External medicine for incontinent dermatitis and preparation method thereof

Abstract

The invention provides an external medicine for incontinence dermatitis and a preparation method thereof. The external medicine is prepared from 20-35 parts of improved grapefruit oil, 10-20 parts of biodegradable film-forming polymer, 5-10 parts of composite anti-inflammatory agent, 8-15 parts of astringent, 5-15 parts of emulsifier and 3-10 parts of humectant, wherein the composite anti-inflammatory agent contains a composite extract of cephalotaxus sinensis, fructus alpiniae oxyphyllae and lygodium japonicum according to a specific mass ratio. The improved grapefruit oil is extracted through multiple steps of crushing, enzymolysis, pulsed electric field treatment, high-pressure microjet and the like. The composite anti-inflammatory agent has a specific water immersion ultrasonic extraction mode; all raw material components such as a biodegradable film-forming polymer, an astringent and the like are also definitely formed. The preparation method comprises the steps of raw material treatment, ultrasonic-assisted fusion, addition of other components, stirring and the like, and finally, spray, gel or cream can be prepared. The traditional Chinese medicine composition integrates various natural and functional components, aims to provide an effective external medicine for treating incontinent dermatitis, and is expected to improve skin symptoms of patients and promote skin repair.

Description

Technical Field

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

[0002] Incontinence dermatitis ( Incontinence-Associated Dermatitis IAD is a common skin problem that has long plagued caregivers and patients in clinical practice, especially among the elderly, paralyzed patients, and people with incontinence caused by neurological diseases. In the incontinent state, the skin is exposed to urine, feces and other excretions for a long time. The irritants contained in them will destroy the barrier function of the skin, causing a series of inflammatory reactions such as redness, itching, pain, ulceration and exudation of the skin, which not only brings great pain to patients, but also increases the risk of complications such as infection, seriously affecting the quality of life of patients and the recovery process of the disease.

[0003] At present, topical drugs are often used in the treatment of incontinence dermatitis. The topical drugs for incontinence dermatitis in the prior art mainly have the following deficiencies:

[0004] (1) Drug ingredients and efficacy

[0005] Limited anti-inflammatory effect: Although most existing topical drugs have certain anti-inflammatory effects, their ability to inhibit the production of inflammatory factors and reduce 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 problem of skin exudation 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] The dosage form is limited: Common dosage forms on the market, such as traditional ointments and lotions, have their own disadvantages. Ointments may have a thick texture, which may affect the skin's normal metabolism after application; lotions have a short duration of action and need to be used frequently, which brings inconvenience to nursing work, and have insufficient coverage and protection for skin ulcers, and cannot effectively isolate the continuous stimulation of excrement.

[0010] Poor film-forming property: 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 protective and therapeutic effects of the medication on the skin. Frequent reapplication of the medication 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 the biocompatibility with human skin when selecting raw materials, which may lead to allergies, intolerance and other symptoms after drug use, which is not conducive to long-term use. Especially for diseases such as incontinence dermatitis that require continuous medication, biocompatibility issues should be taken more seriously.

[0014] In view of the above-mentioned deficiencies of existing topical drugs for incontinence dermatitis, there is an urgent need to develop a new topical drug 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 biodegradable film-forming polymer, 5-10 parts of composite anti-inflammatory agent, 8-15 parts of astringent, 5-15 parts of emulsifier, and 3-10 parts of 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 drug for incontinence dermatitis external composite anti-inflammatory agent includes 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.

[0018] Furthermore, the extraction method of the composite extract of Torreya grandis, Alpinia oxyphylla and Lygodium japonica is to select high-quality, dry and mildew-free Torreya grandis branches and leaves and dry and plump Alpinia oxyphylla and Lygodium japonica 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 Lygodium japonica.

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

[0020] (1) Crushing: taking mature, non-deteriorated grapefruit seeds, screening and removing impurities, and crushing them into 20-40 meshes;

[0021] (2) Enzymatic hydrolysis: the crushed grapefruit seeds are mixed with water, the mass volume ratio of grapefruit seeds to water is 25-35:100, the pH value is adjusted to 6-8, and then an enzyme preparation of 2-5% by mass of the grapefruit seeds is added, and enzymatic hydrolysis is performed at 25-30° C. for 3-8 hours. The enzyme preparation is a protease, an amylase, and a pectinase in 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) Pulse electric field treatment: the crude oil is placed in a pulse electric field treatment device, and a pulse direct current electric field is applied for treatment 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 pulse 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: The oil II is subjected to high-pressure microfluidization treatment for 2-5 times, each time for 15-25 minutes, with a treatment pressure of 100-500 MPa and a flow rate of 5-10 mL / min, filtered and centrifuged for purification to obtain improved grapefruit oil. The tiny particles and impurities in the oil are further broken and separated, and this process 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 ethylenediaminetetraacetic acid, gallotannin 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 agent for incontinence dermatitis comprises the following steps:

[0029] S1, respectively subjecting the composite anti-inflammatory agent and the astringent to ultrafine grinding to a particle size of 1-10 μm, and then mixing them evenly to obtain an active mixed powder;

[0030] S2. Slowly add the extracted grapefruit oil to the active mixed powder under ultrasound-assisted conditions at an ultrasound frequency of 20-40 kHz, and continue ultrasonic stirring for 30-60 minutes to fully blend it;

[0031] S3. Add biodegradable film-forming polymer, emulsifier and 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 400-600rpm until a uniform semi-fluid drug product is formed, and then make 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 of S2 is performed intermittently, with a 2-minute pause after every 10-minute 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 invention has the following beneficial effects.

[0034] The composite extracts of Torreya grandis, Alpinia oxyphylla and Lygodium japonicum in a specific mass ratio in the composite anti-inflammatory agent contained in the composite anti-inflammatory agent for incontinence dermatitis of the present invention can synergistically exert excellent anti-inflammatory effects, 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 air permeability 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 to ensure the effectiveness and safety of the drug, and can be made into a variety of dosage forms such as sprays, gels, creams, etc., to meet different usage needs and clinical care scenarios, and improve the convenience of use. In addition, the drug makes full use of a variety of natural plant extracts as the main ingredients, combined with safety-proven excipients, with high safety and good biocompatibility, suitable for long-term use, and provides a comprehensive performance, safe, reliable, convenient and effective solution for the treatment of incontinence dermatitis, with great clinical application value and social benefits. DETAILED DESCRIPTION

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

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

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

[0039] An external-use medicine for incontinence dermatitis comprises the following raw materials in parts by weight: 20 parts of improved grapefruit oil, 10 parts of biodegradable film-forming polymer, 5 parts of composite anti-inflammatory agent, 8 parts of astringent, 5 parts of emulsifier and 3 parts of 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 Lygodium japonicum is as follows: high-quality, dry and mildew-free Torreya grandis branches and leaves, dry and plump Alpinia oxyphylla and Lygodium japonicum 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 20kHz, the ultrasonic power is 300W, the ultrasonic time is 30-60min, and the temperature during ultrasonic extraction is controlled at 40°C to obtain the composite extract of Torreya grandis, Alpinia oxyphylla and Lygodium japonicum.

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

[0044] The emulsifier is selected from propylene glycol.

[0045] The moisturizer 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 meshes;

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

[0049] (3) Pulse electric field treatment: the crude oil was placed in a pulse 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 a pulse number of 15 times 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] An external-use medicine for incontinence dermatitis comprises the following raw materials in parts by weight: 35 parts of improved grapefruit oil, 20 parts of biodegradable film-forming polymer, 10 parts of composite anti-inflammatory agent, 15 parts of astringent, 15 parts of emulsifier and 10 parts of 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 Lygodium japonica is as follows: high-quality, dry and mildew-free Torreya grandis branches and leaves, dry and plump Alpinia oxyphylla and Lygodium japonica 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 Lygodium japonica.

[0055] The astringent is a mixture of metal ion chelating agent disodium ethylenediaminetetraacetate, gallotannin 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: taking mature, non-deteriorated grapefruit seeds, screening and removing impurities, and crushing them into 20-40 meshes;

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

[0061] (3) Pulse electric field treatment: the crude oil was placed in a pulse 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 a pulse number of 30 times to obtain oil II;

[0062] (4) High-pressure microfluidization treatment: The oil II was subjected to high-pressure microfluidization treatment for 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] An external-use medicine for incontinence dermatitis comprises 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.

[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 Lygodium japonicum is as follows: high-quality, dry and mildew-free Torreya grandis branches and leaves, dry and plump Alpinia oxyphylla and Lygodium japonicum 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 Lygodium japonicum.

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

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

[0069] The moisturizer 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 meshes;

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

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

[0074] (4) High-pressure microfluidization treatment: The oil II was subjected to high-pressure microfluidization treatment for 3 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, respectively subjecting the composite anti-inflammatory agent and the astringent to ultrafine grinding to a particle size of 6 μm, and then mixing them uniformly to obtain an active mixed powder;

[0077] S2. Under ultrasound-assisted conditions, the extracted grapefruit oil was slowly added to the active mixed powder at an ultrasonic frequency of 30 kHz, and ultrasonic stirring was continued for 50 minutes to fully blend it;

[0078] S3. Add biodegradable film-forming polymer, emulsifier and moisturizer to the above system in sequence, 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 make 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 medicine for incontinence dermatitis includes the following raw materials in parts by weight: 15 parts of improved 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 medicine 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 medicine 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 medicine for incontinence dermatitis is tannic acid.

[0087] 1. Validity Verification

[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 in wound exudate.

[0090] 2. Dilute the test drug with normal saline to 1 / 4 of the original drug concentration, and 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 an equal volume (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 an equal amount (5 mL) of simulated skin exudate to each test tube, mix thoroughly, and let it stand at room temperature for observation.

[0093] At 15 minutes, 30 minutes, 60 minutes and other time points, the turbidity changes of the solutions in each test tube were observed, and the absorbance value was detected at a specific wavelength (620nm, at which the protein precipitation had a significant change in light absorption). The lower the absorbance value, the clearer the solution, which means that the more protein was precipitated, that is, the better the convergence effect. The data of different concentration drug groups were compared with the positive control group and the blank control group to analyze the convergence ability and effective concentration range of the drug.

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

[0095] 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 convergence effect, causing the protein in the simulated exudate to precipitate and the solution gradually becomes clear.

[0096] Test Example 2-Anti-inflammatory Effect Test

[0097] 1. Establishment of Cellular Inflammation Model and Drug Treatment

[0098] 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 carried out after the cells grew to the logarithmic growth phase.

[0099] Induction of inflammation: cells were plated at a density of 1 × 10 5 / mL) were inoculated in a 96-well plate or culture dish. 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.

[0100] Drug intervention: dilute the test drug to a concentration (10 μg / mL) with serum-free culture medium, add the drug solution of the experimental group to the cells after inflammation induction, and set up a positive control group (dexamethasone) and a blank control group (only add inflammation inducer and culture medium, no drug). Set up multiple replicate wells (such as 6 replicate wells) for each group and continue culturing for 24-48 hours.

[0101] 2. Detection of inflammatory factors

[0102] 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.

[0103] Enzyme-linked immunosorbent assay (ELISA): The ELISA kit was used according to the operating procedures in the instructions to detect the content of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β)) in the supernatant. The absorbance value of each well at the corresponding wavelength was read by an enzyme reader, and the specific concentration of the inflammatory factor was calculated according to the standard curve. The differences in the concentration of inflammatory factors in each drug group were compared with the positive control group and the blank control group. The lower the concentration of inflammatory factors, the stronger the effect of the drug in inhibiting inflammation, so as to evaluate the anti-inflammatory effect of the drug and the effective anti-inflammatory concentration range.

[0104] Table 2: Concentrations of inflammatory factors in cell culture supernatant (unit: pg / mL)

[0105] From the above data, it can be seen that under the induction of lipopolysaccharide, 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.

[0106] After the positive control group used dexamethasone, the concentrations of various inflammatory factors were significantly reduced, indicating that dexamethasone played a strong anti-inflammatory effect in this model and effectively inhibited the inflammatory response.

[0107] Compared with the blank control group, the concentration of each inflammatory factor in the embodiment group showed a gradual downward trend. Although it was slightly higher than the positive control group, it was still significantly lower than the blank control group, indicating that the drugs or treatment methods represented by the embodiments 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 embodiment 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 embodiments have certain anti-inflammatory ability, can intervene in the cellular inflammatory response to a certain extent, and reduce the degree of inflammation.

[0108] Test Example 3-Skin Repair Effect Test

[0109] Cell proliferation experiment (in vitro): Keratinocytes are cultured and treated with drugs. The cell proliferation is detected by cell proliferation detection method (BrdU incorporation method). The number or proportion of BrdU positive cells is detected. The more positive cells there are, the more active the cell proliferation is. This is used to evaluate the potential effect of drugs in promoting skin cell proliferation and thus on skin repair.

[0110] Experimental Grouping

[0111] Blank control group: contains only culture medium without drugs.

[0112] Positive control group: epidermal growth factor, concentration was 10 ng / mL.

[0113] Drug group: concentration was 10 μg / mL.

[0114] Table 3: Proportion of BrdU positive cells in different groups

[0115]

[0116] The proportion of BrdU-positive cells in the blank control group was only 12.5±1.2%, which indicates that in the absence of additional drugs to promote cell proliferation, the cells are in a normal basal proliferation state with relatively low proliferation activity, indicating 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.

[0117] The positive control group used epidermal growth factor (concentration of 10 ng / mL), which is commonly used in clinical practice, and its BrdU positive cell ratio reached 38.2±2.5%, which was significantly higher than that of the blank control group. This shows that epidermal growth factor, as an effective cell proliferation factor, can significantly stimulate skin-related cells in vitro.

[0118] The groups represented by the embodiment group have BrdU positive cell ratios of 36.8±2.0%, 36.5±2.0%, and 37.5±2.2%, respectively, which are all close to the positive control group. This means that the drugs or treatment methods involved in the embodiments 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 skin repair effect and can significantly increase the proliferation activity of cells, which is expected to accelerate the process of skin repair. This shows that the embodiment group has shown advantages comparable to the positive control drug at the in vitro cell level, and it can be inferred that it will have a positive promoting effect on skin repair in practical applications.

[0119] There is a certain gap between the comparative group and the example group and the positive control group. This reflects that the drug or treatment represented by the comparative group is not as effective as 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, indicating that after optimization and adjustment, the example group can better play the role of promoting skin repair.

[0120] 2. Typical Cases

[0121] Case 1

[0122] Patient's basic information: Ms. Zhang, 72 years old, has been bedridden for a long time after a stroke, unable to take care of herself, and has incontinence. During the nursing process, the skin on the buttocks and perineum gradually became red and itchy, followed by small areas of ulceration with obvious exudation. The doctor diagnosed it as incontinence dermatitis.

[0123] Treatment process: The medical staff selected the incontinence dermatitis external-use medicine of Example 3 of the present invention and prepared it into a cream dosage form. After cleaning the patient's skin, apply it to the damaged skin three times a day, apply it gently, and use a breathable nursing pad to keep the skin relatively dry.

[0124] Treatment effect: After one week of medication, the exudate of the skin was significantly reduced, the redness and swelling were reduced, and the patient reported that the itching was relieved; after two weeks of continued use, the ulcer began to gradually scab and heal, and the skin color gradually returned to normal, basically healed. After one month of follow-up observation, there was no recurrence, and the skin condition was healthier than before.

[0125] Case 2

[0126] Basic information of the patient: Mr. Li, 58 years old, suffered spinal cord injury and lower limb paralysis due to a car accident. He needs a long-term indwelling catheter, but still has occasional urine leakage, resulting in incontinence dermatitis on the inner thigh and scrotum, manifested as large areas of skin flushing, accompanied by pain, and signs of erosion in some areas.

[0127] Treatment process: The incontinence dermatitis topical spray medicine of Example 3 of the present invention was used for treatment. The patient's skin was first disinfected and cleaned, and then the medicine was evenly sprayed 10-15 cm away from the skin, 4 times a day, each time spraying until the skin surface was slightly moistened, and at the same time, the family members were advised to change the bed sheets frequently and keep the room ventilated.

[0128] Treatment effect: After 5 days of treatment, the skin flushing phenomenon was significantly improved and the pain was relieved. After 2 weeks of medication, new skin tissue began to grow at the eroded site, exudation stopped, and the skin basically returned to flatness, leaving only a small amount of pigmentation. After 1 week of consolidation treatment, the skin returned to normal, and no skin problems caused by incontinence occurred again.

[0129] Case 3

[0130] 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 enough to reach the superficial dermis. There is obvious redness, swelling, and fever around the skin, as well as an odor.

[0131] Treatment process: The nursing team selected the incontinence dermatitis topical gel medicine of Example 3 of the present invention. Every day, the skin ulcer was washed with normal saline, and after gently drying, the gel was evenly applied to the damaged skin and the surrounding red and swollen areas with a thickness of about 2-3 mm, and covered with sterile gauze, and the dressing was changed twice a day.

[0132] Treatment effect: In the first 3 days of treatment, the redness and swelling were slightly relieved, and the odor was reduced; after 1 week, the amount of exudate at the ulcer site was significantly reduced, and new granulation tissue began to grow; after 3 weeks of continuous treatment, the skin ulcer was basically healed, the redness and swelling completely subsided, and only a shallow scar was left. After that, Grandma Wang was given intensive care, and incontinence dermatitis did not recur, and her skin condition gradually improved.

[0133] 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 principle of the present invention should be included in the protection scope of the present invention.

Claims

1. An external-use medicine for incontinence dermatitis, characterized in that: The invention comprises the following raw materials in parts by weight: 20-35 parts of improved grapefruit oil, 10-20 parts of biodegradable film-forming polymer, 5-10 parts of composite anti-inflammatory agent, 8-15 parts of astringent, 5-15 parts of emulsifier and 3-10 parts of moisturizer; the composite anti-inflammatory agent comprises composite extracts of Torreya grandis, Alpinia oxyphylla and Lygodium japonicum in a mass ratio of (5-13):(2-10):(1-3).

2. The medicament for incontinence dermatitis as claimed in claim 1, characterized in that: The invention comprises 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 medicament for incontinence dermatitis as claimed in claim 1, characterized in that: The method for extracting the composite extract of Torreya grandis, Alpinia oxyphylla and Lygodium japonica comprises the following steps: selecting high-quality, dry and mildew-free Torreya grandis branches and leaves, dry and plump Alpinia oxyphylla and Lygodium japonica 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 Lygodium japonica.

4. The medicament for incontinence dermatitis as claimed in claim 1, characterized in that: The extraction method of the improved grapefruit oil: (1) Crushing: Take mature, non-deteriorated grapefruit seeds, screen and remove impurities, and crush them into 20-40 mesh; (2) Enzymatic hydrolysis: the crushed grapefruit seeds are mixed with water, the mass volume ratio of grapefruit seeds to water is 25-35:100, the pH value is adjusted to 6-8, and then an enzyme preparation of 2-5% by mass of the grapefruit seeds is added, and enzymatic hydrolysis is performed at 25-30° C. for 3-8 hours. The enzyme preparation is a protease, amylase, and pectinase in a mass ratio of 1:1-3:3-5, and centrifugation is performed to obtain oil I; (3) Pulse electric field treatment: the crude oil is placed in a pulse electric field treatment device and treated with a pulsed DC 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 to obtain oil II; (4) High-pressure microfluidization treatment: The oil II is subjected to high-pressure microfluidization treatment for 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, filtered and centrifuged for purification to obtain improved grapefruit oil.

5. The medicament for incontinence dermatitis as claimed in claim 1, characterized in that: The biodegradable film-forming polymer comprises polylactic acid-glycolic acid copolymer and trimethylsiloxysilicate in a mass ratio of 1:1-3.

6. The medicament for incontinence dermatitis as claimed in claim 1, characterized in that: The astringent is a mixture of metal ion chelating agent disodium ethylenediaminetetraacetate, gallotannin and gallic acid in a mass ratio of (3-7):(8-15):(2-6).

7. The medicament for incontinence dermatitis as claimed in 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.

8. The medicament for incontinence dermatitis as claimed in claim 1, characterized in that: The moisturizing agent is a mixture of sodium hyaluronate and ceramide in a mass ratio of 2:1-2.

9. The method for preparing a compound anti-inflammatory agent for incontinence dermatitis according to claim 1, characterized in that: The following steps are involved: S1, respectively subjecting the composite anti-inflammatory agent and the astringent to ultrafine grinding to a particle size of 1-10 μm, and then mixing them evenly to obtain an active mixed powder; S2. Slowly add the extracted grapefruit oil to the active mixed powder under ultrasound-assisted conditions at an ultrasound frequency of 20-40 kHz, and continue ultrasonic stirring for 30-60 minutes to fully blend it; S3. Add biodegradable film-forming polymer, emulsifier and 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 400-600rpm until a uniform semi-fluid drug product is formed, and then make it into a spray form, a gel form or a cream form to obtain an external-use drug for incontinence dermatitis.

10. The method for preparing a compound anti-inflammatory drug for incontinence dermatitis according to claim 8, characterized in that: The ultrasonic treatment of S2 was performed using intermittent ultrasonic treatment, with a 2-min pause after every 10-min ultrasonic treatment.

Images