A mask for targeting skin rash and a preparation method thereof

Abstract

The present application provides a kind of mask for targeting drug skin rash and its preparation method, the mask includes mask substrate and loaded essence, and the active ingredient of essence includes anti-inflammatory component, ceramide mixture, plant extract compound and humectant.The anti-inflammatory component is compounded by astragalus seed extract and acetyl tetrapeptide-15 according to a certain proportion, the ceramide mixture is composed according to a certain proportion, and the plant extract compound contains cortex phellodendri, artemisia annua and the like.In preparation, astragalus seed is extracted by ultrasonic-assisted ethanol, and after vacuum concentration, it is compounded with other components.The mask can significantly reduce skin rash grading, improve stratum corneum water content, inhibit IL-6 and TNF-α, no adverse reaction incidence, with strong anti-inflammatory and barrier repair function, and the safety is superior to existing products.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical skincare preparation technology, and in particular to a facial mask for targeted drug-induced rashes and its preparation method. Background Technology

[0002] Targeted therapies, as an important means of precision cancer treatment, have demonstrated significant efficacy in clinical applications. However, the accompanying skin adverse reactions have become a key issue affecting patients' quality of life and treatment adherence. Clinical data shows that approximately 60%-85% of patients receiving targeted therapy (such as the epidermal growth factor receptor inhibitor EGFR) experience varying degrees of skin toxicity. Among these, acne-like rashes, dryness and itching, and skin barrier damage are the most common. In severe cases, grade II-III rashes may develop, manifesting as erythematous pustules, desquamation, and intense itching on the face, chest, and back, and may even lead to discontinuation of anti-tumor treatment due to intolerance.

[0003] Current clinical management protocols have significant limitations: while traditional topical corticosteroids can provide short-term anti-inflammatory effects, long-term use can further damage the skin barrier; moisturizers can only relieve mild dryness and have limited effectiveness in treating moderate to severe inflammation and barrier repair; oral antihistamines cannot specifically improve the high expression of inflammatory factors such as IL-6 and TNF-α and the abnormal differentiation of keratinocytes induced by targeted drugs. Therefore, developing local intervention products with both potent anti-inflammatory and barrier repair effects and high safety is of great significance in addressing the clinical challenges of targeted drug-induced rashes. Summary of the Invention

[0004] In view of this, the present invention proposes a facial mask for targeted drug-induced rashes and a method for preparing the same, thereby solving the above problems.

[0005] The technical solution of the present invention is implemented as follows: a mask for targeted drug-induced rashes, comprising a mask substrate and an essence loaded on the mask substrate, wherein the active ingredients of the essence comprise the following components by weight percentage: 0.01-0.1% anti-inflammatory component, 0.5-2% ceramide mixture, 1-5% plant extract complex, 5-10% moisturizer, and the balance being solvent.

[0006] Preferably, the anti-inflammatory component comprises Salvia splendens seed extract, and the weight ratio of Salvia splendens to acetyl tetrapeptide-15 is (0.4-1.0):1.

[0007] Preferably, the *Spina coccinea* seed extract is prepared by crushing *Spina coccinea* seeds, passing them through a 40-60 mesh sieve to obtain coarse powder, mixing the coarse powder with an ethanol aqueous solution of 50-70% v / v at a material-to-liquid ratio of 1:8-12, and performing ultrasonic-assisted extraction 1-3 times at 50-65℃, each time for 30-60 minutes; the ultrasonic power is 200-400W. The extracts are combined, filtered, and the filtrate is concentrated under reduced pressure at 50-60℃ and -0.08 to -0.10 MPa until no alcohol odor is detected, to obtain *Spina coccinea* seed extract paste, which is then freeze-dried and crushed to obtain the *Spina coccinea* seed extract.

[0008] Preferably, the ceramide mixture is composed of ceramide 3, ceramide 6II, and ceramide 1 mixed in a weight ratio of (2-4):(1-3):1, and the ceramide is a plant-derived synthetic ceramide with a purity ≥95%.

[0009] Preferably, the plant extract complex is a mixed extract complex of Phellodendron bark, Artemisia annua, Sophora flavescens, and Sanguisorba officinalis.

[0010] Preferably, the moisturizer is composed of sodium hyaluronate, betaine, and sodium polyglutamate mixed in a weight ratio of (1-3):(2-4):1, wherein the molecular weight of sodium hyaluronate is 800-1500 kDa.

[0011] Preferably, the solvent is a mixed solvent composed of deionized water, propylene glycol and glycerol in a mass ratio of (4-6):(2-4):2.

[0012] Preferably, the essence further contains skin microecological regulating components, namely α-glucan oligosaccharides and / or inulin, which are used to promote the colonization of beneficial bacteria in the skin.

[0013] This invention also provides a method for preparing a facial mask for targeted drug-induced rashes, comprising the following steps:

[0014] S1. Preparation of plant extract complex: Phellodendron bark, Artemisia annua, Sophora flavescens and Sanguisorba officinalis are mixed in a weight ratio of (1-3):(2-5):(4-9):1, pulverized to 100-200 mesh, and 5-10 times the weight of 30-50% (v / v) ethanol aqueous solution is added. The mixture is ultrasonically extracted 1-3 times at 35-45℃ and 100-150W for 30-60 minutes each time. The extracts are combined, filtered through a ceramic membrane, and vacuum concentrated until there is no alcohol odor to obtain plant extract concentrate.

[0015] S2. Add the ceramide mixture to glycerin and stir to dissolve at 60-70℃ and 300-500r / min. After cooling to 30-40℃, add the anti-inflammatory peptide and plant extract concentrate and stir at 100-200r / min for 15-30 minutes to obtain the active ingredient dispersion.

[0016] S3. Preparation of the serum: Add the moisturizer and solvent to the active ingredient dispersion in sequence, stir until completely dissolved, adjust the pH to 5.5-6.5, and then filter through a 0.22μm polyethersulfone filter membrane for sterilization;

[0017] S4. Mask Forming: The sterile essence is combined with the pre-treated mask substrate and soaked for 2-4 hours to make the essence load reach 200-300% of the weight of the substrate. Then it is packaged.

[0018] Preferably, in step S1, the pore size of the ceramic membrane is 50-100 nm, the vacuum concentration temperature is 40-50 °C, and the vacuum degree is -0.08 to -0.09 MPa.

[0019] The mask substrate is a nano-biocellulose substrate. The nanofiber is a composite of hyaluronic acid and polyvinyl alcohol. The fiber diameter is 100-500 nanometers, the porosity is 80-90%, and the thickness is 0.1-0.3 mm. The substrate surface is pretreated with plasma with a power of 50-80W for 3-5 minutes.

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

[0021] This invention targets the core pathological mechanisms of targeted drug-induced rashes, namely "high expression of inflammatory factors, skin barrier damage, and microecological imbalance." Through innovative formulation, optimized substrates, and upgraded processes, it achieves a closed-loop intervention of anti-inflammation, repair, and recurrence prevention. Specifically, the synergistic effect of *Tradescantia scabra* seed extract and acetyl tetrapeptide-15, along with a specific ratio of ceramides to repair the skin barrier, demonstrates scientific compatibility. In vitro experiments show that it inhibits the key inflammatory factors IL-6 and TNF-α by 82.5% and 79.6%, respectively, and significantly promotes keratinocyte scratch healing and tight junction protein expression. The synergistic effect of plant extracts and moisturizers overcomes the limitations of simple moisturizers that only alleviate mild dryness, enhancing the integrity of the skin barrier. Clinical evaluation showed no adverse reactions, avoiding the barrier damage risks caused by glucocorticoids, and its safety is superior to existing topical drugs and skincare products.

[0022] Secondly, innovations in formulation technology and dosage form have improved efficacy. The use of ultrasound-assisted ethanol extraction and vacuum concentration technology has improved the extraction efficiency and purity of active ingredients. The process is stable and controllable, making it suitable for large-scale production. Furthermore, the nano-biocellulose substrate, after plasma treatment, has high loading capacity and excellent skin adhesion, promoting the penetration and sustained release of active ingredients. Detailed Implementation

[0023] To better understand the technical content of this invention, specific embodiments are provided below to further illustrate the invention.

[0024] Unless otherwise specified, the experimental methods used in the embodiments of this invention are all conventional methods.

[0025] Unless otherwise specified, all materials and reagents used in the embodiments of this invention are commercially available.

[0026] Example 1 - Preparation of Peppermint Root Seed Extract

[0027] Take 100g of dried *Spiraea japonica* seeds and pulverize them through a 50-mesh sieve. Mix the resulting coarse powder with a 65% v / v ethanol aqueous solution at a material-to-liquid ratio of 1:10. Perform ultrasonic-assisted extraction twice at 60℃ and 300W, 45 minutes each time. Combine the two extracts, coarsely filter through a filter cloth, and then finely filter through a 0.45μm microporous membrane. Concentrate the filtrate under reduced pressure at 55℃ and -0.09MPa until no alcohol odor remains, obtaining an extract. Freeze-dry the extract, pulverize it, and pass it through a 100-mesh sieve to obtain a pale yellow powdery *Spiraea japonica* seed extract for later use.

[0028] Example 2 - Preparation of concentrated plant extract complex

[0029] Weigh out Phellodendron bark, Artemisia annua, Sophora flavescens, and Sanguisorba officinalis according to the specified weight ratio, mix them, and pulverize them to 150 mesh. Add 8 times the weight of 40% v / v ethanol aqueous solution to the herb mixture, and extract twice by ultrasonication at 40℃ and 120W power, 50 minutes each time. Combine the extracts and filter them through a ceramic membrane with a pore size of 80nm to remove macromolecular impurities. Concentrate the filtrate under vacuum at 45℃ and -0.085MPa to a relative density of 1.10 (measured at 50℃) to obtain a concentrated plant extract complex solution for later use.

[0030] Example 3 - Preparation of Facial Mask Essence

[0031]

[0032] Preparation process:

[0033] 1. Add the ceramide mixture to the prescribed amount of glycerol and stir at 65°C and 400 rpm until completely dissolved.

[0034] 2. After cooling to 35°C, add the root extract of Salvia splendens, acetyl tetrapeptide-15 and the concentrated plant extract complex obtained in Example 2, and stir at 150 r / min for 20 minutes to obtain a uniform dispersion of active ingredients.

[0035] 3. In another container, add sodium hyaluronate, betaine, sodium polyglutamate, α-glucan oligosaccharide and solvent to the active ingredient dispersion in sequence, and stir until completely dissolved.

[0036] 4. Adjust the pH to 5.8 with citric acid, and then filter and sterilize using a 0.22μm polyethersulfone (PES) filter membrane to obtain a sterile essence.

[0037] Example 4: Forming of the face mask

[0038] 1. Substrate Pretreatment: A hyaluronic acid / polyvinyl alcohol nanofiber membrane (weight ratio 1:3) with a thickness of 0.2 mm and a porosity of 85% was selected as the substrate. It was placed in a plasma treatment device and treated at 65W power for 4 minutes to increase the surface hydrophilicity.

[0039] 2. Loading with essence: Under sterile conditions, the sterile essence prepared in Example 3 was evenly sprayed onto the pretreated nanofiber membrane, and then soaked in an environment of 20-25°C for 3 hours to make the essence loading reach 250% of the dry weight of the substrate.

[0040] 3. Packaging: Take out the fully loaded mask, put it into an aluminum foil bag, fill it with nitrogen and then heat-seal it to obtain the finished mask for targeted drug rash as described in this invention.

[0041] Comparative Example 1

[0042] The difference from Example 3-Formula 3 is that no skin microecological regulation components were added, the missing components were made up with deionized water, and the remaining components and preparation process are the same.

[0043] Comparative Example 2

[0044] The difference from Example 3-Formula 3 is that: no Paeonia lactiflora seed extract was added, the missing components were made up with deionized water, and the remaining components and preparation process are the same.

[0045] Comparative Example 3

[0046] The difference from Example 3-Formulation 3 is that the ceramide mixture is replaced with single ceramide 3, while the other components and preparation process are the same.

[0047] Comparative Example 4

[0048] The difference from Example 3-Formula 3 is that the plant extract complex contains only Phellodendron bark as a single component, and the missing components are made up by deionized water. The other components and preparation process are the same.

[0049] Comparative Example 5

[0050] The difference from Example 3-Formula 3 is that the plant extract complex consists of 0.94g of Phellodendron bark, 1.56g of Artemisia annua, and 2.81g of Sophora flavescens, and the missing components are made up with deionized water.

[0051] I. In vitro testing

[0052] To evaluate the in vitro bioactivity of the facial mask essence of the present invention, the following test methods were used:

[0053] 1. Anti-inflammatory activity assay (RAW 264.7 macrophage model)

[0054] (1) Cell culture: RAW 264.7 cells were seeded in 96-well plates (5×10⁶ cells / wells). 4 (each well contains 10 fetal bovine serum cells) and cultured in DMEM medium containing 10% fetal bovine serum in a 37°C, 5% CO2 incubator for 24 h.

[0055] (2) Sample processing: Set up Example 3-Formula 3 group, Comparative Examples 1-5 group and blank control group, respectively add culture medium containing different concentrations of essence (0.1%, 0.5%, 1.0%), each group has 3 replicates, and after pretreatment for 2h, add LPS (final concentration 1μg / mL) for stimulation for 24h.

[0056] (3) Detection indicators: The levels of IL-6 and TNF-α inflammatory factors in cell supernatant were measured using an ELISA kit, and the inhibition rate was calculated.

[0057] 2. Skin barrier repair test (HaCaT keratinocyte model)

[0058] (1) Cell scratch test: HaCaT cells were seeded in 6-well plates and cultured until the confluence reached 90%. The cells were then scratched with a sterile pipette tip, washed with PBS, and added to serum-free medium containing 1.0% essence. The cells were photographed at 0h, 12h, and 24h and the scratch healing rate was calculated.

[0059] (2) Tight junction protein detection: The expression levels of Claudin-1 and ZO-1 proteins were determined by Western blot, with β-actin as an internal reference.

[0060] 3. Test Results

[0061] (1) Results of anti-inflammatory activity test

[0062]

[0063] (2) Skin barrier repair test results

[0064]

[0065]

[0066] The results in Table 1-3 show that:

[0067] The facial mask essence of this invention exhibited significant anti-inflammatory activity and skin barrier repair ability in in vitro experiments. The specific results are as follows: Anti-inflammatory activity: The inhibition rates of IL-6 and TNF-α in the 1.0% Example 3-Formulation 3 group reached 82.5±3.8% and 79.6±4.1%, respectively, which were significantly better than the control group; Skin barrier repair: The cell scratch healing rate at 24h was 82.3±4.5%, and the expression levels of tight junction proteins Claudin-1 and ZO-1 were 2.3±0.2 and 1.9±0.15, respectively, which were 1.3 times and 0.9 times higher than the blank control group.

[0068] II. Effect Test

[0069] To verify the effect of the mask of the present invention on improving targeted drug-induced rashes, the following experimental design was conducted:

[0070] 1. Subject selection: 120 cancer patients who developed grade II-III acne-like rashes after receiving EGFR inhibitor treatment were selected. They were pathologically diagnosed with lung adenocarcinoma with EGFR mutation and developed rashes after oral administration of EGFR-TKIs (including erlotinib, ametinib, vormetinib, gefitinib, osimertinib, afatinib, icotinib, etc.). There were no dropouts during the study. They were randomly divided into 6 groups of 20 patients each, corresponding to Examples 3-Formulation 3 and Comparative Examples 1-5, respectively.

[0071] 2. Usage: After cleansing their face daily, all subjects should apply the corresponding group mask to the affected area for 20 minutes, once a day, for 28 consecutive days.

[0072] 3. Evaluation indicators:

[0073] (1) Severity of rash: The NCI-CTCAE 5.0 standard was used to record the rash grade (0-4) before use (baseline), on day 7, day 14 and day 28.

[0074] (2) Skin barrier function: The water content of the stratum corneum was measured using a transepidermal water loss meter (TEWL), and the pH of the skin surface was measured using a pH meter;

[0075] (3) Anti-inflammatory effect: Tissue fluid was collected from the lesion site, and the levels of IL-6 and TNF-α inflammatory factors were detected;

[0076] (4) Safety assessment: Record the incidence of adverse reactions such as skin irritation and allergies during use.

[0077] 4. Data statistics: SPSS 26.0 was used for analysis of variance. P < 0.05 was considered statistically significant.

[0078] 5. Test Results

[0079]

[0080] .

[0081]

[0082] 5.4 Security Assessment

[0083] No adverse reactions occurred in the above-described embodiments and comparative examples.

[0084] 5.5 Conclusion

[0085] The mask of this invention can significantly reduce the severity of targeted drug-induced rashes, improve skin barrier function, inhibit inflammatory factor levels, and has good safety. Its overall effect is superior to that of each comparative group (P<0.05).

[0086] 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 facial mask for targeted drug-induced rashes, characterized in that, The product comprises the following raw materials: a mask substrate and an essence loaded on the mask substrate. The active ingredients of the essence include the following components by weight percentage: 0.01-0.1% anti-inflammatory component, 0.5-2% ceramide mixture, 1-5% plant extract complex, 5-10% moisturizer, and the balance being solvent.

2. A facial mask for targeted drug-induced rashes as described in claim 1, characterized in that, The anti-inflammatory component comprises Salvia splendens seed extract, and the weight ratio of Salvia splendens to acetyl tetrapeptide-15 is (0.4-1.0):

1.

3. A facial mask for targeted drug-induced rashes as described in claim 2, characterized in that, The *Spiraea japonica* seed extract is obtained by crushing *Spiraea japonica* seeds, passing them through a 40-60 mesh sieve to obtain coarse powder, mixing the coarse powder with an ethanol aqueous solution of 50-70% v / v at a material-to-liquid ratio of 1:8-12, and performing ultrasonic-assisted extraction 1-3 times at 50-65℃, each time for 30-60 minutes; the ultrasonic power is 200-400W. The extracts are combined, filtered, and the filtrate is concentrated under reduced pressure at 50-60℃ and -0.08 to -0.10 MPa until no alcohol odor is detected, to obtain *Spiraea japonica* seed extract paste, which is then freeze-dried and crushed to obtain the *Spiraea japonica* seed extract.

4. A facial mask for targeted drug-induced rashes as described in claim 1, characterized in that, The ceramide mixture is composed of ceramide 3, ceramide 6II, and ceramide 1 mixed in a weight ratio of (2-4):(1-3):1, and the ceramide is a plant-derived synthetic ceramide with a purity ≥95%.

5. A facial mask for targeted drug-induced rashes as described in claim 1, characterized in that, The plant extract complex is a mixed extract complex of Phellodendron bark, Artemisia annua, Sophora flavescens, and Sanguisorba officinalis.

6. A facial mask for targeted drug-induced rashes as described in claim 1, characterized in that, The moisturizer is composed of sodium hyaluronate, betaine, and sodium polyglutamate mixed in a weight ratio of (1-3):(2-4):1, wherein the molecular weight of sodium hyaluronate is 800-1500 kDa.

7. A facial mask for targeted drug-induced rashes as described in claim 1, characterized in that, The solvent is a mixture of deionized water, propylene glycol and glycerin in a mass ratio of (4-6):(2-4):

2.

8. A facial mask for targeted drug-induced rashes as described in claim 1, characterized in that, The serum also contains skin microecological regulating components, which are α-glucan oligosaccharides and / or inulin.

9. A method for preparing a facial mask for targeted drug-induced rashes as described in any one of claims 1-8, characterized in that, Includes the following steps: S1. Preparation of plant extract complex: Phellodendron bark, Artemisia annua, Sophora flavescens and Sanguisorba officinalis are mixed in a weight ratio of (1-3):(2-5):(4-9):1, pulverized to 100-200 mesh, and 5-10 times the weight of 30-50% (v / v) ethanol aqueous solution is added. The mixture is ultrasonically extracted 1-3 times at 35-45℃ and 100-150W for 30-60 minutes each time. The extracts are combined, filtered through a ceramic membrane, and vacuum concentrated until there is no alcohol odor to obtain plant extract concentrate. S2. Add the ceramide mixture to glycerin and stir to dissolve at 60-70℃ and 300-500r / min. After cooling to 30-40℃, add the anti-inflammatory peptide and plant extract concentrate and stir at 100-200r / min for 15-30 minutes to obtain the active ingredient dispersion. S3. Preparation of the serum: Add the moisturizer and solvent to the active ingredient dispersion in sequence, stir until completely dissolved, adjust the pH to 5.5-6.5, and then filter through a 0.22μm polyethersulfone filter membrane for sterilization; S4. Mask Forming: The sterile essence is combined with the pre-treated mask substrate and soaked for 2-4 hours to make the essence load reach 200-300% of the weight of the substrate. Then it is packaged.

10. A method for preparing a facial mask for targeted drug-induced rashes as described in claim 9, characterized in that, In step S1, the pore size of the ceramic membrane is 50-100 nm, the vacuum concentration temperature is 40-50 °C, and the vacuum degree is -0.08~-0.09 MPa. The mask substrate is a nano-biocellulose substrate. The nanofiber is a composite of hyaluronic acid and polyvinyl alcohol. The fiber diameter is 100-500 nanometers, the porosity is 80-90%, and the thickness is 0.1-0.3 mm. The substrate surface is pretreated with plasma with a power of 50-80W for 3-5 minutes.

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