Externally applied medicine for incontinent dermatitis and preparation method thereof

Abstract

The invention provides an external application medicine for incontinent dermatitis and a preparation method thereof. The composition is prepared from active ingredients such as a radix sophorae flavescentis extract, calamine, vitamin E, ceramide, a herba portulacae extract, glycyrrhizic acid, chitosan and colloidal oat powder according to a specific proportion. Moisturizing matrixes such as sodium hyaluronate and glycerol and functional components such as tea tree essential oil are supplemented. And through a preparation process of matching high-speed shearing with ultrasonic dispersion, uniform dispersion and stability of each component are ensured. Experimental results show that the composition shows a remarkable synergistic effect in the aspects of anti-inflammation, antibiosis, skin barrier repair and the like, the comprehensive relieving and repairing effect of the composition is superior to that of a conventional drug control, and all the components and a special preparation process are necessary for achieving the optimal effect. The product has no irritation to human skin, is good in safety, can be prepared into various dosage forms such as cream, hydrogel or spray, and is suitable for nursing and repairing sensitive skin.

Description

Technical Field

[0001] This invention relates to the field of biomedical preparation technology, and in particular to a topical medicine for incontinence-related dermatitis and its preparation method. Background Technology

[0002] Incontinence-related dermatitis is an inflammatory reaction caused by long-term irritation of the skin by excretions such as urine and feces, leading to damage to the skin barrier. It is common in patients who are bedridden for a long time, the elderly, and people with disabilities. Clinical manifestations include skin erythema, papules, erosion, and exudation. In severe cases, ulcers may occur, accompanied by itching and pain, which seriously affects the patient's quality of life.

[0003] Currently, commonly used topical medications for incontinence-related dermatitis mainly include simple moisturizers, antibacterial ointments, and corticosteroids, but they have several shortcomings: First, their efficacy is limited; most medications only focus on anti-inflammation or moisturizing, lacking coverage of the entire course of the disease ("anti-inflammation-antibacterial-repair-healing"), making it difficult to simultaneously address skin barrier repair and wound healing. Second, their components have poor synergy; most are simple mixtures without targeted synergistic effects, resulting in slow onset and frequent recurrences in severe erosive exudative dermatitis. Third, some medications are highly irritating, especially those containing high concentrations of chemical components, which can easily aggravate discomfort in damaged skin. Fourth, their formulation adaptability is insufficient; a single formulation cannot meet the needs of different scenarios, such as areas inconvenient for bedridden patients to apply to, or wounds with significant exudation. Fifth, existing medications have poor adaptability to similar skin problems such as eczema of the buttocks and intertrigo, failing to form a treatment plan covering multiple conditions.

[0004] Therefore, developing a topical medication with synergistic ingredients, gentle and non-irritating properties, flexible dosage form, that combines prevention and treatment, and is suitable for a variety of related skin problems has become a pressing technical problem to be solved in clinical practice. Summary of the Invention

[0005] In view of this, the present invention proposes a topical medicine for incontinence-related dermatitis and a preparation method thereof, thereby solving the above problems.

[0006] The technical solution of the present invention is implemented as follows: it is composed of active ingredients and pharmaceutically acceptable excipients. The active ingredients include the following raw materials in parts by weight: 5-15 parts of Sophora flavescens extract, 10-20 parts of calamine, 3-8 parts of vitamin E, 1-5 parts of ceramide, 3-10 parts of Portulaca oleracea extract, 2-4 parts of glycyrrhetinic acid, 2-6 parts of chitosan, and 1-3 parts of colloidal oat flour.

[0007] Preferably, the active ingredient comprises the following raw materials in parts by weight: 10 parts Sophora flavescens extract, 15 parts calamine, 5 parts vitamin E, 3 parts ceramide, 8 parts purslane extract, and 4 parts chitosan.

[0008] Preferably, the Sophora flavescens extract is obtained by refluxing Sophora flavescens with 70-80% v / v ethanol to obtain total flavonoids with a purity ≥85%; the Portulaca oleracea extract is prepared by water extraction and alcohol precipitation of the whole Portulaca oleracea herb, wherein the content of flavonoid compounds is ≥12%.

[0009] Preferably, the colloidal oat powder is prepared by the following method: hulled pure natural oats are selected, washed, dried, and roasted at 100-120℃ for 15-30 minutes. The roasted oats are placed in an ultra-micro pulverizer and pulverized under low-temperature circulating water cooling conditions until more than 95% of the particles reach a particle size of less than 10 micrometers. Then, the powder of the target particle size is collected by airflow classification. The obtained oat powder is sterilized at low temperature by cobalt-60 irradiation with an irradiation dose of 4-8 kGy, and then vacuum-sealed in a sterile environment.

[0010] Preferably, the pharmaceutically acceptable excipients include a humectant, a penetration enhancer, and a soothing agent, wherein the humectant is a compound of sodium hyaluronate and glycerin at 0.8-1.5 parts by weight, the penetration enhancer is 2-5 parts by weight, and the soothing agent is tea tree oil at 0.5-2 parts by weight.

[0011] Preferably, the weight ratio of sodium hyaluronate to glycerin is 1:2-3.

[0012] Preferably, the penetration enhancer is selected from any one of laurocapram, menthol, limonene, or oleic acid.

[0013] Preferably, a method for preparing a topical medication for incontinence-related dermatitis includes the following steps:

[0014] S1. Raw material pretreatment: Take Sophora flavescens extract and Portulaca oleracea extract for later use; add chitosan to 1% v / v acetic acid solution and stir at 30-35℃ until completely dissolved to prepare chitosan solution; take colloidal oat flour and pre-disperse it with 20-40% glycerol by weight of oat flour until there are no agglomerated particles to obtain oat flour dispersion.

[0015] S2. Preparation of excipient matrix: Sodium hyaluronate and glycerin are mixed in the above proportion, tea tree oil is added, and the mixture is stirred at 40-45℃ for 10-15 minutes until uniform. Then, a penetration enhancer is added, and the mixture is stirred for another 5-8 minutes to form the excipient matrix.

[0016] S3. Mixing and Blending: Add Sophora flavescens extract, vitamin E, ceramide, and glycyrrhetinic acid to the excipient matrix in sequence, and stir at 500-600 r / min for 8-15 min; then add calamine powder, purslane extract, and the chitosan solution and oat flour dispersion prepared in S1, heat to 45-50℃, and stir at 800-1000 r / min for 15-20 min. During this period, ultrasonically disperse the mixture for 30 s every 5 min at a power of 200-300 W to ensure uniform dispersion of the materials.

[0017] S4. Homogenization and sterilization: Place the mixture into a high-pressure homogenizer and homogenize it 2-3 times at a pressure of 20-30MPa. Then sterilize it at 105-115℃ for 18-22 minutes. After cooling to room temperature, fill it into cream, hydrogel or spray form.

[0018] Preferably, the dosage form of the topical medication is a cream, hydrogel, or spray.

[0019] Preferably, the use of a topical medication for incontinence dermatitis in the preparation of a medicament for the prevention and / or treatment of incontinence dermatitis, eczema of the buttocks, or intertrigo.

[0020] Compared with the prior art, the beneficial effects of the present invention are:

[0021] This invention overcomes the limitations of existing drugs, which suffer from single efficacy and insufficient synergy, by precisely combining active ingredients to form a multi-dimensional synergistic system. The "anti-inflammatory triplet" composed of Sophora flavescens extract, Portulaca oleracea extract, and glycyrrhetinic acid can effectively inhibit the release of inflammatory factors such as TNF-α and IL-6. The β-glucan in colloidal oat flour, along with ceramides and chitosan, forms a barrier repair combination, accelerating the repair of the stratum corneum.

[0022] This invention designs a customized preparation process for different components, avoiding common industry problems such as component agglomeration and activity loss from the source, providing a core guarantee for stable efficacy. In the raw material pretreatment stage, chitosan is dissolved in acetic acid solution and colloidal oat flour is pre-dispersed with glycerol to avoid clumping during subsequent mixing; in the mixing and blending stage, staged temperature-controlled stirring and intermittent ultrasonic dispersion, combined with high-pressure homogenization, ensure uniform particle size of materials; while ensuring the sterility of the drug, the inactivation of active ingredients such as total flavonoids of Sophora flavescens and vitamin E is avoided, further ensuring the stability of efficacy within the drug's shelf life.

[0023] The selected natural high-purity extracts, combined with tea tree oil, are non-irritating to the skin. The medication is suitable for the treatment of severe wounds and can also be used for daily protection of patients who are bedridden for a long time. Detailed Implementation

[0024] To better understand the technical content of this invention, specific embodiments are provided below to further illustrate the invention.

[0025] Unless otherwise specified, the experimental methods used in the embodiments of this invention are all conventional methods.

[0026] Unless otherwise specified, all materials and reagents used in the embodiments of this invention are commercially available.

[0027] Example 1

[0028] 1. Active ingredients by weight: 5 parts Sophora flavescens extract, 10 parts calamine, 3 parts vitamin E, 1 part ceramide, 3 parts purslane extract, 2 parts glycyrrhetinic acid, 2 parts chitosan, 1 part colloidal oat flour;

[0029] 2. Moisturizer 0.8 parts (sodium hyaluronate and glycerin compound ratio 1:2), tea tree oil 0.5 parts, laurocapram 2 parts;

[0030] 3. The Sophora flavescens extract is obtained by refluxing Sophora flavescens with 75% v / v ethanol to obtain total flavonoids with a purity ≥85%; the Portulaca oleracea extract is prepared by water extraction and alcohol precipitation of the whole Portulaca oleracea herb, wherein the content of flavonoid compounds is ≥12%.

[0031] 4. Colloidal oat flour is prepared by the following method: hulled pure natural oats are selected, washed, dried, and roasted at 110℃ for 20 minutes. The roasted oats are placed in an ultra-fine pulverizer and pulverized under low-temperature circulating water cooling conditions until more than 95% of the particles reach a particle size of less than 10 micrometers. Then, the powder of the target particle size is collected by airflow classification. The obtained oat flour is sterilized at low temperature by cobalt-60 irradiation with an irradiation dose of 6 kGy, and then vacuum-sealed in a sterile environment.

[0032] Example 2

[0033] 1. Active ingredients by weight: 15 parts Sophora flavescens extract, 20 parts calamine, 8 parts vitamin E, 5 parts ceramide, 10 parts purslane extract, 4 parts glycyrrhetinic acid, 6 parts chitosan, and 3 parts colloidal oat flour;

[0034] 2. Moisturizer 1.5 parts (sodium hyaluronate and glycerin compound ratio 1:2), tea tree oil 2 parts, laurocapram 5 parts.

[0035] The Sophora flavescens extract and colloidal oat flour were prepared using the method described in Example 1.

[0036] Example 3

[0037] 1. Active ingredients by weight: 10 parts Sophora flavescens extract, 15 parts calamine, 5 parts vitamin E, 3 parts ceramide, 8 parts purslane extract, and 4 parts chitosan;

[0038] 2. Excipients: 1 part moisturizer (sodium hyaluronate and glycerin compounded in a 1:2 ratio), 1 part tea tree oil, and 3 parts menthol.

[0039] The Sophora flavescens extract and colloidal oat flour were prepared using the method described in Example 1.

[0040] The above Examples 1-3 adopted the following preparation steps:

[0041] S1. Raw material pretreatment: Take Sophora flavescens extract and Portulaca oleracea extract for later use; add chitosan to 1% v / v acetic acid solution and stir at 32℃ until completely dissolved to prepare chitosan solution; take colloidal oat flour and pre-disperse it with 20-40% glycerol by weight of oat flour until there are no agglomerated particles to obtain oat flour dispersion.

[0042] S2. Preparation of excipient matrix: Sodium hyaluronate and glycerin are mixed in the above proportion, tea tree oil is added, and the mixture is stirred at 42°C for 12 minutes until homogeneous. Then, a penetration enhancer is added, and the mixture is stirred for another 7 minutes to form the excipient matrix.

[0043] S3. Mixing and blending: Add Sophora flavescens extract, vitamin E, ceramide, and glycyrrhetinic acid to the excipient matrix in sequence and stir at 550 r / min for 12 min; then add calamine powder, purslane extract, chitosan solution prepared in S1, and oat flour dispersion, heat to 48℃, stir at 900 r / min for 18 min, and ultrasonically disperse at 250W for 30 s every 5 min to ensure uniform dispersion of materials;

[0044] S4. Homogenization and sterilization: Place the mixture into a high-pressure homogenizer and homogenize it three times at a pressure of 25 MPa. Then sterilize it at 110°C for 20 minutes. After cooling to room temperature, fill it into cream, hydrogel or spray form.

[0045] Comparative Example 1

[0046] The difference between this comparative example and Example 3 is that glycyrrhetinic acid is missing, while the other components and preparation methods are the same as in Example 3.

[0047] Comparative Example 2

[0048] The difference between this comparative example and Example 3 is that colloidal oat flour is missing; the other ingredients and preparation methods are the same as in Example 3.

[0049] Example 3

[0050] The difference between this comparative example and Example 3 is that the Sophora flavescens extract is replaced with an equal amount of Scutellaria baicalensis extract, while the other components and preparation methods are the same as in Example 3.

[0051] Comparative Example 4

[0052] The difference between this comparative example and Example 3 is that the purslane extract is replaced with an equal amount of honeysuckle extract, while the other components and preparation methods are the same as in Example 3.

[0053] Comparative Example 5

[0054] The difference between this comparative example and Example 3 is that the high-speed shearing and ultrasonic dispersion steps are omitted in the preparation method; only conventional mechanical stirring (stirring at 400 rpm for 30 minutes) is used for mixing. Drug efficacy testing.

[0055] I. Test Materials and Methods

[0056] (a) Test subjects

[0057] Sixty SPF-grade SD rats (half male and half female, weighing 200-250g) were selected to establish an incontinence-related dermatitis model using a combination of urine immersion and mechanical friction. Successful model establishment was defined as the appearance of obvious erythema and mild erosion on the rat's buttocks, a transepidermal water loss (TEWL) ≥25g / (h・cm²), and an inflammatory factor TNF-α level more than 50% higher than normal skin. The successfully modeled rats were randomly divided into 11 groups of 5 rats each, corresponding to Examples 1-3 and Comparative Examples 1-5, respectively. A blank control group (treated with only physiological saline) and a positive control group (treated with a commonly used incontinence-related dermatitis care ointment containing zinc oxide) were also included.

[0058] (ii) Test Samples

[0059] Examples 1-3 and Comparative Examples 1-5 included cream-based drugs, physiological saline, and a positive control ointment. All samples were tested within one week of preparation and stored at 25°C, sealed and protected from light.

[0060] (III) Testing Methods

[0061] 1. Administration method: Once daily, the corresponding sample was evenly applied to the affected area of ​​rats, with a thickness of 0.2 mm. The blank control group was treated with an equal amount of physiological saline. The administration was continued for 14 days.

[0062] 2. Detection indicators and time points: The following indicators were detected on the 3rd, 7th and 14th days of administration, and the time for complete wound healing was recorded. Skin irritation reaction was observed after administration.

[0063] Anti-inflammatory indicators: The levels of inflammatory factors TNF-α and IL-6 in the affected skin tissue were detected by enzyme-linked immunosorbent assay (ELISA).

[0064] Skin barrier repair indicators: Transepidermal water loss (TEWL) value was measured using a transepidermal water loss analyzer, and stratum corneum moisture content was measured using a skin moisture analyzer.

[0065] Wound healing index: Calculate the wound contraction rate.

[0066] Wound shrinkage rate = (initial wound area - wound area at test) / initial wound area × 100%.

[0067] Record the time it takes for the wound to heal completely (the time it takes for the wound to completely scab over and stop oozing).

[0068] Safety indicators: Refer to the skin irritation rating standard to score the erythema and edema at the application site. The score range is 0-4 points, where 0 points is no irritation and 4 points is severe irritation.

[0069] II. Test Results

[0070] (a) Results of anti-inflammatory effect test

[0071]

[0072]

[0073] (II) Results of Skin Barrier Repair Effect Test

[0074]

[0075]

[0076] (III) Results of wound healing effect test

[0077]

[0078] III. Results Analysis and Conclusions

[0079] (I) Results Analysis

[0080] Anti-inflammatory effects: Examples 1-3 showed significantly better inhibitory effects on TNF-α and IL-6 than all comparative examples and the positive control group. Comparative example 1, lacking glycyrrhetinic acid, had its anti-inflammatory triplet effect disrupted, resulting in a slower decrease in inflammatory factors. Comparative examples 3 and 4, after replacing the core extract, consistently showed higher levels of inflammatory factors than Example 3, indicating that the synergistic anti-inflammatory effects of Sophora flavescens extract, Portulaca oleracea extract, and other components cannot be replaced by Scutellaria baicalensis extract or Lonicera japonica extract. Comparative example 5, due to simplified processing leading to uneven component dispersion, also exhibited lower anti-inflammatory efficiency than Example 3.

[0081] Skin barrier repair effect: The TEWL values ​​of Examples 1-3 decreased more rapidly, and the stratum corneum moisture content increased more significantly. In Comparative Example 2, the skin barrier repair speed was significantly slower after the absence of colloidal oat powder, confirming the synergistic repair effect of β-glucan, ceramide, and chitosan in the colloidal oat powder; the barrier repair effects of the other comparative examples were weaker than those of the examples, further demonstrating the rationality of the original ingredient combination and process.

[0082] Wound healing effect: The wound in Example 2 healed the fastest, completely healing in about 10 days. Examples 1 and 3 were also faster than the comparative examples and the positive control group. Comparative examples 1-4 had low wound contraction rates and prolonged healing times due to insufficient component compatibility. Comparative example 5 had a healing time that was more than 3 days longer than Example 3 due to component aggregation, which hindered the drug's effectiveness.

[0083] The overall stimulation score for both the example and the comparative example was 0, indicating no skin irritation.

[0084] The topical medications in Examples 1-3 of this invention achieve synergistic effects of anti-inflammation, skin barrier repair, and wound healing through specific combinations of active ingredients and optimized preparation processes, and are gentle and non-irritating.

[0085] 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 topical medication for incontinence-related dermatitis, characterized in that, It is composed of active ingredients and pharmaceutically acceptable excipients. The active ingredients include the following raw materials in parts by weight: 5-15 parts Sophora flavescens extract, 10-20 parts calamine, 3-8 parts vitamin E, 1-5 parts ceramide, 3-10 parts Portulaca oleracea extract, 2-4 parts glycyrrhetinic acid, 2-6 parts chitosan, and 1-3 parts colloidal oat flour.

2. The topical medication for incontinence-related dermatitis as described in claim 1, characterized in that, The active ingredients comprise the following raw materials in parts by weight: 10 parts Sophora flavescens extract, 15 parts calamine, 5 parts vitamin E, 3 parts ceramide, 8 parts purslane extract, and 4 parts chitosan.

3. The topical medication for incontinence-related dermatitis as described in claim 1, characterized in that, The Sophora flavescens extract is obtained by refluxing Sophora flavescens with 70-80% v / v ethanol to obtain total flavonoids with a purity ≥85%; the Portulaca oleracea extract is prepared by water extraction and alcohol precipitation of the whole Portulaca oleracea herb, wherein the content of flavonoid compounds is ≥12%.

4. A topical medication for incontinence-related dermatitis as described in claim 1, characterized in that, The colloidal oat powder is prepared by the following method: hulled pure natural oats are selected, washed, dried, and roasted at 100-120℃ for 15-30 minutes. The roasted oats are placed in an ultra-micro pulverizer and pulverized under low-temperature circulating water cooling conditions until more than 95% of the particles reach a particle size of less than 10 micrometers. Then, the powder of the target particle size is collected by airflow classification. The obtained oat powder is sterilized at low temperature by cobalt-60 irradiation with an irradiation dose of 4-8 kGy, and then vacuum-sealed in a sterile environment.

5. A topical medication for incontinence-related dermatitis as described in claim 1, characterized in that, The pharmaceutically acceptable excipients include humectants, penetration enhancers, and soothing agents, wherein the humectant is a compound of sodium hyaluronate and glycerin at 0.8-1.5 parts by weight, the penetration enhancer is 2-5 parts, and the soothing agent is tea tree oil at 0.5-2 parts by weight.

6. A topical medication for incontinence-related dermatitis as described in claim 5, characterized in that, The weight ratio of sodium hyaluronate to glycerin is 1:2-3.

7. A topical medication for incontinence-related dermatitis as described in claim 5, characterized in that, The penetration enhancer is selected from any one of laurocapram, menthol, limonene, or oleic acid.

8. A method for preparing a topical medicament for incontinence-related dermatitis as described in any one of claims 1-7, characterized in that, Includes the following steps: S1. Raw material pretreatment: Take Sophora flavescens extract and Portulaca oleracea extract for later use; add chitosan to 1% v / v acetic acid solution and stir at 30-35℃ until completely dissolved to prepare chitosan solution; take colloidal oat flour and pre-disperse it with 20-40% glycerol by weight of oat flour until there are no agglomerated particles to obtain oat flour dispersion. S2. Preparation of excipient matrix: Sodium hyaluronate and glycerin are mixed in the above proportion, tea tree oil is added, and the mixture is stirred at 40-45℃ for 10-15 minutes until uniform. Then, a penetration enhancer is added, and the mixture is stirred for another 5-8 minutes to form the excipient matrix. S3. Mixing and Blending: Add Sophora flavescens extract, vitamin E, ceramide, and glycyrrhetinic acid to the excipient matrix in sequence, and stir at 500-600 r / min for 8-15 min; then add calamine powder, purslane extract, and the chitosan solution and oat flour dispersion prepared in S1, heat to 45-50℃, and stir at 800-1000 r / min for 15-20 min. During this period, ultrasonically disperse the mixture for 30 s every 5 min at a power of 200-300 W to ensure uniform dispersion of the materials. S4. Homogenization and sterilization: Place the mixture into a high-pressure homogenizer and homogenize it 2-3 times at a pressure of 20-30MPa. Then sterilize it at 105-115℃ for 18-22 minutes. After cooling to room temperature, fill it into cream, hydrogel or spray form.

9. A topical medication for incontinence-related dermatitis as described in any one of claims 1-7, characterized in that, The dosage form of the topical medication is cream, hydrogel, or spray.

10. Use of the topical remedy for incontinence dermatitis as described in claim 9 in the preparation of remedies for the prevention and / or treatment of incontinence dermatitis, eczema of the buttocks, or intertrigo.

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