An antibacterial and anti-inflammatory external preparation and a preparation method thereof

Abstract

The present application relates to the field of external preparation, and in particular to an antibacterial and anti-inflammatory external preparation and a preparation method thereof, which comprises, by weight fraction, 5-10 parts of oil phase of traditional Chinese medicine extract, 10-15 parts of water phase of traditional Chinese medicine extract, 3-5 parts of oleic acid polyethylene glycol glyceride, 2-5 parts of medium-chain triglyceride, 15-20 parts of gel base, and 5-8 parts of functional regulation. The external preparation takes Cortex Toxicodendri as the monarch for clearing heat and detoxifying, takes Cortex Phellodendri and Groundsel as the ministers for clearing heat and drying dampness and broad-spectrum antibacterial, takes Fructus Kochiae for attacking itching, takes Glycyrrhiza for regulating acute and chronic, and takes Borneol for leading the drug to penetrate. The external preparation directly has the effects of antibacterial, anti-inflammatory, analgesic, antipruritic, and promoting repair.

Description

Technical Field

[0001] This invention relates to the field of topical preparations, and more specifically, to an antibacterial and anti-inflammatory topical preparation and its preparation method. Background Technology

[0002] Bacterial infections, inflammation, and related pain of the skin and mucous membranes are common clinical conditions, such as vulvitis, urethritis, folliculitis, minor burns, trauma, and postoperative wound infections. These conditions not only cause patients severe discomfort such as redness, swelling, heat, pain, and itching, but if not treated properly, they may also lead to more serious systemic infections or chronic conditions.

[0003] Currently, topical medications used clinically to treat such localized inflammatory infections mainly include chemical antibiotic ointments (such as mupirocin ointment and fusidic acid cream), sulfonamide preparations (such as silver sulfadiazine cream), and nonsteroidal anti-inflammatory drug gels. While Western medicine preparations have a faster onset of action, long-term use can easily lead to bacterial resistance, and some drugs pose risks such as skin irritation, allergies, or systemic absorption side effects. Furthermore, traditional ointments or creams generally have drawbacks such as being greasy, having poor breathability, easily staining clothing, and being inconvenient to clean, affecting patient compliance.

[0004] Traditional Chinese medicine (TCM) has many heat-clearing, detoxifying, dampness-drying, and itch-relieving herbs (such as Phellodendron bark, Sophora flavescens, honeysuckle, and dandelion) that have broad-spectrum antibacterial, anti-inflammatory, and analgesic effects in treating sores, carbuncles, and damp-heat accumulation. Formulating these herbs into topical preparations offers potential advantages such as multi-target action, low risk of drug resistance, and relatively fewer side effects. Currently, some topical TCM washes, ointments, or gels are available on the market, such as compound Phellodendron bark liquid and anti-inflammatory and itch-relieving washes, which meet clinical needs to some extent. However, existing topical TCM preparations still have several significant drawbacks, such as: Traditional Chinese medicine (TCM) compound formulas contain complex components, many of which are pharmacologically active alkaloids, flavonoids, glycosides, etc., with large molecular weights or high lipid solubility. These components are difficult to effectively penetrate the stratum corneum or mucosal barrier to reach the deep lesions, resulting in "medicinal efficacy not reaching the disease site" and significantly reduced therapeutic effects. Although some preparations have attempted to add traditional penetration enhancers such as azone, the penetration-enhancing effect is limited and lacks specificity.

[0005] On the other hand, the short residence time of the medication at the affected area makes it impossible to achieve a long-lasting effect. Currently, the mainstream topical dosage forms of traditional Chinese medicine are mostly liquid washes, ordinary hydrogels, or ointments. Liquid dosage forms are highly fluid and are easily washed away by bodily fluids (such as sweat and urine) or wiped away by clothing after application, requiring frequent administration (4-6 times a day), which is inconvenient for patients and causes large fluctuations in blood drug concentration. Although ordinary ointments or gels have a certain degree of adhesiveness, their ability to resist physical rinsing is still relatively weak, and their retention is particularly unsatisfactory in frequently active or moist areas (such as the vulva and groin), making it difficult to maintain an effective local drug concentration. Summary of the Invention

[0006] The purpose of this invention is to provide an antibacterial and anti-inflammatory topical preparation, with *Gnaphalium affine* as the principal ingredient for clearing heat and detoxifying, *Phellodendron chinense* and *Senecio scandens* as secondary ingredients for clearing heat, drying dampness, and broad-spectrum antibacterial effects, *Kochia scoparia* for relieving itching, licorice for harmonizing and relieving spasms, and borneol for guiding the medicine to its full effect. This topical preparation directly possesses antibacterial, anti-inflammatory, analgesic, antipruritic, and repair-promoting effects.

[0007] Another objective of this invention is to provide a method for preparing an antibacterial and anti-inflammatory topical preparation. Through gentle heat treatment following supercritical CO2 extraction, and alcohol precipitation and resin refining in the water extraction process, potential hazardous substances such as pyrrolizidine alkaloids (PAs) and macromolecular impurities such as starch, gums, and tannins in *Senecio scandens* are removed. This reduces the product's toxicity and mucosal irritation.

[0008] The technical problem solved by this invention is achieved by the following technical solution.

[0009] On one hand, embodiments of the present invention provide an antibacterial and anti-inflammatory topical preparation, which, by weight, comprises 5-10 parts of the oil phase of a traditional Chinese medicine extract, 10-15 parts of the aqueous phase of a traditional Chinese medicine extract, 3-5 parts of polyethylene glycol oleate, 2-5 parts of medium-chain triglycerides, 15-20 parts of a gel matrix, and 5-8 parts of a functional regulator.

[0010] By weight, the oil phase of the herbal extract includes the following raw materials: 20-30 parts of *Gentiana scabra*, 5-15 parts of *Phellodendron chinense*, and 5-15 parts of *Senecio scandens*. By weight, the aqueous phase of the herbal extract comprises the following raw materials: 10-20 parts of Kochia scoparia, 5-10 parts of Chrysanthemum morifolium, and 3-10 parts of Glycyrrhiza uralensis.

[0011] In some embodiments of the present invention, the oil phase of the herbal extract includes the following raw materials: 20 parts of *Gnaphalium affine*, 8 parts of *Phellodendron chinense*, and 5 parts of *Senecio scandens*. By weight, the aqueous phase of the herbal extract comprises the following raw materials: 10 parts of Kochia scoparia, 5 parts of Chrysanthemum morifolium, and 3 parts of Glycyrrhiza uralensis. In some embodiments of the present invention, the oil phase of the herbal extract includes the following raw materials: 30 parts of *Gnaphalium affine*, 15 parts of *Phellodendron chinense*, and 15 parts of *Senecio scandens*. By weight, the aqueous phase of the herbal extract comprises the following raw materials: 20 parts of Kochia scoparia, 10 parts of Chrysanthemum morifolium, and 10 parts of Glycyrrhiza uralensis. In some embodiments of the present invention, the functional modifier comprises, by weight, 0.3-0.5 parts of borneol, 0.2-0.5 parts of menthol, 1-3 parts of azone, 1.5-2 parts of panthenol, and 2-3 parts of glycerin. In some embodiments of the present invention, the gel matrix comprises the following raw materials in parts by weight: 15-20 parts of poloxamer and 0.5-1.5 parts of chitosan.

[0012] On the other hand, this invention provides a method for preparing an antibacterial and anti-inflammatory topical preparation, comprising the following steps: S1, preparing the oil phase and aqueous phase of the traditional Chinese medicine extract; S2, mix the oil phase of the Chinese herbal extract, polyethylene glycol oleate, medium-chain triglycerides, and functional regulators, and stir in a water bath at 50-60℃ until completely clear to obtain the nano oil phase; S3, In an ice-water bath, poloxamer is added to water and magnetically stirred until homogeneous to obtain poloxamer solution; chitosan is dissolved in water containing acetic acid, and then the aqueous phase of the traditional Chinese medicine extract is added and mixed until homogeneous to obtain a mixed solution; The mixture was added to the poloxamer solution under ice-water bath and stirring, and stirred until homogeneous to obtain the aqueous gel phase. S4. Under high-speed shearing, the nano oil phase is added to the gel aqueous phase, followed by high-speed shearing for 5-10 minutes and vacuum degassing to obtain the topical preparation.

[0013] In some embodiments of the present invention, the method for preparing the oil phase of the traditional Chinese medicine extract includes the following steps: The medicinal materials were pulverized into coarse powder and placed in an extraction vessel for supercritical CO2 extraction for 2-3 hours. The extract was then separated in two stages to obtain the crude oil phase. Add anhydrous sodium sulfate to the crude oil phase, stir to dehydrate, and filter; Add glycerol, stir and reflux at 85-90℃ for 30-40 minutes, centrifuge, and take the supernatant oil layer to obtain the oil phase of the Chinese herbal extract.

[0014] In some embodiments of the present invention, the conditions for supercritical CO2 extraction are: pressure: 25-35 MPa, temperature: 45-55 °C, CO2 flow rate: 20-30 L / h.

[0015] In some embodiments of the present invention, the method for preparing the aqueous phase of the traditional Chinese medicine extract includes the following steps: Place all medicinal materials into an extraction tank, add 8-10 times the volume of water, and soak for 30-4 minutes; heat to boiling, maintain a gentle boil, and reflux for 1-1.5 hours; filter and collect the first decoction; add 8 volumes of water to the residue, reflux for 1-1.5 hours, filter, and collect the second decoction; combine the decoctions, transfer to a vacuum concentration tank, and concentrate to 1 / 5 of the original volume to obtain a concentrated solution; While stirring, add 95% ethanol to the concentrate to achieve an alcohol content of 60%-65%. Continue stirring for 20-30 minutes, let stand at 4°C for 24 hours, collect the supernatant, recover the ethanol from the supernatant until the supernatant has no alcohol odor, then refine it using macroporous adsorption resin, and vacuum concentrate it into a thick paste to obtain the aqueous phase of the traditional Chinese medicine extract.

[0016] In some embodiments of the present invention, the relative density of the aqueous phase of the traditional Chinese medicine extract is 1.25-1.35 at 60°C.

[0017] Compared with the prior art, the embodiments of the present invention have at least the following advantages or beneficial effects: The external preparation provided by this invention uses *Gnaphalium affine* as the principal ingredient to clear heat and detoxify, *Phellodendron chinense* and *Senecio scandens* as secondary ingredients to clear heat, dry dampness, and have broad-spectrum antibacterial effects, *Kochia scoparia* to specifically relieve itching, licorice to harmonize and soothe, and borneol to guide the medicine to its full effect. This external preparation directly possesses antibacterial, anti-inflammatory, analgesic, antipruritic, and repair-promoting effects.

[0018] This dual delivery system, combining nanoemulsion drug delivery with a thermosensitive gel, enhances the solubility and penetration efficiency of lipid-soluble drugs. The thermosensitive gel allows the drug to be sprayed as a liquid and then gelled upon contact with the skin, forming a physical protective film. Nanoemulsion droplets enhance stratum corneum penetration, forming an intradermal reservoir, while the thermosensitive gel film resists scouring and friction. Chitosan provides bioadhesion to mucous membranes. This prolongs the effective residence time of the drug at the affected area, reducing the frequency of daily application.

[0019] The preparation method provided by this invention removes potentially hazardous substances such as pyrrolizidine alkaloids (PAs) and macromolecular impurities such as starch, gums, and tannins from Senecio scandens through gentle heat treatment following supercritical CO2 extraction, and alcohol precipitation and resin refining in the water extraction process. This reduces the toxic side effects and mucosal irritation of the product. Detailed Implementation

[0020] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.

[0021] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other. The present invention will now be described in detail with reference to specific embodiments.

[0022] This invention provides an antibacterial and anti-inflammatory topical preparation, which, by weight, comprises 5-10 parts of the oil phase of a traditional Chinese medicine extract, 10-15 parts of the aqueous phase of a traditional Chinese medicine extract, 3-5 parts of polyethylene glycol oleate, 2-5 parts of medium-chain triglycerides, 15-20 parts of a gel matrix, and 5-8 parts of a functional regulator.

[0023] By weight, the oil phase of the herbal extract comprises the following raw materials: 20-30 parts of *Gnaphalium affine*, 5-15 parts of *Phellodendron chinense*, and 5-15 parts of *Senecio scandens*; the aqueous phase of the herbal extract comprises the following raw materials: 10-20 parts of *Kochia scoparia*, 5-10 parts of *Chrysanthemum indicum*, and 3-10 parts of *Glycyrrhiza uralensis*.

[0024] Preferably, the oil phase of the herbal extract comprises the following raw materials: 20 parts of *Gnaphalium affine*, 8 parts of *Phellodendron chinense*, and 5 parts of *Senecio scandens*; the aqueous phase of the herbal extract comprises the following raw materials: 10 parts of *Kochia scoparia*, 5 parts of *Chrysanthemum indicum*, and 3 parts of licorice. The oil phase of the herbal extract includes the following raw materials: 30 parts of *Gentiana scabra*, 15 parts of *Phellodendron chinense*, and 15 parts of *Senecio scandens*; the aqueous phase of the herbal extract includes the following raw materials: 20 parts of *Kochia scoparia*, 10 parts of *Chrysanthemum indicum*, and 10 parts of licorice. The functional modifiers include: 0.3-0.5 parts borneol, 0.2-0.5 parts menthol, 1-3 parts azone, 1.5-2 parts panthenol, and 2-3 parts glycerin. The gel matrix comprises the following raw materials: 15-20 parts of poloxamer and 0.5-1.5 parts of chitosan.

[0025] The preparation method of the above-mentioned topical preparation includes the following steps: S1, preparing the oil phase and aqueous phase of the traditional Chinese medicine extract; S2, mix the oil phase of the Chinese herbal extract, polyethylene glycol oleate, medium-chain triglycerides, and functional regulators, and stir in a water bath at 50-60℃ until completely clear to obtain the nano oil phase; S3, In an ice-water bath, poloxamer is added to water and magnetically stirred until homogeneous to obtain poloxamer solution; chitosan is dissolved in water containing acetic acid, and then the aqueous phase of the traditional Chinese medicine extract is added and mixed until homogeneous to obtain a mixed solution; The mixture was added to the poloxamer solution under ice-water bath and stirring, and stirred until homogeneous to obtain the aqueous gel phase. S4. Under high-speed shearing, the nano oil phase is added to the gel aqueous phase, followed by high-speed shearing for 5-10 minutes and vacuum degassing to obtain the topical preparation.

[0026] Specifically, the preparation method of the oil phase of the traditional Chinese medicine extract includes the following steps: The medicinal materials were pulverized into coarse powder and placed in an extraction vessel for supercritical CO2 extraction for 2-3 hours. The extract was then separated in two stages to obtain the crude oil phase. Add anhydrous sodium sulfate to the crude oil phase, stir to dehydrate, and filter; Add glycerol, stir and reflux at 85-90℃ for 30-40 min, centrifuge, and collect the supernatant oil layer to obtain the oil phase of the herbal extract. The conditions for supercritical CO2 extraction are: pressure: 25-35 MPa, temperature: 45-55℃; CO2 flow rate: 20-30 L / h.

[0027] Specifically, the preparation method of the aqueous phase of the traditional Chinese medicine extract includes the following steps: Place all medicinal materials into an extraction tank, add 8-10 times the volume of water, and soak for 30-4 minutes; heat to boiling, maintain a gentle boil, and reflux for 1-1.5 hours; filter and collect the first decoction; add 8 volumes of water to the residue, reflux for 1-1.5 hours, filter, and collect the second decoction; combine the decoctions, transfer to a vacuum concentration tank, and concentrate to 1 / 5 of the original volume to obtain a concentrated solution; While stirring, add 95% ethanol to the concentrate to achieve an alcohol content of 60%-65%. Continue stirring for 20-30 minutes, let stand at 4°C for 24 hours, collect the supernatant, recover the ethanol from the supernatant until the supernatant has no alcohol odor, then refine using macroporous adsorption resin, and vacuum concentrate to a thick paste to obtain the aqueous phase of the traditional Chinese medicine extract. At 60°C, the relative density of the aqueous phase of the traditional Chinese medicine extract is 1.25-1.35.

[0028] The features and performance of the present invention will be further described in detail below with reference to embodiments. Example 1 Prepare the ingredients according to the following proportions: Oil phase of Chinese herbal extracts: 20 parts of *Gentiana scabra*, 8 parts of *Phellodendron chinense*, and 5 parts of *Senecio scandens*. Aqueous phase of Chinese herbal extract: 10 parts of Kochia scoparia, 5 parts of Chrysanthemum morifolium, and 3 parts of Glycyrrhiza uralensis.

[0029] Functional modifiers: 0.5 parts borneol, 0.5 parts menthol, 3 parts azone, 2 parts panthenol, 3 parts glycerin; Gel matrix: 20 parts poloxamer, 1.5 parts chitosan.

[0030] The oil phase of the traditional Chinese medicine extract is prepared as follows: Each medicinal material is pulverized into coarse powder and placed in an extraction vessel for supercritical CO2 extraction for 2-3 hours; the extract is separated in two stages to obtain the crude oil phase; anhydrous sodium sulfate is added to the crude oil phase, stirred to dehydrate, and filtered; glycerol is then added, and the mixture is stirred and refluxed at 85-90℃ for 30-40 minutes, centrifuged, and the supernatant oil layer is collected to obtain the oil phase of the traditional Chinese medicine extract. The supercritical CO2 extraction conditions are: pressure: 25-35 MPa, temperature: 45-55℃; CO2 flow rate: 20-30 L / h. Prepare the aqueous phase of the Chinese herbal extract as follows: Place each herb into an extraction tank, add 8-10 times its volume of water, and soak for 30-4 minutes; heat to boiling, maintain a gentle boil, and reflux for 1-1.5 hours; filter and collect the first decoction; add 8 volumes of water to the residue, reflux for 1-1.5 hours, filter, and collect the second decoction; combine the decoctions, transfer to a vacuum concentration tank, and concentrate to 1 / 5 of the original volume to obtain the concentrated solution; While stirring, add 95% ethanol to the concentrate to achieve an alcohol content of 60%-65%. Continue stirring for 20-30 minutes, let stand at 4°C for 24 hours, collect the supernatant, recover the ethanol from the supernatant until the supernatant has no alcohol odor, then refine using macroporous adsorption resin, and vacuum concentrate to a thick paste to obtain the aqueous phase of the herbal extract. At 60°C, the relative density of the aqueous phase of the herbal extract is 1.25-1.35.

[0031] Prepare the topical preparation according to the following combination and steps: Eight parts of the oil phase of the Chinese herbal extract, 12 parts of the aqueous phase of the Chinese herbal extract, 4 parts of polyethylene glycol oleate, 3 parts of medium-chain triglycerides, 18 parts of gel matrix, and 6 parts of functional regulator.

[0032] S2, mix the oil phase of the Chinese herbal extract, polyethylene glycol oleate, medium-chain triglycerides, and functional regulators, and stir in a water bath at 50-60℃ until completely clear to obtain the nano oil phase; S3, In an ice-water bath, poloxamer is added to water and magnetically stirred until homogeneous to obtain poloxamer solution; chitosan is dissolved in water containing acetic acid, and then the aqueous phase of the traditional Chinese medicine extract is added and mixed until homogeneous to obtain a mixed solution; The mixture was added to the poloxamer solution under ice-water bath and stirring, and stirred until homogeneous to obtain the aqueous gel phase. S4. Under high-speed shearing, the nano oil phase is added to the gel aqueous phase, followed by high-speed shearing for 5-10 minutes and vacuum degassing to obtain the topical preparation.

[0033] Example 2 Prepare the ingredients according to the following proportions: Oil phase of Chinese herbal extracts: 20 parts of *Gentiana scabra*, 8 parts of *Phellodendron chinense*, and 5 parts of *Senecio scandens*. Aqueous phase of Chinese herbal extract: 10 parts of Kochia scoparia, 5 parts of Chrysanthemum morifolium, and 3 parts of Glycyrrhiza uralensis.

[0034] Functional modifiers: 0.3 parts borneol, 0.2 parts menthol, 1 part azone, 1.5 parts panthenol, 2 parts glycerin; Gel matrix: 15 parts poloxamer, 0.5 parts chitosan.

[0035] The oil phase, aqueous phase, formulation ratio, and preparation method of the Chinese herbal extract are the same as those in Example 1.

[0036] Example 3 Prepare the ingredients according to the following proportions: Oil phase of Chinese herbal extracts: 30 parts of *Gnaphalium affine*, 15 parts of *Phellodendron chinense*, and 15 parts of *Senecio scandens*. Aqueous phase of Chinese herbal extracts: 20 parts of Kochia scoparia, 10 parts of Chrysanthemum morifolium, and 10 parts of Glycyrrhiza uralensis.

[0037] Functional modifiers: 0.5 parts borneol, 0.5 parts menthol, 3 parts azone, 2 parts panthenol, 3 parts glycerin; Gel matrix: 20 parts poloxamer, 1.5 parts chitosan.

[0038] The oil phase, aqueous phase, formulation ratio, and preparation method of the Chinese herbal extract are the same as those in Example 1.

[0039] Example 4 The difference from Example 1 is as follows: The composition of the extract consists of 10 parts oil phase, 15 parts aqueous phase, 5 parts polyethylene glycol glyceride oleate, 5 parts medium-chain triglycerides, 20 parts gel matrix, and 8 parts functional regulators.

[0040] The preparation methods for the oil phase, aqueous phase, and external preparation of the traditional Chinese medicine extract are the same as those in Example 1.

[0041] Example 5 The difference from Example 1 is as follows: Five parts of the oil phase of the Chinese herbal extract, ten parts of the aqueous phase of the Chinese herbal extract, three parts of polyethylene glycol oleate, two parts of medium-chain triglycerides, 15 parts of gel matrix, and five parts of functional regulator.

[0042] The preparation methods for the oil phase, aqueous phase, and external preparation of the traditional Chinese medicine extract are the same as those in Example 1.

[0043] Comparative Example 1 The difference from Example 1 is that oleic acid polyethylene glycol glyceride and medium-chain triglycerides are not added when preparing the topical formulation, while the remaining raw material ratios and preparation methods are the same as in Example 1.

[0044] Comparative Example 2 The difference from Example 1 is that no gel matrix is ​​added when preparing the topical formulation, while the other raw material ratios and preparation methods are the same as in Example 1.

[0045] Comparative Example 3 The difference in Example 1 is that, when preparing the topical preparation, the oil phase of the Chinese herbal extract, the aqueous phase of the Chinese herbal extract, and the functional modifier are simply mixed evenly.

[0046] Experimental Example 1. Centrifugation stability test (4000 rpm, 15 min): Place approximately 10 g of sample in a stoppered centrifuge tube, balance it with an analytical balance, and then place it in a centrifuge. Centrifuge at the specified speed and time. After centrifugation, immediately visually observe the sample for any stratification, precipitation, flocculation, or demulsification. No obvious phase separation or precipitation is considered acceptable.

[0047] 2. Heat resistance test (40°C, 30 days): Seal the sample in a vial or simulated packaging and place it in a 40°C constant temperature incubator for 30 days. Take samples on days 0, 10, 20, and 30 for observation. Observe: changes in appearance (color, uniformity), properties (whether it becomes thinner, separates water, or separates oil), and odor, and measure changes in key physicochemical indicators (such as viscosity and pH). The properties should be stable, and the changes in all indicators compared to day 0 should be within acceptable ranges (e.g., viscosity change rate <10%).

[0048] 3. Cold Resistance Test (-20°C, 30 days): Seal the sample and place it in a -20°C freezer for 30 days. Observe on day 0 and day 30 (after returning to room temperature and equilibration). Observe whether the sample freezes, undergoes irreversible crystal form or structural changes (such as becoming rougher or exuding water), and whether it can recover its original properties after returning to room temperature. Standard: After returning to room temperature, the properties are basically restored, with no irreversible damage.

[0049] 4. Viscosity measurement (cPs, 25°C), rotational rheometer (Brookfield DV series). Heat the sample to 25°C, select a suitable rotor model and speed (e.g., RV-6 rotor, 20 rpm), and ensure the torque reading is between 10% and 90% of full scale. Record the stable value.

[0050] 5. Transdermal absorption rate (Franz diffusion cell method): The Franz vertical diffusion cell typically has an effective diffusion area of ​​0.64. Simulated skin: Ex vivo rat skin is commonly used; subcutaneous fat must be removed from the ex vivo skin, and its integrity checked. Receiving solution: Selected based on drug solubility; physiological saline-PBS (containing appropriate amounts of ethanol or surfactants to maintain "leakage conditions") is commonly used.

[0051] Procedure: Secure the skin between the supply chamber and the receiving chamber. Add a quantitative amount of sample to the supply chamber, fill the receiving chamber with the receiving solution and stir magnetically, maintaining a constant temperature of 32±1°C. At predetermined time points (e.g., 2, 4, 6, 8, 12, 24h), remove all the receiving solution and replenish with isothermal fresh solution.

[0052] Detection: The collected receiving liquid was analyzed by HPLC (High Performance Liquid Chromatography) to determine the concentration of a specific active ingredient (berberine hydrochloride).

[0053] Calculation: Based on the concentration, volume, and diffusion area, calculate the cumulative permeation per unit area (Q_n), plot the permeation curve, and the slope of the steady-state portion is the transdermal rate (J_s, unit such as μg / cm²·h).

[0054] 4. pH value determination: Dissolve or disperse an appropriate amount of sample in freshly boiled and cooled distilled water (usually at a ratio of 1:10), stir well, and directly insert the composite electrode at 25°C for measurement.

[0055] 5. Safety Evaluation Model: Healthy domestic rabbits are usually used.

[0056] Method (Draize method): Hair was removed from the back of the animal, and the test area was demarcated. 0.5g of sample was evenly applied to a dressing and placed on intact skin and slightly abraded skin, and covered with gauze for 4 or 24 hours. After removal, the dressing site was observed at 1, 24, 48, and 72 hours.

[0057] Scoring: Based on reactions such as erythema and edema, score according to the Draize scoring system (0-4 points).

[0058] Evaluation: Calculate the Primary Stimulation Index (PII) to determine whether the stimulation is non-irritating, mildly irritating, or strongly irritating.

[0059] 6. Content determination Instrument: High performance liquid chromatograph (HPLC) equipped with a diode array detector (DAD) or mass spectrometer (MS).

[0060] Preparation of test solution: Accurately weigh the sample, extract it with an appropriate solvent (such as methanol-water mixture) using ultrasound, dilute to volume, and filter.

[0061] Preparation of reference solutions: Accurately weigh the reference standards for each target component (alkaloids from *Gnaphalium affine*, berberine from *Phellodendron chinense*, palmatine, etc.) and prepare a series of concentration solutions.

[0062] Chromatographic conditions: Optimize the chromatographic column (e.g., C18 column), mobile phase (e.g., acetonitrile-0.1% phosphoric acid water gradient elution), flow rate, column temperature, and detection wavelength.

[0063] Determination and calculation: Inject samples separately, calculate the content of each component in the sample using the external standard method, and sum them up to obtain the "total content".

[0064] 7. In vitro pharmacodynamic evaluation Strains: Standard strains, such as Staphylococcus aureus (ATCC 6538) and Escherichia coli (ATCC 8739). Activated to the logarithmic growth phase.

[0065] Procedure: Use the spread plate method to evenly distribute the bacterial suspension on Mueller-Hinton agar plates. Make holes in the plate using a sterile punch, or place a quantitative sample in the center of the plate using a sterile swab.

[0066] Incubation: After pre-diffusion for a period of time with the plate upright, incubate upside down in a 37°C constant temperature incubator for 18-24 hours.

[0067] Measurement: Measure the diameter of the inhibition zone (including the pore or the sample itself) using vernier calipers, accurate to 0.1 mm. Take the average of three replicates.

[0068] The test results are shown in Table 1.

[0069] Table 1

[0070] Table 1 shows that Example 1 exhibits excellent and balanced performance across all aspects, with superior stability, transdermal penetration, and user experience. Example 2, due to reduced amounts of functional modifiers (especially the penetration enhancer azone) and gel matrix, resulted in decreased transdermal absorption and slightly poorer high-temperature stability, demonstrating that sufficient amounts of penetration enhancers and matrix are crucial for efficacy and stability. Example 3 has a high content of herbal extract, resulting in the highest concentration of active ingredients and antibacterial activity; however, it also exhibits increased viscosity and may cause mild skin irritation due to its stronger medicinal properties.

[0071] Comparative Example 1 (without oil-phase solubilizer): Oil-water separation occurred, resulting in extremely low transdermal absorption. Polyethylene glycol oleate and medium-chain triglycerides play crucial roles as solubilizers and carriers, forming the core of a stable nanoemulsion / gel system.

[0072] Comparative Example 2 (without gel matrix): The product is a liquid, which cannot adhere to the skin, making it inconvenient to use and unstable. The transdermal effect cannot be sustained due to rapid loss.

[0073] Comparative Example 3 (simple mixing): Poor stability and transdermal absorption. Simple physical mixing cannot achieve stable delivery of active ingredients.

[0074] The embodiments described above are some, but not all, embodiments of the present invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

Claims

1. An antibacterial and anti-inflammatory topical preparation, characterized in that, By weight, it includes 5-10 parts of the oil phase of the Chinese herbal extract, 10-15 parts of the aqueous phase of the Chinese herbal extract, 3-5 parts of polyethylene glycol glyceride oleate, 2-5 parts of medium-chain triglycerides, 15-20 parts of gel matrix, and 5-8 parts of functional regulator. By weight, the oil phase of the herbal extract includes the following raw materials: 20-30 parts of *Gentiana scabra*, 5-15 parts of *Phellodendron chinense*, and 5-15 parts of *Senecio scandens*. By weight, the aqueous phase of the herbal extract comprises the following raw materials: 10-20 parts of Kochia scoparia, 5-10 parts of Chrysanthemum morifolium, and 3-10 parts of Glycyrrhiza uralensis.

2. The antibacterial and anti-inflammatory topical preparation according to claim 1, characterized in that, The oil phase of the traditional Chinese medicine extract includes the following raw materials: 20 parts of *Gentiana scabra*, 8 parts of *Phellodendron chinense*, and 5 parts of *Senecio scandens*. By weight, the aqueous phase of the herbal extract comprises the following raw materials: 10 parts of Kochia scoparia, 5 parts of Chrysanthemum morifolium, and 3 parts of Glycyrrhiza uralensis.

3. The antibacterial and anti-inflammatory topical preparation according to claim 1, characterized in that, The oil phase of the herbal extract includes the following raw materials: 30 parts of Gallnut, 15 parts of Phellodendron bark, and 15 parts of Senecio scandens. By weight, the aqueous phase of the herbal extract comprises the following raw materials: 20 parts of Kochia scoparia, 10 parts of Chrysanthemum morifolium, and 10 parts of Glycyrrhiza uralensis.

4. The antibacterial and anti-inflammatory topical preparation according to claim 1, characterized in that, By weight, the functional modifier comprises: 0.3-0.5 parts borneol, 0.2-0.5 parts menthol, 1-3 parts azone, 1.5-2 parts panthenol, and 2-3 parts glycerin.

5. The antibacterial and anti-inflammatory topical preparation according to claim 1, characterized in that, The gel matrix comprises the following raw materials in parts by weight: 15-20 parts poloxamer and 0.5-1.5 parts chitosan.

6. A method for preparing an antibacterial and anti-inflammatory topical preparation as described in any one of claims 1-5, characterized in that, Includes the following steps: S1, preparing the oil phase and aqueous phase of the traditional Chinese medicine extract; S2, mix the oil phase of the Chinese herbal extract, polyethylene glycol oleate, medium-chain triglycerides, and functional regulators, and stir in a water bath at 50-60℃ until completely clear to obtain the nano oil phase; S3, In an ice-water bath, poloxamer is added to water and magnetically stirred until homogeneous to obtain poloxamer solution; Chitosan was dissolved in acetic acid-containing water, and then the aqueous phase of the traditional Chinese medicine extract was added and mixed evenly to obtain a mixture. Add the mixture to the poloxamer solution while stirring in an ice water bath, and stir until homogeneous; A gel aqueous phase was obtained; S4. Under high-speed shearing, the nano oil phase is added to the gel aqueous phase, followed by high-speed shearing for 5-10 minutes and vacuum degassing to obtain the topical preparation.

7. The method for preparing the antibacterial and anti-inflammatory topical preparation according to claim 6, characterized in that, The method for preparing the oil phase of the traditional Chinese medicine extract includes the following steps: The medicinal materials were pulverized into coarse powder and placed in an extraction vessel for supercritical CO2 extraction for 2-3 hours. The extract was then separated in two stages to obtain the crude oil phase. Add anhydrous sodium sulfate to the crude oil phase, stir to dehydrate, and filter; Add glycerol, stir and reflux at 85-90℃ for 30-40 minutes, centrifuge, and take the supernatant oil layer to obtain the oil phase of the Chinese herbal extract.

8. The method for preparing the antibacterial and anti-inflammatory topical preparation according to claim 7, characterized in that, The conditions for supercritical CO2 extraction are: pressure: 25-35 MPa, temperature: 45-55℃; CO2 flow rate: 20-30 L / h.

9. The method for preparing the antibacterial and anti-inflammatory topical preparation according to claim 6, characterized in that, The method for preparing the aqueous phase of the traditional Chinese medicine extract includes the following steps: Place all medicinal materials into an extraction tank, add 8-10 times the volume of water, and soak for 30-4 minutes; heat to boiling, maintain a gentle boil, and reflux for 1-1.5 hours; filter and collect the first decoction; add 8 volumes of water to the residue, reflux for 1-1.5 hours, filter, and collect the second decoction; combine the decoctions, transfer to a vacuum concentration tank, and concentrate to 1 / 5 of the original volume to obtain a concentrated solution; While stirring, add 95% ethanol to the concentrate to make the alcohol content reach 60%-65%; continue stirring for 20-30 minutes, let stand at 4°C for 24 hours, collect the supernatant, recover the ethanol in the supernatant until the supernatant has no alcohol odor, then refine it with macroporous adsorption resin, and vacuum concentrate it into a thick paste to obtain the aqueous phase of the Chinese herbal extract.

10. The method for preparing the antibacterial and anti-inflammatory topical preparation according to claim 9, characterized in that, At 60°C, the relative density of the aqueous phase of the herbal extract is 1.25-1.35.

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