain ephedra extract. S4 Combine the Patrinia scabiosifolia extract obtained in step S1, the Clematis chinensis extract obtained in step S2, and the Ephedra sinica extract obtained in step S3, concentrate them, and concentrate them to a relative density of 1.10 (60℃) to obtain an extract. In step S5, anhydrous ethanol is added to the nanoliposome carrier at a volume ratio of 2 mL / g. The extract obtained in step S4 is added, and phosphate buffer (pH 6.0) at 50°C is injected at a volume ratio of 20 mL / g to the extract obtained in step S4. The mixture is then sheared at 15,000 rpm for 10 minutes and homogenized under high pressure (800 bar × 3) to obtain drug-loaded liposomes. S6. The transdermal absorption enhancer and natural antibacterial synergist are pre-dissolved in a small amount of anhydrous ethanol (1 mL of ethanol per gram of transdermal absorption enhancer), added to the drug-loaded liposomes obtained in step S5, mixed, stirred evenly, and kept warm and stirred in a 40°C water bath for 30 minutes to ensure that the lipid-soluble components are fully loaded into the liposome bilayer. Purified water is added, with a volume-to-mass ratio of purified water to the extract obtained in step S4 of 176 mL / g. The mixture is sterilized by a 0.22 μm filter membrane, filled, and prepared as a traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity.

[0060] Example 3: A traditional Chinese medicine compound preparation (lotion) that enhances transdermal absorption and antibacterial activity. The traditional Chinese medicine compound preparation for enhancing transdermal absorption and antibacterial activity comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal absorption promoter, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist; the transdermal absorption promoter is composed of menthol, laurocapram, and D-limonene in a mass ratio of 13:4:1; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.5; the molecular weight of polyethylene glycol is 400; and the natural antibacterial synergist is composed of tea tree oil, eugenol, and thymol in a mass ratio of 3:1:1.

[0061] The preparation method of the traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity includes the following steps: S1. Patrinia scabiosifolia is pulverized and passed through an 80-mesh sieve to obtain Patrinia scabiosifolia powder. Water is added to the powder in an amount 9 times its mass. A compound enzyme, composed of pectinase and β-glucosidase in a mass ratio of 5:1, is added in an amount 3% of the powder's mass. Enzymatic hydrolysis is performed at 40℃ for 3 hours, followed by enzyme inactivation at 85℃ for 10 minutes. An 80% ethanol aqueous solution, in an amount 10 times its mass, is added. The mixture is then refluxed at 65℃ for 1 hour. After centrifugation, a supernatant and a filter residue are obtained. An 80% ethanol aqueous solution, in an amount 10 times its mass, is added to the filter residue. The mixture is then refluxed at 65℃ for 1 hour. After centrifugation, a filtrate is obtained. The supernatant and filtrate are combined to obtain the Patrinia scabiosifolia extract. S2. Crush Clematis chinensis and pass it through an 80-mesh sieve to obtain Clematis chinensis powder. Add a 70% (v / v) ethanol aqueous solution to the Clematis chinensis powder, with the amount of ethanol aqueous solution being 8 times the mass of the Clematis chinensis powder. Reflux extraction is performed at 75℃ for 1.5 hours. After centrifugation, the supernatant and filter residue are obtained. Add a 70% (v / v) ethanol aqueous solution to the filter residue, with the amount of ethanol aqueous solution being 8 times the mass of the Clematis chinensis powder. Reflux extraction is performed at 75℃ for 1.5 hours. After centrifugation, the filtrate is obtained. Combine the supernatant and filtrate to obtain the Clematis chinensis extract. S3. Crush ephedra and pass it through an 80-mesh sieve to obtain ephedra powder. Add water to the ephedra powder and decoct it. The amount of water added is 12 times the mass of the ephedra powder. The decoction time is 50 minutes. Filter to obtain filtrate and residue. Add a 60% ethanol aqueous solution to the residue. The amount of ethanol aqueous solution added is 8 times the mass of the ephedra powder. Reflux extraction is performed at 80℃ for 60 minutes. Filter to obtain filtrate. Combine the two filtrates to obtain ephedra extract. S4 Combine the Patrinia scabiosifolia extract obtained in step S1, the Clematis chinensis extract obtained in step S2, and the Ephedra sinica extract obtained in step S3, concentrate them, and concentrate them to a relative density of 1.10 (60℃) to obtain an extract. In step S5, anhydrous ethanol is added to the nanoliposome carrier at a volume ratio of 2 mL / g. The extract obtained in step S4 is added, and phosphate buffer (pH 6.0) at 50°C is injected at a volume ratio of 20 mL / g to the extract obtained in step S4. The mixture is then sheared at 12,000 rpm for 7 minutes and homogenized under high pressure (800 bar × 3) to obtain drug-loaded liposomes. S6. The transdermal absorption enhancer and natural antibacterial synergist are pre-dissolved in a small amount of anhydrous ethanol (1 mL of ethanol per gram of transdermal absorption enhancer), added to the drug-loaded liposomes obtained in step S5, mixed, stirred evenly, and kept warm and stirred in a 40°C water bath for 30 minutes to ensure that the lipid-soluble components are fully loaded into the liposome bilayer. Purified water is added, with a volume-to-mass ratio of purified water to the extract obtained in step S4 of 176 mL / g. The mixture is sterilized by a 0.22 μm filter membrane, filled, and prepared as a traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity.

[0062] Example 4: A traditional Chinese medicine compound preparation (external gel) that enhances transdermal absorption and antibacterial activity. The traditional Chinese medicine compound preparation for enhancing transdermal absorption and antibacterial activity comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal absorption promoter, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist; the transdermal absorption promoter is composed of menthol, laurocapram, and D-limonene in a mass ratio of 13:4:1; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.5; the molecular weight of polyethylene glycol is 400; and the natural antibacterial synergist is composed of tea tree oil, eugenol, and thymol in a mass ratio of 3:1:1.

[0063] The preparation method of the traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity includes the following steps: S1. Patrinia scabiosifolia is pulverized and passed through an 80-mesh sieve to obtain Patrinia scabiosifolia powder. Water is added to the powder in an amount 9 times its mass. A compound enzyme, composed of pectinase and β-glucosidase in a mass ratio of 5:1, is added in an amount 3% of the powder's mass. Enzymatic hydrolysis is performed at 40℃ for 3 hours, followed by enzyme inactivation at 85℃ for 10 minutes. An 80% ethanol aqueous solution, in an amount 10 times its mass, is added. The mixture is then refluxed at 65℃ for 1 hour. After centrifugation, a supernatant and a filter residue are obtained. An 80% ethanol aqueous solution, in an amount 10 times its mass, is added to the filter residue. The mixture is then refluxed at 65℃ for 1 hour. After centrifugation, a filtrate is obtained. The supernatant and filtrate are combined to obtain the Patrinia scabiosifolia extract. S2. Crush Clematis chinensis and pass it through an 80-mesh sieve to obtain Clematis chinensis powder. Add a 70% (v / v) ethanol aqueous solution to the Clematis chinensis powder, with the amount of ethanol aqueous solution being 8 times the mass of the Clematis chinensis powder. Reflux extraction is performed at 75℃ for 1.5 hours. After centrifugation, the supernatant and filter residue are obtained. Add a 70% (v / v) ethanol aqueous solution to the filter residue, with the amount of ethanol aqueous solution being 8 times the mass of the Clematis chinensis powder. Reflux extraction is performed at 75℃ for 1.5 hours. After centrifugation, the filtrate is obtained. Combine the supernatant and filtrate to obtain the Clematis chinensis extract. S3. Crush ephedra and pass it through an 80-mesh sieve to obtain ephedra powder. Add water to the ephedra powder and decoct it. The amount of water added is 12 times the mass of the ephedra powder. The decoction time is 50 minutes. Filter to obtain filtrate and residue. Add a 60% ethanol aqueous solution to the residue. The amount of ethanol aqueous solution added is 8 times the mass of the ephedra powder. Reflux extraction is performed at 80℃ for 60 minutes. Filter to obtain filtrate. Combine the two filtrates to obtain ephedra extract. S4 Combine the Patrinia scabiosifolia extract obtained in step S1, the Clematis chinensis extract obtained in step S2, and the Ephedra sinica extract obtained in step S3, concentrate them, and concentrate them to a relative density of 1.10 (60℃) to obtain an extract. In step S5, anhydrous ethanol is added to the nanoliposome carrier at a volume ratio of 2 mL / g. The extract obtained in step S4 is added, and 50°C phosphate buffer (pH 6.0) is injected at a volume ratio of 20 mL / g to the extract obtained in step S4. After high-speed shearing, the mixture is homogenized under high pressure (800 bar × 3) to obtain drug-loaded liposomes. S6. The transdermal penetration enhancer and the natural antibacterial synergist are pre-dissolved in a small amount of anhydrous ethanol (1 mL of ethanol is added for every gram of transdermal penetration enhancer), added to the drug-loaded liposomes obtained in step S5, mixed, stirred evenly, and kept warm and stirred in a 40°C water bath for 30 minutes to fully load the lipid-soluble components into the liposome bilayer, thus obtaining the mixture. S7 Disperse Carbomer 940 in purified water and allow it to swell by standing. The mass-to-volume ratio of Carbomer 940 to purified water is 8:200 g / mL, and a swollen solution is obtained. S8. Add the mixture obtained in step S6 to the swelling solution obtained in step S7, add triethanolamine dropwise to adjust the pH to 6.5, stir until a transparent gel is formed, dispense into containers, and the product is obtained.

[0064] Example 5: A traditional Chinese medicine compound preparation (cream) that enhances transdermal absorption and antibacterial activity. The traditional Chinese medicine compound preparation for enhancing transdermal absorption and antibacterial activity comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal absorption promoter, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist; the transdermal absorption promoter is composed of menthol, laurocapram, and D-limonene in a mass ratio of 13:4:1; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.5; the molecular weight of polyethylene glycol is 400; and the natural antibacterial synergist is composed of tea tree oil, eugenol, and thymol in a mass ratio of 3:1:1.

[0065] The preparation method of the traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity is similar to that in Example 3.

[0066] The difference from Example 3 is that in step S6, the transdermal penetration enhancer and the natural antibacterial synergist are pre-dissolved in a small amount of anhydrous ethanol (1 mL of ethanol per gram of transdermal penetration enhancer), added to the drug-loaded liposomes obtained in step S5, mixed, stirred evenly, and kept warm and stirred in a 40°C water bath for 30 minutes to fully load the lipid-soluble components into the liposome bilayer. Then, an O / W type emulsifying matrix (8 parts of glyceryl stearate, 5 parts of cetyl alcohol, and 8 parts of glycerol) is added and emulsified for 60 minutes to obtain the final product.

[0067] Example 6: A traditional Chinese medicine compound preparation (spray) that enhances transdermal absorption and antibacterial activity. The traditional Chinese medicine compound preparation for enhancing transdermal absorption and antibacterial activity comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal absorption promoter, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist; the transdermal absorption promoter is composed of menthol, laurocapram, and D-limonene in a mass ratio of 13:4:1; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.5; the molecular weight of polyethylene glycol is 400; and the natural antibacterial synergist is composed of tea tree oil, eugenol, and thymol in a mass ratio of 3:1:1.

[0068] The preparation method of the traditional Chinese medicine compound preparation with enhanced transdermal absorption and antibacterial activity is similar to that in Example 3.

[0069] The difference from Example 3 is that in step S6, the transdermal penetration enhancer and the natural antibacterial synergist are pre-dissolved in a small amount of anhydrous ethanol (1 mL of ethanol per gram of transdermal penetration enhancer), added to the drug-loaded liposomes obtained in step S5, mixed, stirred evenly, and kept warm and stirred in a 40°C water bath for 30 minutes to ensure that the lipid-soluble components are fully loaded into the liposome bilayer. Purified water is added, with a volume-to-mass ratio of purified water to the extract obtained in step S4 of 176 mL / g. The mixture is then sterilized using a 0.22 μm filter membrane and filled into an aerosol can.

[0070] Comparative Example 1: A traditional Chinese medicine compound preparation (lotion) The traditional Chinese medicine compound preparation comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal penetration enhancer, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist; the transdermal penetration enhancer is composed of menthol and laurocapram in a mass ratio of 14:4; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.5; the molecular weight of polyethylene glycol is 400; the natural antibacterial synergist is composed of tea tree oil, eugenol, and thymol in a mass ratio of 3:1:1.

[0071] The preparation method of the traditional Chinese medicine compound preparation is similar to that in Example 3.

[0072] The difference from Example 3 is that the transdermal penetration enhancer is composed of menthol and laurocapram in a mass ratio of 14:4.

[0073] Comparative Example 2: A traditional Chinese medicine compound preparation (lotion) The traditional Chinese medicine compound preparation comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal penetration enhancer, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist; the transdermal penetration enhancer is composed of menthol, laurocapram, and D-limonene in a mass ratio of 13:4:1; the nanoliposome carrier is composed of soybean lecithin and cholesterol in a mass ratio of 8:2.5; and the natural antibacterial synergist is composed of tea tree oil, eugenol, and thymol in a mass ratio of 3:1:1.

[0074] The preparation method of the traditional Chinese medicine compound preparation is similar to that in Example 3.

[0075] The difference from Example 3 is that the nanoliposome carrier is composed of soybean lecithin and cholesterol in a mass ratio of 8:2.5.

[0076] Comparative Example 3: A traditional Chinese medicine compound preparation (lotion) The traditional Chinese medicine compound preparation comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal penetration enhancer, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist; the transdermal penetration enhancer is composed of menthol, laurocapram, and D-limonene in a mass ratio of 13:4:1; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.5; the molecular weight of polyethylene glycol is 400; the natural antibacterial synergist is composed of tea tree oil, eugenol, and cinnamaldehyde in a mass ratio of 3:1:1.

[0077] The preparation method of the traditional Chinese medicine compound preparation is similar to that in Example 3.

[0078] The difference from Example 3 is that the natural antibacterial synergist is composed of tea tree oil, eugenol and cinnamaldehyde in a mass ratio of 3:1:1.

[0079] Comparative Example 4: A traditional Chinese medicine compound preparation (lotion) The traditional Chinese medicine compound preparation comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal penetration enhancer, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist; the transdermal penetration enhancer is composed of menthol, laurocapram, and D-limonene in a mass ratio of 13:4:1; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.5; the molecular weight of polyethylene glycol is 400; the natural antibacterial synergist is composed of tea tree oil, eugenol, and thymol in a mass ratio of 3:1:1.

[0080] The preparation method of the traditional Chinese medicine compound preparation is similar to that in Example 3.

[0081] The difference from Example 3 is that in step S1 of the preparation method of the traditional Chinese medicine compound preparation, the compound enzyme is composed of pectinase and cellulase in a mass ratio of 5:1.

[0082] Comparative Example 5 (prepared by method CN1724012A) Prepared according to the method of CN1724012A: Take 200g of Patrinia scabiosaefolia, 150g of Clematis chinensis and 150g of Ephedra sinica, add 10 times the amount of water and decoct 3 times (1 hour for the first time, 45 minutes each for the second and third times), combine the decoctions, concentrate under reduced pressure to a relative density of 1.02-1.04 (45℃), let stand overnight, filter, add 5g of sodium benzoate, add water to 1000mL, and the lotion is obtained.

[0083] Control A: Preparations containing only traditional Chinese medicine extracts The preparation containing only Chinese herbal extracts includes the following raw materials and their mass fractions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, and 15 parts of Ephedra sinica.

[0084] The preparation method of the preparation containing only Chinese herbal extracts is similar to that of Example 3. The difference between the preparation method and Example 3 is that after obtaining the extract in step S4, purified water is directly added. The volume-to-mass ratio of purified water to the extract obtained in step S4 is 176 mL / g. The product is sterilized by a 0.22 μm filter membrane, filled, and prepared.

[0085] Control B: Formulations containing only traditional Chinese medicine extracts and transdermal penetration enhancers The preparation containing only Chinese herbal extracts and transdermal penetration enhancers includes the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, and 0.3 parts of transdermal penetration enhancer; the transdermal penetration enhancer is composed of menthol, laurocapram, and D-limonene in a mass ratio of 13:4:1.

[0086] The preparation method of the formulation containing only Chinese herbal extract and transdermal penetration enhancer is similar to that of Example 3. The difference between the preparation method and Example 3 is that in step S5, the transdermal penetration enhancer is pre-dissolved in a small amount of anhydrous ethanol (1 mL of ethanol is added per gram of transdermal penetration enhancer), added to the extract obtained in step S4, mixed, stirred evenly, kept warm and stirred in a 40°C water bath for 30 minutes, purified water is added, the volume-to-mass ratio of purified water to the extract obtained in step S4 is 176 mL / g, sterilized by a 0.22 μm filter membrane, and then filled.

[0087] Control C: Formulations containing only traditional Chinese medicine extracts and nanoliposomes The preparation containing only Chinese herbal extracts and nanoliposomes comprises the following raw materials and their mass proportions: 20 parts of Patrinia scabiosaefolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, and 10 parts of nanoliposome carrier; the nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.5; the molecular weight of the polyethylene glycol is 400.

[0088] The preparation method of the formulation containing only Chinese herbal extracts and nanoliposomes is similar to that of Example 3. The difference between the preparation method and Example 3 is that in step S6, the drug-loaded liposomes obtained in step S5 are kept warm and stirred in a water bath at 40°C for 30 minutes to fully load the lipid-soluble components into the liposome bilayer. Purified water is added, and the volume-to-mass ratio of purified water to the extract obtained in step S4 is 176 mL / g. The mixture is then sterilized using a 0.22 μm filter membrane and filled into containers.

[0089] Experimental Example 1: In vitro Franz diffusion cell transdermal test 1. Experimental Materials Example 3: A traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity prepared; and the traditional Chinese medicine compound preparations (lotions) prepared in Comparative Examples 1, 2, and 5.

[0090] 2. Experimental Methods Using the Franz diffusion cell method, isolated mouse skin was used as the permeability barrier. Samples were taken at 0, 2, 4, 6, 8, 12, and 24 hours to determine the ephedrine content in the receiving fluid and calculate the cumulative transdermal dose over 24 hours. To verify the synergistic effect, control groups were added: a formulation containing only the herbal extract (Control A), a formulation containing only the herbal extract and a transdermal penetration enhancer (Control B), and a formulation containing only the herbal extract and nanoliposomes (Control C).

[0091] 3. Experimental Results The experimental results are shown in Table 1.

[0092] Table 1 Comparison of experimental results in the in vitro Franz diffusion cell.

[0093] As can be seen from the results of the in vitro Franz diffusion cell transdermal test in Table 1, the transdermal transdermal ephedrine transdermal amount (52.7 μg / cm²) of the traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity prepared in Example 3 of this invention is 2.83 times that of the basic preparation (18.6 μg / cm²) in Comparative Example 5, which is significantly higher than that of Comparative Example 1, Comparative Example 2, Comparative Example 5 and each control group, proving that the compound transdermal activator and nanoliposomes have a significant synergistic effect on transdermal efficacy.

[0094] Test Example 2: Antibacterial Activity Test 1. Experimental Materials Example 3: A traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity prepared; Comparative Examples 3 and 5: Traditional Chinese medicine compound preparations (lotions).

[0095] 2. Experimental Methods The minimum inhibitory concentrations (MICs) against methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300) and fluconazole-resistant Candida albicans (ATCC 10231) were determined using the micro-broth dilution method. The partial inhibitory concentration index (FICI) of the combination of traditional Chinese medicine extracts and natural antibacterial synergists was determined using the checkerboard method; a FICI ≤ 0.5 indicated a synergistic effect.

[0096] 3. Experimental Results The experimental results are shown in Table 2.

[0097] Table 2 Comparison of antibacterial activity test results

[0098] As can be seen from the comparison of antibacterial activity tests in Table 2, the traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity prepared in Example 3 of this invention has significantly lower MIC values ​​against MRSA and drug-resistant Candida albicans than the basic preparation (100 μg / mL) in Comparative Example 5, and the FICI index is 0.375 (≤0.5). This indicates that the traditional Chinese medicine compound and the natural antibacterial synergist have a significant synergistic antibacterial effect, and this invention significantly broadens the antibacterial spectrum.

[0099] Experiment Example 3: Stability Test 1. Experimental Materials Example 3: A traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity prepared; and the traditional Chinese medicine compound preparations (lotions) prepared in Comparative Examples 2, 3, and 5.

[0100] 2. Experimental Methods The samples were placed at 40℃ and 75% RH for 6 months, and the total number of aerobic bacteria, molds and yeasts was determined according to the method in General Chapter 1105 of Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0101] 3. Experimental Results The experimental results are shown in Table 3.

[0102] Table 3 Comparison of stability test results

[0103] As can be seen from the stability test results in Table 3, the total number of microorganisms in the traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity prepared in Example 3 of the present invention after being placed at 40℃ / 75% RH for 6 months is significantly lower than that in Comparative Examples 2, 3 and 5. This indicates that the present invention has excellent stability.

[0104] Test Example 4: Animal Skin Irritation Test 1. Experimental Materials Example 3: A traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity.

[0105] 2. Experimental Methods According to the "Cosmetic Safety Technical Specifications" (2015 edition), 20 healthy rabbits were selected for skin irritation tests. Samples were applied to intact and broken skin on the back once a day for 14 consecutive days. Erythema and edema reactions were observed and recorded according to the "Skin Irritation Reaction Scoring Standard", and the Primary Irritation Index (PII) was calculated.

[0106] 3. Experimental Results: The primary irritation index of Group 3 in Example 3 was 0, and the sensitization rate was 0%. Histopathological examination showed no pathological changes such as hyperkeratosis or inflammatory cell infiltration at the application site. This indicates that the formulation of the present invention has high safety and no skin irritation.

[0107] Case Study 5: Clinical Trial 1. Experimental Materials Example 3: A traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity prepared; Comparative Examples 1 and 4: Traditional Chinese medicine compound preparations (lotions).

[0108] 2. Experimental Methods 120 patients meeting the diagnostic criteria for eczema in the "Standards for Diagnosis and Efficacy Evaluation of Diseases in Traditional Chinese Medicine" were selected and randomly divided into three groups: Example 3, Comparative Example 1, and Comparative Example 4, with 40 patients in each group. A randomized, double-blind, parallel-controlled design was used. Medication was administered twice daily for 7 consecutive days. The efficacy evaluation criteria were based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines": Cured: Complete disappearance of skin lesions and pruritus, efficacy index ≥ 95%; Significantly effective: Most skin lesions disappeared, and pruritus was significantly reduced, 70% ≤ efficacy index < 95%; Effective: Partial disappearance of skin lesions and some reduction in pruritus, 30% ≤ efficacy index < 70%; Ineffective: Insignificant disappearance of skin lesions, no reduction or worsening of pruritus, efficacy index < 30%. Clinical effective rate = (Cure + Significantly effective + Effective) / Total number of cases × 100%.

[0109] 3. Experimental Results The experimental results are shown in Table 4.

[0110] Table 4 Comparison of Clinical Trial Results

[0111] As can be seen from the comparison of clinical trial results in Table 4, the clinical efficacy rate of the traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity prepared using Example 3 of the present invention is as high as 97.5%, including 24 cured cases, 10 cases with significant improvement, 5 cases with improvement, and 1 case without effect. In contrast, the clinical efficacy rate of the traditional Chinese medicine compound preparation (lotion) prepared using Comparative Example 1 is 87.5%, including 15 cured cases, 13 cases with significant improvement, 7 cases with improvement, and 5 cases without effect. The clinical efficacy rate of the traditional Chinese medicine compound preparation (lotion) prepared using Comparative Example 4 is only 80.0%, including 14 cured cases, 10 cases with significant improvement, 8 cases with improvement, and 8 cases without effect. Therefore, the clinical efficacy of the traditional Chinese medicine compound preparation (lotion) with enhanced transdermal absorption and antibacterial activity prepared using Example 3 of the present invention is significantly better than that of Comparative Example 1 and Comparative Example 4.

[0112] Experimental Example 6: Dosage Form Suitability Study Sensory evaluation and stability studies were conducted on four dosage forms: Example 3 (lotion), Example 4 (gel), Example 5 (cream), and Example 6 (spray). The results are shown in Table 5.

[0113] Table 5 Results of the study on different dosage forms

[0114] The results in Table 5 show that the core prescription of this invention can be flexibly adapted to various dosage forms to meet the needs of different lesions, and has a wider applicability than existing single dosage forms.

[0115] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A three-herb compound preparation that enhances transdermal absorption and antibacterial activity, characterized in that, It includes the following raw materials and their weight proportions: 20 parts of Patrinia scabiosifolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.1-0.5 parts of transdermal penetration enhancer, 3-10 parts of nanoliposome carrier, and 0.2-0.8 parts of natural antibacterial synergist.

2. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 1, characterized in that, The ingredients and their weight proportions are as follows: 20 parts of Patrinia scabiosifolia, 15 parts of Clematis chinensis, 15 parts of Ephedra sinica, 0.3 parts of transdermal penetration enhancer, 10 parts of nanoliposome carrier, and 0.8 parts of natural antibacterial synergist.

3. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 1 or 2, characterized in that, The transdermal penetration enhancers include menthol, laurocapram, and D-limonene.

4. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 3, characterized in that, The transdermal penetration enhancer is composed of menthol, laurocapram and D-limonene in a mass ratio of 12-15:3-5:1-2.

5. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 4, characterized in that, The transdermal penetration enhancer is composed of menthol, laurocapram and D-limonene in a mass ratio of 13:4:

1.

6. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 1 or 2, characterized in that, The nanoliposome carrier comprises soybean lecithin, cholesterol, and polyethylene glycol.

7. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 6, characterized in that, The nanoliposome carrier is composed of soybean lecithin, cholesterol and polyethylene glycol in a mass ratio of 5-9:1-3:0.2-0.

6.

8. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 7, characterized in that, The nanoliposome carrier is composed of soybean lecithin, cholesterol, and polyethylene glycol in a mass ratio of 8:2:0.

5.

9. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 6, characterized in that, The molecular weight of the polyethylene glycol is 400-600.

10. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 1 or 2, characterized in that, The natural antibacterial synergist is a combination of two or three of tea tree oil, eugenol, and thymol.

11. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 10, characterized in that, The natural antibacterial synergist is composed of tea tree oil, eugenol, and thymol in a mass ratio of 3:1:

1.

12. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to claim 1, characterized in that, The formulation contains ephedrine with a cumulative transdermal transdermal dose of ≥50 μg / cm² over 24 hours and a MIC value of ≤16 μg / mL against methicillin-resistant Staphylococcus aureus.

13. The three-herb compound preparation for enhancing transdermal absorption and antibacterial activity according to any one of claims 1-12, characterized in that, The dosage forms of the traditional Chinese medicine compound preparations include lotions, gels, creams, or sprays.

14. The method for preparing a three-herb compound preparation with enhanced transdermal absorption and antibacterial activity according to any one of claims 1-13, characterized in that, Includes the following steps: S1. Crush Patrinia scabiosifolia, sieve to obtain Patrinia scabiosifolia powder. Add water to the Patrinia scabiosifolia powder, the amount of water being 7-10 times the mass of the Patrinia scabiosifolia powder. Add a compound enzyme, perform enzymatic hydrolysis, inactivate the enzyme, add an ethanol aqueous solution, reflux for extraction, centrifuge to obtain supernatant and filter residue. Add an ethanol aqueous solution to the filter residue, reflux for extraction, centrifuge to obtain filtrate. Combine the supernatant and filtrate to obtain Patrinia scabiosifolia extract. S2. Crush Clematis chinensis, sieve to obtain Clematis chinensis powder, add ethanol aqueous solution to Clematis chinensis powder, the amount of ethanol aqueous solution added is 6-9 times the mass of Clematis chinensis powder, reflux for extraction, centrifuge to obtain supernatant and filter residue, add ethanol aqueous solution to filter residue, reflux for extraction, centrifuge to obtain filtrate; combine supernatant and filtrate to obtain Clematis chinensis extract; S3. Crush ephedra, sieve it to obtain ephedra powder, add water to the ephedra powder and decoct it. The amount of water added is 10-15 times the mass of the ephedra powder. Filter it to obtain filtrate and residue. Add ethanol aqueous solution to the residue, reflux to extract, filter it to obtain filtrate. Combine the two filtrates to obtain ephedra extract. S4 Combine the Patrinia scabiosifolia extract obtained in step S1, the Clematis chinensis extract obtained in step S2, and the Ephedra extract obtained in step S3, concentrate them, and obtain an extract. S5. Add solvent to nanoliposome carrier, add extract obtained in step S4, add buffer, homogenize, and obtain drug-loaded liposomes. S6. The drug-loaded liposomes obtained in step S5 are mixed with transdermal absorption enhancers and natural antibacterial synergists to prepare a traditional Chinese medicine compound preparation that enhances transdermal absorption and antibacterial activity.

15. The preparation method according to claim 14, characterized in that, The complex enzyme mentioned in step S1 is composed of pectinase and β-glucosidase in a mass ratio of 4-7:

1. The amount of complex enzyme added is 2-5% of the mass of Patrinia scabiosifolia powder. The enzymatic hydrolysis temperature is 35-45℃ and the enzymatic hydrolysis time is 2-4 hours. The volume fraction of the ethanol aqueous solution is 75-85%, the reflux extraction temperature is 60-70℃, and the time is 1-1.5 hours.

16. The preparation method according to claim 14, characterized in that, In step S2, the volume fraction of the ethanol-water solution is 65-75%, the reflux extraction temperature is 70-80℃, and the extraction time is 1-2 hours; in step S3, the decoction time is 40-60 minutes, the volume fraction of the ethanol-water solution is 55-65%, the reflux extraction temperature is 75-85℃, and the extraction time is 50-80 minutes.

17. The preparation method according to claim 14, characterized in that, The solvent in step S5 is anhydrous ethanol, and the homogenization conditions are 800 bar high-pressure homogenization three times; the preparation in step S6 is sterilized by a 0.22 μm filter membrane.

18. The use of the three-herb compound preparation with enhanced transdermal absorption and antibacterial activity according to any one of claims 1-13 in the preparation of a medicament for treating pruritus, eczema, dermatitis or gynecological inflammation.

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