A kind of external-use medicine for incontinence dermatitis and preparation method thereof

Abstract

The present invention provides an external-use medicine for incontinence dermatitis and a preparation method thereof. The external-use medicine comprises 20-35 parts of modified grapefruit oil, 10-20 parts of a biodegradable film-forming polymer, 5-10 parts of a composite anti-inflammatory agent, 8-15 parts of an astringent, 5-15 parts of an emulsifier, and 3-10 parts of a moisturizer, wherein the composite anti-inflammatory agent contains a composite extract of Torreya grandis, Alpinia oxyphylla, and Lygodium japonicum in a specific mass ratio. The modified grapefruit oil is extracted by multiple steps such as crushing, enzymatic hydrolysis, pulsed electric field, and high-voltage microfluidization; the composite anti-inflammatory agent has its specific water immersion ultrasonic extraction method; and each raw material component such as the biodegradable film-forming polymer and the astringent also has a clear composition. Its preparation method covers the steps of raw material processing, ultrasound-assisted fusion, adding other ingredients and stirring, and can eventually be made into a spray, gel, or cream dosage form. The present invention integrates a variety of natural and functional ingredients to provide an effective external-use medicine for the treatment of incontinence dermatitis, which is expected to improve the patient's skin symptoms and promote skin repair.

Description

Technical Field

[0001] The present invention relates to the technical field of medicine, and in particular to an external-use medicine for incontinence dermatitis and a preparation method thereof. Background Art

[0002] Incontinence dermatitis ( Incontinence-Associated Dermatitis Incontinent skin disease (IAD) is a common skin problem that has long plagued caregivers and patients, particularly the elderly, paralyzed patients, and those suffering from neurological disorders that lead to incontinence. Incontinence causes prolonged exposure of the skin to excretions such as urine and feces. The irritants contained in these excretions can disrupt the skin's barrier function, triggering a series of inflammatory reactions such as redness, itching, pain, ulceration, and exudation. This not only causes significant pain to patients but also increases the risk of complications such as infection, severely impacting their quality of life and recovery.

[0003] Currently, topical medications are often used in the treatment of incontinence dermatitis. The existing topical medications for incontinence dermatitis have the following deficiencies:

[0004] (1) Drug ingredients and efficacy

[0005] Limited anti-inflammatory effect: Although most existing topical medications have certain anti-inflammatory effects, their ability to inhibit the production of inflammatory factors and alleviate inflammatory responses is not ideal in the face of the complex inflammatory mechanism of incontinence dermatitis and continuous inflammatory stimulation. It is often difficult to quickly and effectively relieve inflammatory symptoms such as skin redness, swelling, and pain, which makes skin inflammation last longer and delays the overall recovery process.

[0006] Insufficient astringent effect: In dealing with the skin exudation problem that often occurs in incontinence dermatitis, existing drugs have poor astringent ability and cannot reduce exudate in time, causing the skin to be in a humid environment for a long time, further damaging the skin barrier, making it easier for bacteria to grow, aggravating skin damage, and not conducive to subsequent skin repair.

[0007] Weak skin repair function: After the skin is damaged by incontinence dermatitis, effective drugs are needed to promote its repair and regeneration. However, some existing topical drugs are not effective enough in stimulating skin cell proliferation, accelerating wound healing, and improving skin tissue structure to promote skin repair, resulting in slow skin healing and even leaving obvious scars and other adverse consequences.

[0008] (2) Drug dosage form and ease of use

[0009] Large dosage form limitations: Common dosage forms on the market, such as traditional ointments and lotions, each have their own drawbacks. Ointments can be thick and heavy, resulting in poor skin permeability after application, which can affect normal skin metabolism. Lotions have a short duration of action and require frequent use, which can be inconvenient for nursing care. They also provide insufficient coverage and protection for broken skin, failing to effectively isolate the skin from the constant irritation of excrement.

[0010] Poor film-forming properties: Some topical medications are difficult to form a stable, long-lasting protective film with good barrier properties on the skin surface after use. They cannot effectively prevent urine, feces, etc. from contacting and irritating the skin again, reducing the drug's protective and therapeutic effects on the skin. Frequent reapplication of the drug is required, increasing the nursing workload and patient discomfort.

[0011] (3) Drug raw materials and safety

[0012] Insufficient utilization of natural ingredients: Existing drugs mostly focus on the use of chemically synthesized ingredients. Although they can solve symptoms to a certain extent, some chemicals may have potential risks of skin irritation or adverse reactions. Some ingredients such as natural plant extracts with good anti-inflammatory, astringent, and repair effects have not been fully explored and reasonably utilized, making it difficult to meet patients' expectations for drug safety and mildness.

[0013] Lack of consideration for biocompatibility: Some drugs pay little attention to biocompatibility with human skin when selecting raw materials, which may lead to allergies, intolerance, etc. after drug use, which is not conducive to long-term use. In particular, for diseases such as incontinence dermatitis that require continuous medication, biocompatibility issues should be given more attention.

[0014] In view of the above-mentioned shortcomings of existing topical medications for incontinence dermatitis, there is an urgent need to develop a new topical medication that not only has good comprehensive effects such as anti-inflammatory, astringent and skin repair, but also has a suitable dosage form for easy use, while making full use of natural ingredients to improve safety and biocompatibility, so as to more effectively treat incontinence dermatitis, improve patients' skin condition, and improve patients' quality of life. Summary of the Invention

[0015] In view of this, the present invention provides an external-use medicine for incontinence dermatitis and a preparation method thereof to solve the above problems.

[0016] The technical solution of the present invention is achieved as follows: an external-use medicine for incontinence dermatitis comprises the following raw materials in parts by weight: 20-35 parts of improved grapefruit oil, 10-20 parts of a biodegradable film-forming polymer, 5-10 parts of a composite anti-inflammatory agent, 8-15 parts of an astringent, 5-15 parts of an emulsifier, and 3-10 parts of a moisturizer; the composite anti-inflammatory agent comprises a composite extract of Torreya grandis, Alpinia oxyphylla, and Lygodium japonicum in a mass ratio of (5-13):(2-10):(1-3).

[0017] Furthermore, a composite anti-inflammatory agent for incontinence dermatitis comprises the following raw materials in parts by weight: 28 parts of modified grapefruit oil, 15 parts of biodegradable film-forming polymer, 8 parts of composite anti-inflammatory agent, 12 parts of astringent, 10 parts of emulsifier, and 7 parts of moisturizer.

[0018] Furthermore, the extraction method of the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata is to select high-quality, dry and mildew-free Torreya grandis branches and leaves and dry, plump Alpinia oxyphylla and Lycopodiella ternata branches and leaves, crush them to 20-30 mesh, soak and extract them with water for 3-5 hours, add extraction solvent for ultrasonic extraction, the mass volume ratio of the mixed powder and the extraction solvent is 1:8-12, the extraction solvent is anhydrous ethanol, ethyl acetate and water in a volume ratio of 4-6:1-3:20, the ultrasonic frequency is 20-40kHz, the ultrasonic power is 300-500W, the ultrasonic time is 30-60min, and the temperature during ultrasonic extraction is controlled at 40-50°C to obtain the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata.

[0019] Furthermore, the extraction method of the improved grapefruit oil is:

[0020] (1) Crushing: Take mature, non-deteriorated grapefruit seeds, screen and remove impurities, and crush them into 20-40 mesh;

[0021] (2) Enzymatic hydrolysis: the crushed grapefruit seeds were mixed with water at a mass volume ratio of 25-35:100, the pH value was adjusted to 6-8, and then an enzyme preparation was added at a mass ratio of 2-5% of the grapefruit seeds, and enzymatic hydrolysis was performed at 25-30°C for 3-8 hours. The enzyme preparation was a protease, an amylase, and a pectinase at a mass ratio of 1:1-3:3-5 to destroy the cell wall and cell membrane of the grapefruit seeds, release the oil, and centrifuge to obtain oil I;

[0022] (3) Pulsed electric field treatment: The crude oil is placed in a pulsed electric field treatment device and treated with a pulsed direct current electric field for 20-50 min, with a pulse frequency of 2.3-2.7 kHz, a voltage of 10-50 V, a pulse width of 20-50 μs, and a pulse number of 15-30 times; under the action of the pulsed electric field, the permeability of the grapefruit seed cells increases, making it easier for the oil to seep out of the cells, thereby increasing the oil yield and obtaining oil II;

[0023] (4) High-pressure microfluidization treatment: Oil II is subjected to high-pressure microfluidization treatment 2-5 times, each time for 15-25 minutes, at a treatment pressure of 100-500 MPa and a flow rate of 5-10 mL / min. The treated oil is filtered and centrifuged for purification to obtain the improved grapefruit oil. This further breaks down and separates the tiny particles and impurities in the oil, which helps to improve the purity and stability of the oil.

[0024] Furthermore, the biodegradable film-forming polymer comprises polylactic acid-glycolic acid copolymer and trimethylsiloxysilicate in a mass ratio of 1:1-3.

[0025] Furthermore, the astringent is a mixture of metal ion chelating agent disodium edetate, gallnut tannin and gallic acid in a mass ratio of (3-7): (8-15): (2-6).

[0026] Furthermore, the emulsifier is selected from any one or a combination of propylene glycol, glycerin, sodium lauryl sulfate, sodium carboxymethyl cellulose and polysorbate 80.

[0027] Furthermore, the moisturizing agent is a mixture of sodium hyaluronate and ceramide in a mass ratio of 2:1-2.

[0028] Furthermore, a method for preparing a compound anti-inflammatory drug for incontinence dermatitis comprises the following steps:

[0029] S1. Ultrafinely pulverize the composite anti-inflammatory agent and the astringent to a particle size of 1-10 μm, and then mix them uniformly to obtain an active mixed powder;

[0030] S2. Slowly add the extracted grapefruit oil to the active mixed powder under ultrasound-assisted conditions at a frequency of 20-40 kHz and continue ultrasonic stirring for 30-60 minutes to allow for full integration;

[0031] S3. Add a biodegradable film-forming polymer, an emulsifier, and a moisturizer to the above system in sequence, stir for 2-5 hours at a constant temperature of 35-45°C and a stirring speed of 400-600 rpm, until a uniform semi-fluid finished drug product is formed, and then prepare it into a spray form, a gel form, or a cream form to obtain an external-use drug for incontinence dermatitis.

[0032] Furthermore, the ultrasonic treatment in S2 is performed intermittently, with a 2-minute pause after every 10 minutes of ultrasonic treatment, to prevent local overheating from affecting the stability of the active ingredients and ensure that the ingredients are evenly dispersed and their activity is not impaired.

[0033] Compared with the prior art, the present invention has the following beneficial effects.

[0034] The composite extracts of Torreya grandis, Alpinia oxyphylla and Lycopodiella cava in a specific mass ratio contained in the composite anti-inflammatory agent for incontinence dermatitis of the present invention can synergistically exert an excellent anti-inflammatory effect, effectively inhibit the production and release of inflammatory factors, quickly relieve symptoms such as skin redness, swelling and pain, shorten the duration of inflammation, and reduce the risk of complications; the astringent composed of specific ingredients has a good astringent effect, can timely reduce skin exudate, maintain the skin barrier function, avoid further damage by excreta and facilitate repair. After being extracted through multiple fine processes, the improved grapefruit oil is rich in a variety of nutrients beneficial to the skin, and synergizes with other ingredients to significantly promote skin repair, accelerate wound healing, improve skin tissue structure and reduce scar formation. The biodegradable film-forming polymer can form a stable protective film with good barrier properties and good breathability on the skin surface, isolate excreta stimulation, reduce the frequency of medication, and improve comfort and therapeutic effects.

[0035] The entire preparation process is optimized through modern preparation technologies such as ultrafine grinding, ultrasound-assisted mixing, and constant temperature stirring, ensuring the drug's effectiveness and safety. It can be formulated into a variety of dosage forms, including sprays, gels, and creams, to meet diverse usage needs and clinical care scenarios, enhancing ease of use. Furthermore, the drug utilizes a variety of natural plant extracts as its primary ingredients, combined with proven safety excipients, offering a high degree of safety and good biocompatibility, making it suitable for long-term use. It provides a comprehensive, safe, reliable, convenient, and effective solution for the treatment of incontinence dermatitis, with significant clinical application value and social benefits. DETAILED DESCRIPTION

[0036] In order to better understand the technical content of the present invention, specific examples are provided below to further illustrate the present invention.

[0037] Unless otherwise specified, the experimental methods used in the examples of the present invention are all conventional methods.

[0038] Unless otherwise specified, the materials, reagents, etc. used in the examples of the present invention can be obtained from commercial sources. Example 1

[0039] A topical medicament for incontinence dermatitis comprises the following raw materials in parts by weight: 20 parts of modified grapefruit oil, 10 parts of a biodegradable film-forming polymer, 5 parts of a composite anti-inflammatory agent, 8 parts of an astringent, 5 parts of an emulsifier, and 3 parts of a moisturizer.

[0040] The biodegradable film-forming polymer comprises polylactic acid-glycolic acid copolymer and trimethylsiloxysilicate in a mass ratio of 1:1.

[0041] The composite anti-inflammatory agent comprises composite extracts of Torreya grandis, Alpinia oxyphylla and Lygodium japonicum in a mass ratio of 5:2:1.

[0042] The extraction method of the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata is as follows: high-quality, dry and mildew-free Torreya grandis branches and leaves and dry, plump Alpinia oxyphylla and Lycopodiella ternata branches and leaves are selected, crushed to 20 meshes, soaked and extracted with water for 3 hours, and an extraction solvent is added for ultrasonic extraction, the mass volume ratio of the mixed powder and the extraction solvent is 1:8, the extraction solvent is anhydrous ethanol, ethyl acetate and water in a volume ratio of 4:1:20, the ultrasonic frequency is 20 kHz, the ultrasonic power is 300 W, the ultrasonic time is 30-60 min, and the temperature during ultrasonic extraction is controlled at 40°C to obtain the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata.

[0043] The astringent is a mixture of metal ion chelating agent disodium edetate, gallnut tannin and gallic acid in a mass ratio of 3:8:2.

[0044] The emulsifier is selected from propylene glycol.

[0045] The moisturizing agent is a mixture of sodium hyaluronate and ceramide in a mass ratio of 2:1.

[0046] The extraction method of the improved grapefruit oil:

[0047] (1) Crushing: Take mature, non-deteriorated grapefruit seeds, screen and remove impurities, and crush them into 20 mesh;

[0048] (2) Enzymatic hydrolysis: The crushed grapefruit seeds were mixed with water at a mass volume ratio of 25:100, and the pH value was adjusted to 6. Then, an enzyme preparation (2% by mass of the grapefruit seeds) was added, and enzymatic hydrolysis was performed at 25°C for 3 h. The enzyme preparation comprised protease, amylase, and pectinase at a mass ratio of 1:1:3. The mixture was centrifuged to obtain oil I.

[0049] (3) Pulsed electric field treatment: The crude oil was placed in a pulsed electric field treatment device and treated with a pulsed DC electric field for 20 min at a pulse frequency of 2.3 kHz, a voltage of 10 V, a pulse width of 20 μs, and 15 pulses to obtain oil II.

[0050] (4) High-pressure microfluidization treatment: The oil II was subjected to high-pressure microfluidization treatment twice, each time for 15 min, with a treatment pressure of 100 MPa and a flow rate of 5 mL / min. The oil was filtered and centrifuged for purification to obtain improved grapefruit oil. Example 2

[0051] A topical medicament for incontinence dermatitis comprises the following raw materials in parts by weight: 35 parts of modified grapefruit oil, 20 parts of a biodegradable film-forming polymer, 10 parts of a composite anti-inflammatory agent, 15 parts of an astringent, 15 parts of an emulsifier, and 10 parts of a moisturizer.

[0052] The biodegradable film-forming polymer comprises polylactic acid-glycolic acid copolymer and trimethylsiloxysilicate in a mass ratio of 1:3.

[0053] The composite anti-inflammatory agent comprises composite extracts of Torreya grandis, Alpinia oxyphylla and Lygodium japonicum in a mass ratio of 13:10:3.

[0054] The extraction method of the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata is as follows: high-quality, dry and mildew-free Torreya grandis branches and leaves, dry and plump Alpinia oxyphylla and Lycopodiella ternata branches and leaves are selected, crushed to 30 meshes, soaked and extracted with water for 5 hours, and an extraction solvent is added for ultrasonic extraction, the mass volume ratio of the mixed powder and the extraction solvent is 1:12, the extraction solvent is anhydrous ethanol, ethyl acetate and water in a volume ratio of 6:3:20, the ultrasonic frequency is 40kHz, the ultrasonic power is 500W, the ultrasonic time is 60min, and the temperature during ultrasonic extraction is controlled at 50°C to obtain the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata.

[0055] The astringent is a mixture of metal ion chelating agent disodium edetate, gallnut tannin and gallic acid in a mass ratio of 7:15:6.

[0056] The emulsifier is selected from sodium lauryl sulfate.

[0057] The moisturizing agent is a mixture of sodium hyaluronate and ceramide in a mass ratio of 2:2.

[0058] The extraction method of the improved grapefruit oil:

[0059] (1) Crushing: Take mature, non-deteriorated grapefruit seeds, screen and remove impurities, and crush them into 20-40 mesh;

[0060] (2) Enzymatic hydrolysis: The crushed grapefruit seeds were mixed with water at a mass volume ratio of 35:100, and the pH value was adjusted to 8. Then, an enzyme preparation (5% by mass of the grapefruit seeds) was added, and enzymatic hydrolysis was performed at 30°C for 3-8 hours. The enzyme preparation comprised protease, amylase, and pectinase at a mass ratio of 1:3:5. The mixture was centrifuged to obtain oil I.

[0061] (3) Pulsed electric field treatment: The crude oil was placed in a pulsed electric field treatment device and treated with a pulsed DC electric field for 50 min at a pulse frequency of 2.7 kHz, a voltage of 50 V, a pulse width of 50 μs, and 30 pulses to obtain oil II.

[0062] (4) High-pressure microfluidization treatment: The oil II was subjected to high-pressure microfluidization treatment 5 times, each time for 25 min, with a treatment pressure of 500 MPa and a flow rate of 10 mL / min. The oil was filtered and centrifuged for purification to obtain improved grapefruit oil. Example 3

[0063] A topical medicament for incontinence dermatitis comprises the following raw materials in parts by weight: 28 parts of modified grapefruit oil, 15 parts of a biodegradable film-forming polymer, 8 parts of a composite anti-inflammatory agent, 12 parts of an astringent, 10 parts of an emulsifier, and 7 parts of a moisturizer.

[0064] The biodegradable film-forming polymer comprises polylactic acid-glycolic acid copolymer and trimethylsiloxysilicate in a mass ratio of 1:2.

[0065] The composite anti-inflammatory agent comprises composite extracts of Torreya grandis, Alpinia oxyphylla and Lygodium japonicum in a mass ratio of 8:6:2.

[0066] The extraction method of the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata is as follows: high-quality, dry and mildew-free Torreya grandis branches and leaves and dry, plump Alpinia oxyphylla and Lycopodiella ternata branches and leaves are selected, crushed to 25 meshes, soaked and extracted with water for 4 hours, and an extraction solvent is added for ultrasonic extraction, the mass volume ratio of the mixed powder and the extraction solvent is 1:10, the extraction solvent is anhydrous ethanol, ethyl acetate and water in a volume ratio of 5:2:20, the ultrasonic frequency is 30kHz, the ultrasonic power is 400W, the ultrasonic time is 50min, and the temperature during ultrasonic extraction is controlled at 45°C to obtain the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata.

[0067] The astringent is a mixture of metal ion chelating agent disodium edetate, gallnut tannin and gallic acid in a mass ratio of 5:12:4.

[0068] The emulsifier is selected from sodium carboxymethylcellulose and polysorbate 80.

[0069] The moisturizing agent is a mixture of sodium hyaluronate and ceramide in a mass ratio of 2:1.

[0070] The extraction method of the improved grapefruit oil:

[0071] (1) Crushing: Take mature, non-deteriorated grapefruit seeds, screen and remove impurities, and crush them into 30 mesh;

[0072] (2) Enzymatic hydrolysis: The crushed grapefruit seeds were mixed with water at a mass volume ratio of 30:100, and the pH value was adjusted to 7. Then, an enzyme preparation (3% by mass of the grapefruit seeds) was added, and enzymatic hydrolysis was performed at 28°C for 5 h. The enzyme preparation contained protease, amylase, and pectinase at a mass ratio of 1:2:4. The mixture was centrifuged to obtain oil I.

[0073] (3) Pulsed electric field treatment: The crude oil was placed in a pulsed electric field treatment device and treated with a pulsed DC electric field for 35 min at a pulse frequency of 2.5 kHz, a voltage of 30 V, a pulse width of 35 μs, and 25 pulses to obtain oil II.

[0074] (4) High-pressure microfluidization treatment: The oil II was subjected to high-pressure microfluidization treatment three times, each time for 20 min, with a treatment pressure of 300 MPa and a flow rate of 8 mL / min. The oil was filtered and centrifuged for purification to obtain improved grapefruit oil.

[0075] The above examples 1-3 adopt the following preparation method:

[0076] S1. Ultrafinely pulverize the composite anti-inflammatory agent and the astringent to a particle size of 6 μm, and then mix them uniformly to obtain an active mixed powder;

[0077] S2. Slowly add the extracted grapefruit oil to the active mixed powder under ultrasound-assisted conditions at a frequency of 30 kHz and continue ultrasonic stirring for 50 minutes to allow for full integration;

[0078] S3. Add a biodegradable film-forming polymer, an emulsifier, and a moisturizer to the above system in sequence, and stir for 3 hours at a constant temperature of 40°C and a stirring speed of 500 rpm until a uniform semi-fluid drug product is formed, and then prepare it into a spray form, a gel form, or a cream form to obtain an external-use drug for incontinence dermatitis.

[0079] Comparative Example 1

[0080] The difference between this comparative example and Example 3 is that the external-use medicine for incontinence dermatitis comprises the following raw materials in parts by weight: 15 parts of modified grapefruit oil, 8 parts of biodegradable film-forming polymer, 15 parts of composite anti-inflammatory agent, 7 parts of astringent, 20 parts of emulsifier, and 2 parts of moisturizer.

[0081] Comparative Example 2

[0082] The difference between this comparative example and Example 3 is that the grapefruit oil used in the external medicament for incontinence dermatitis is not treated with a pulsed electric field.

[0083] Comparative Example 3

[0084] The difference between this comparative example and Example 3 is that the composite anti-inflammatory agent in the raw materials of the external-use medicament for incontinence dermatitis is mupirocin, erythromycin and chlortetracycline in a mass ratio of 8:6:2.

[0085] Comparative Example 4

[0086] The difference between this comparative example and Example 3 is that the astringent in the raw materials of the external-use medicament for incontinence dermatitis is tannic acid.

[0087] 1. Validation

[0088] Test Example 1-Verification of Convergence

[0089] 1. Prepare simulated skin exudate using a solution containing bovine serum albumin (BSA, 1% concentration), sodium chloride (0.9% concentration to simulate physiological concentration), and buffer (phosphate buffer, pH 7.2-7.4) to simulate the protein and electrolyte components of wound exudate.

[0090] 2. Dilute the test drug with normal saline to 1 / 4 of the original drug concentration. At the same time, set up a positive control (5% tannic acid solution) and a blank control (a solution containing only simulated exudate).

[0091] 3. Operation steps.

[0092] Take equal volumes (5 mL) of the test drug solution, positive control solution, and blank control solution of each experimental group and add them to the corresponding stoppered test tubes. Then add equal amounts (5 mL) of simulated skin exudate to each test tube, mix thoroughly, and let it stand at room temperature for observation.

[0093] At time points such as 15 minutes, 30 minutes, and 60 minutes, the turbidity of the solution in each test tube was observed. The absorbance was measured using a spectrophotometer at a specific wavelength (620 nm, at which protein precipitation exhibits a significant change in light absorption). Lower absorbance values ​​indicate clearer solutions, more precipitated protein, and greater astringency. The data from the drug groups at different concentrations were compared with the positive control and blank controls to analyze the drug's astringency and effective concentration range.

[0094] Table 1: Absorbance values ​​of each drug group and control group at each time point (wavelength 620nm)

[0095]

[0096] It can be seen from the above absorbance data that, with the passage of time, the absorbance values ​​of each drug treatment group and the positive control group showed a downward trend compared with the blank control group, which indicates that each treatment group has a certain convergent effect, causing the protein in the simulated exudate to precipitate and the solution gradually becomes clear.

[0097] Test Example 2-Anti-inflammatory Effect Test

[0098] 1. Establishment of Cellular Inflammation Model and Drug Treatment

[0099] Cell culture: Mouse macrophage cell line RAW264.7 was selected and cultured in DMEM high-glucose medium containing 10% fetal bovine serum and 1% penicillin-streptomycin in a cell culture incubator at 37°C and 5% CO2. Subsequent experiments were performed after the cells reached the logarithmic growth phase.

[0100] Induction of inflammation: cells were plated at a density of 1 × 10 5Cells were seeded with 1 μg / mL of lipopolysaccharide (LPS) in 96-well plates or culture dishes. After culturing for 24 hours, lipopolysaccharide (LPS, final concentration of 1 μg / mL) was added to induce inflammatory response in the cells to construct an in vitro inflammatory model.

[0101] Drug intervention: Dilute the test drug to a concentration of 10 μg / mL in serum-free culture medium. Add the drug solution of the experimental group to the cells after inflammation induction. At the same time, set up a positive control group (dexamethasone) and a blank control group (only add the inflammation inducer and culture medium, without drug). Set up multiple replicate wells (e.g., 6 replicate wells) for each group and continue to culture for 24-48 hours.

[0102] 2. Inflammatory factor detection

[0103] Cell supernatant collection: After the culture is completed, collect the cell culture supernatant from each well and transfer it to a sterile centrifuge tube. It can be tested immediately or stored in a -80℃ refrigerator for later use.

[0104] Enzyme-linked immunosorbent assay (ELISA): ELISA kits were used according to the manufacturer's instructions to measure the levels of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)) in the supernatant. The absorbance of each well at the corresponding wavelength was read using a microplate reader, and the specific concentration of the inflammatory factors was calculated based on the standard curve. The differences in inflammatory factor concentrations between each drug group and the positive and blank controls were compared. Lower inflammatory factor concentrations indicate a stronger inhibitory effect of the drug, thereby assessing the drug's anti-inflammatory effect and effective anti-inflammatory concentration range.

[0105] Table 2: Concentrations of inflammatory factors in cell culture supernatants (unit: pg / mL)

[0106]

[0107] From the above data, it can be seen that under the induction of lipopolysaccharide, the cells in the blank control group secreted a large amount of inflammatory factors, and the concentrations of TNF-α, IL-6 and IL-1β were at a high level.

[0108] After the positive control group was treated with dexamethasone, the concentrations of various inflammatory factors were significantly reduced, indicating that dexamethasone played a strong anti-inflammatory role in this model and effectively inhibited the inflammatory response.

[0109] The concentrations of various inflammatory factors in the Example group showed a gradual downward trend compared to the blank control group. Although slightly higher than the positive control group, they were still significantly lower than the blank control group, indicating that the drugs or treatment methods represented by the Examples have a significant inhibitory effect on the secretion of the inflammatory factor TNF-α. Similarly, for the two inflammatory factors IL-6 and IL-1β, the concentrations of each group in the Example were also lower than those in the blank control group, reflecting the inhibitory effect on the secretion of these two inflammatory factors, indicating that the drugs in the Example have certain anti-inflammatory capabilities and can intervene in the cellular inflammatory response to a certain extent and reduce the degree of inflammation.

[0110] Test Example 3-Skin Repair Effect Test

[0111] Cell proliferation test (in vitro): Keratinocytes are cultured and treated with drugs. Cell proliferation is then measured using a cell proliferation assay (BrdU incorporation assay). The number or proportion of BrdU-positive cells is measured. A higher number of positive cells indicates more active cell proliferation. This is used to assess the potential effect of drugs in promoting skin cell proliferation and thus skin repair.

[0112] Experimental groups

[0113] Blank control group: contains only culture medium without drugs.

[0114] Positive control group: epidermal growth factor, concentration was 10 ng / mL.

[0115] Drug group: concentration was 10 μg / mL.

[0116] Table 3: Proportion of BrdU-positive cells in different groups

[0117]

[0118] The proportion of BrdU-positive cells in the blank control group was only 12.5±1.2%, which indicates that without the addition of additional drugs to promote cell proliferation, the cells are in a normal basal proliferation state with relatively low proliferation activity. This indicates that under this in vitro culture system, the natural cell proliferation rate is slow, which indirectly reflects that normal skin cells have limited self-repair ability without external intervention.

[0119] The positive control group, using the clinically commonly used epidermal growth factor (at a concentration of 10 ng / mL), showed a BrdU-positive cell ratio of 38.2±2.5%, significantly higher than the blank control group. This demonstrates that epidermal growth factor, as an effective cell proliferation factor, can significantly stimulate skin-related cells in vitro.

[0120] The groups represented by the Example group had BrdU-positive cell ratios of 36.8±2.0%, 36.5±2.0%, and 37.5±2.2%, respectively, all close to those of the positive control group. This means that the drugs or treatments involved in the Examples have a good effect in promoting skin cell proliferation, and their ability to promote cell proliferation is similar to that of the positive control drug. They have a strong potential for skin repair and can significantly increase cell proliferation activity, thereby potentially accelerating the process of skin repair. This indicates that the Example group exhibits advantages comparable to those of the positive control drug at the in vitro cell level, and it can be inferred that they will have a positive promoting effect on skin repair in practical applications.

[0121] The comparative example group showed a certain gap compared to both the example group and the positive control group. This reflects that the drug or treatment represented by the comparative example is less effective than the example group in promoting skin cell proliferation, which means that its potential promotion effect on skin repair is relatively weak. Under the same in vitro experimental conditions, its ability to stimulate cell proliferation is limited. This indicates that after optimization and adjustment, the example group can better play its role in promoting skin repair.

[0122] 2. Typical Cases

[0123] Case 1

[0124] Patient Profile: Ms. Zhang, 72, suffered a stroke and was bedridden for a long time. She was unable to take care of herself and suffered from incontinence. During her care, she developed redness and itching on her buttocks and perineum, followed by small ulcers with significant exudate. A doctor diagnosed her with incontinence-related dermatitis.

[0125] Treatment process: Medical staff selected the topical medication for incontinence dermatitis according to Example 3 of the present invention and prepared it into a cream formulation. After cleaning the patient's skin, the cream was applied to the affected skin three times daily, using gentle movements and using a breathable nursing pad to keep the skin relatively dry.

[0126] Treatment Effect: After one week of medication, skin exudate was significantly reduced, the area of ​​redness and swelling was reduced, and the patient reported less itching. After two weeks of continued use, the ulcers began to scab and heal, and the skin color gradually returned to normal, indicating complete recovery. A further one-month observation period revealed no recurrence, and the skin appeared healthier than before.

[0127] Case 2

[0128] Basic information of the patient: Mr. Li, 58 years old, suffered spinal cord injury and lower limb paralysis due to a car accident. He needed a long-term indwelling urinary catheter, but still had occasional urine leakage, resulting in incontinence dermatitis on the inner thighs and scrotum, manifested as large areas of skin flushing, accompanied by pain, and signs of erosion in some areas.

[0129] Treatment process: The incontinence dermatitis topical spray drug of Example 3 of the present invention was used for treatment. The patient's skin was first disinfected and cleaned, and then the drug was evenly sprayed 10-15 cm away from the skin, four times a day, each time spraying until the skin surface was slightly moistened. At the same time, the family was advised to change the bed sheets frequently and keep the room ventilated.

[0130] Treatment Effect: After five days of treatment, skin redness significantly improved and pain was alleviated. Two weeks after treatment, new skin tissue began to grow at the eroded area, exudation ceased, and the skin was essentially flat again, with only a slight amount of pigmentation remaining. After another week of consolidation treatment, the skin returned to normal, and the skin problems caused by incontinence have not recurred.

[0131] Case 3

[0132] Basic information of the patient: Grandma Wang, 85 years old, suffers from Alzheimer's disease, cannot take care of herself, and has severe incontinence. The skin of her sacrum and coccyx has been irritated by excrement for a long time, resulting in severe incontinence dermatitis. The skin ulcers are large in area and deep into the superficial dermis. There is obvious redness, swelling, fever, and an odor around the skin.

[0133] Treatment process: The nursing team selected Example 3 of the present invention's topical gel for incontinence dermatitis. Daily, the affected skin was rinsed with saline and gently dried. The gel was then evenly applied to the affected skin and surrounding red and swollen areas to a thickness of approximately 2-3 mm. The gel was then covered with sterile gauze and changed twice daily.

[0134] Treatment Results: Within the first three days of treatment, redness and swelling subsided slightly, and the odor lessened. After one week, the amount of exudate from the ulcer decreased significantly, and new granulation tissue began to grow. After three weeks of treatment, the skin ulcer had essentially healed, and the redness and swelling had completely subsided, leaving only a shallow scar. Since then, with intensive care, Grandma Wang's incontinence dermatitis has not recurred, and her skin condition has gradually improved.

[0135] 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 in the scope of protection of the present invention.

Claims

1. A medicament for external use for incontinence dermatitis, characterized in that: The invention is composed of the following raw materials in parts by weight: 20-35 parts of improved grapefruit oil, 10-20 parts of a biodegradable film-forming polymer, 5-10 parts of a composite anti-inflammatory agent, 8-15 parts of an astringent, 5-15 parts of an emulsifier, and 3-10 parts of a moisturizer; the composite anti-inflammatory agent is composed of composite extracts of Torreya grandis, Alpinia oxyphylla, and Lygodium japonicum in a mass ratio of (5-13):(2-10):(1-3); The extraction method of the improved grapefruit oil: (1) Crushing: Take mature, non-deteriorated grapefruit seeds, screen and remove impurities, and crush them to 20-40 mesh; (2) Enzymatic hydrolysis: the crushed grapefruit seeds were mixed with water at a mass volume ratio of grapefruit seeds to water of 25-35:100, the pH value was adjusted to 6-8, and then an enzyme preparation of 2-5% by mass of the grapefruit seeds was added, and enzymatic hydrolysis was performed at 25-30°C for 3-8 hours. The enzyme preparation contained protease, amylase, and pectinase in a mass ratio of 1:1-3:3-5, and the mixture was centrifuged to obtain oil I; (3) Pulsed electric field treatment: The above-mentioned oil I is placed in a pulsed electric field treatment device and treated with a pulsed DC electric field for 20-50 min at a pulse frequency of 2.3-2.7 kHz, a voltage of 10-50 V, a pulse width of 20-50 μs, and a pulse number of 15-30 times to obtain oil II; (4) High-pressure microfluidization treatment: The oil II is subjected to high-pressure microfluidization treatment 2-5 times, each time for 15-25 min, with a treatment pressure of 100-500 MPa and a flow rate of 5-10 mL / min, followed by filtration and centrifugation for purification to obtain improved grapefruit oil; The astringent is a mixture of metal ion chelating agent disodium edetate, gallnut tannin and gallic acid in a mass ratio of (3-7): (8-15): (2-6).

2. The external-use medicament for incontinence dermatitis according to claim 1, characterized in that: The invention is composed of the following raw materials in parts by weight: 28 parts of improved grapefruit oil, 15 parts of biodegradable film-forming polymer, 8 parts of composite anti-inflammatory agent, 12 parts of astringent, 10 parts of emulsifier and 7 parts of moisturizer.

3. The external-use medicament for incontinence dermatitis according to claim 1, wherein: The extraction method of the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata comprises the following steps: selecting high-quality, dry and mildew-free Torreya grandis branches and leaves and dry and plump Alpinia oxyphylla and Lycopodiella ternata branches and leaves, crushing them into 20-30 meshes, soaking and extracting them with water for 3-5 hours, adding an extraction solvent for ultrasonic extraction, wherein the mass volume ratio of the mixed powder and the extraction solvent is 1:8-12, the extraction solvent is anhydrous ethanol, ethyl acetate and water in a volume ratio of 4-6:1-3:20, the ultrasonic frequency is 20-40kHz, the ultrasonic power is 300-500W, the ultrasonic time is 30-60min, and the temperature during ultrasonic extraction is controlled at 40-50°C to obtain the composite extract of Torreya grandis, Alpinia oxyphylla and Lycopodiella ternata.

4. The external-use medicament for incontinence dermatitis according to claim 1, wherein: The biodegradable film-forming polymer comprises polylactic acid-glycolic acid copolymer and trimethylsiloxysilicate in a mass ratio of 1:1-3.

5. The external-use medicament for incontinence dermatitis according to claim 1, characterized in that: The emulsifier is selected from any one or a combination of propylene glycol, glycerin, sodium lauryl sulfate, sodium carboxymethyl cellulose and polysorbate 80.

6. The external-use medicament for incontinence dermatitis according to claim 1, characterized in that: The moisturizing agent is a mixture of sodium hyaluronate and ceramide in a mass ratio of 2:1-2.

7. The method for preparing the external-use medicament for incontinence dermatitis according to claim 1, wherein: The following steps are involved: S1. Ultrafinely pulverize the composite anti-inflammatory agent and the astringent to a particle size of 1-10 μm, and then mix them uniformly to obtain an active mixed powder; S2. Slowly add the modified grapefruit oil to the active mixed powder under ultrasound-assisted conditions at a frequency of 20-40 kHz and continue ultrasonic stirring for 30-60 minutes to allow for full integration; S3. Add a biodegradable film-forming polymer, an emulsifier, and a moisturizer to the above system in sequence, stir for 2-5 hours at a constant temperature of 35-45°C and a stirring speed of 400-600 rpm, until a uniform semi-fluid finished drug product is formed, and then prepare it into a spray form, a gel form, or a cream form to obtain an external-use drug for incontinence dermatitis.

8. The method for preparing the external-use medicament for incontinence dermatitis according to claim 7, wherein: The ultrasonic treatment of S2 was performed using intermittent ultrasonication, with a 2-min pause every 10 min.

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