Solid-state flash-release acne-removing composition and application thereof in soluble microneedle

Abstract

The invention discloses a solid-state flash-release acne-removing composition and an application thereof in a soluble microneedle, and particularly belongs to the technical field of cosmetics. The acne-removing composition is prepared from the following components in parts by mass: 0.5 to 1 part of acne-removing functional component, 4 to 5 parts of hyaluronic acid and 1 to 2 parts of carboxymethyl cellulose, the acne-removing functional component contains a spruce extract, a yeast / zinc fermentation product and dipeptide-15, and the spruce extract is prepared through supercritical extraction. The soluble microneedle containing the acne-removing composition is prepared by utilizing a soluble microneedle preparation technology, and the effects of quickly resisting inflammation, inhibiting bacteria and quickly transdermal repairing can be achieved.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics, and in particular, relates to a solid-state flash-release acne-removing composition and its application in soluble microneedles. Background Art

[0002] Acne, a chronic inflammatory skin disease with high prevalence worldwide, is driven by multiple factors, including hypersecretion of sebum, overgrowth of Propionibacterium acnes, and activation of the inflammatory response. Current mainstream acne treatments still suffer from shortcomings: 1. Low transdermal efficiency: Traditional topical medications, due to the stratum corneum barrier, have limited penetration of active ingredients, making it difficult for them to reach acne lesions in the dermis. 2. Inactivation of active ingredients: Conventional cream systems cannot guarantee the stability of anti-inflammatory and antibacterial ingredients, which are prone to degradation and loss of efficacy during storage. 3. Slow and limited onset of action: Existing products often target a single mechanism (such as antibacterial or oil control), lacking a multi-pathway synergistic approach, requiring continuous, prolonged use to be effective.

[0003] Therefore, developing an anti-acne composition that can synergistically exhibit anti-inflammatory, antibacterial, and repair functions and achieve solid-state flash release through an efficient delivery system has become a key direction to break through the industry's technical bottlenecks. Summary of the Invention

[0004] In view of the deficiencies of the prior art, the object of the present invention is to provide an acne-removing composition that can synergistically exert anti-inflammatory, antibacterial and repairing functions and achieve solid-state flash release through an efficient delivery system.

[0005] To achieve the above objectives, the present invention discloses the following technical solutions: In a first aspect, the present invention provides a solid-state flash-release acne-removing composition, which comprises the following components in parts by mass: 0.5-1 part of acne-removing component; 4-5 parts of hyaluronic acid; 1-2 parts of carboxymethyl cellulose; The acne-removing component contains spruce extract, yeast / zinc fermentation product and dipeptide-15.

[0006] Preferably, the mass ratio of spruce extract, yeast / zinc fermentation product and dipeptide-15 in the anti-acne efficacy component is (4-6): (0.1-0.3): (0.5-1).

[0007] Further preferably, the preparation method of the spruce extract comprises the following steps: Step 1.1. Grind and sieve dried spruce leaves to obtain spruce powder; Step 1.2. Place the spruce powder in a supercritical CO2 extraction vessel for 2-3 hours, and collect the extract. Step 1.3. The extract is concentrated under reduced pressure and dried to obtain a spruce extract.

[0008] More preferably, the extraction parameters in step 1.2 are extraction pressure 28-30 MPa, extraction temperature 35-42°C, entrainer 60-70 v / v% ethanol, CO2 fluid flow rate 1-2 L / h, entrainer flow rate 0.02-0.04 L / h, and the extract is collected.

[0009] In a second aspect, the present invention provides a solid-state flash-release soluble microneedle patch, wherein the soluble microneedle patch contains the anti-acne composition described in the first aspect.

[0010] In a third aspect, the present invention provides a method for preparing the solid-state flash-release soluble microneedle patch according to the second aspect, the preparation method comprising the following steps: Step 2.1. Preparation of microneedle solution: dissolving the anti-acne composition in deionized water to obtain microneedle solution; Step 2.2. Preparation of the needle-carrying layer stock solution: Add deionized water to polyvinyl alcohol and stir to dissolve to obtain the needle-carrying layer stock solution; Step 2.3. Mold casting: inject the microneedle liquid into the microneedle mold, place the microneedle mold filled with the microneedle liquid at 2500-3500rpm for centrifugation for 10-15min, then place the mold at 30-40℃ to dry for 10-15h, add the needle layer stock solution after drying, place it at 30-40℃ to dry for 10-15h, and remove the mold after drying to obtain a flash-release soluble microneedle patch.

[0011] Preferably, the mass ratio of the anti-acne composition to deionized water in step 2.1 is 6:(95-100).

[0012] Preferably, in step 2.2, the mass ratio of polyvinyl alcohol to deionized water is 1:(9-10), and the mixture is stirred and dissolved uniformly at 80-90° C. to obtain the needle-carrying layer stock solution.

[0013] Preferably, the microneedle mold in step 2.3 has microneedle-shaped depressions arranged in an array, and the microneedle arrangement density is 200-300 pieces / cm 2 , microneedle depth 200-500μm.

[0014] In a fourth aspect, the present invention provides the use of the solid-state flash-release acne-removing composition described in the first aspect in the preparation of soluble microneedles with anti-inflammatory, acne-removing and antibacterial effects.

[0015] In the present invention: Spruce leaves are rich in flavonoids (such as quercetin and kaempferol) and terpenoid active ingredients, endowing them with significant anti-inflammatory, antibacterial, and antioxidant properties. They effectively inhibit the NF-κB inflammatory signaling pathway and reduce the release of key pro-inflammatory factors such as IL-1β and TNF-α. They exhibit strong antibacterial activity against Propionibacterium acnes, primarily by disrupting the integrity of bacterial cell membranes. Furthermore, their antioxidant activity helps scavenge free radicals and alleviate oxidative stress damage caused by acne. The spruce extract provided by the present invention is produced using supercritical CO2 extraction technology, which prevents degradation of heat-sensitive substances and highly retains active ingredients.

[0016] Yeast / zinc fermentation products convert inorganic zinc into organic chelated zinc through microbial fermentation, and are rich in active ingredients such as yeast peptides, amino acids, nucleotides, etc., and have the quadruple effects of oil control, antibacterial, repair, and antioxidant: it can inhibit the activity of 5α-reductase, significantly reduce sebum secretion, inhibit pathogenic bacteria such as Propionibacterium acnes, and reduce inflammation; at the same time, it promotes the renewal of keratinocytes, strengthens the barrier and reduces water loss; it can also scavenge free radicals and delay photoaging.

[0017] Dipeptide-15 is a synthetic small molecule peptide that mainly plays a soothing, anti-allergic and barrier-strengthening role in skin care: it quickly relieves sensitive reactions such as stinging and redness by inhibiting the release of inflammatory factors (such as IL-6 and TNF-α); at the same time, it promotes keratinocytes to produce natural moisturizing factors and lipids, enhances the integrity of the stratum corneum, reduces transepidermal water loss, and accelerates skin repair.

[0018] Beneficial effects of the present invention: This invention achieves triple breakthrough advantages through the synergistic combination of spruce extract, yeast / zinc fermentation products and dipeptide-15, combined with the targeted delivery technology of soluble microneedles: Highly effective anti-inflammatory and antibacterial properties: The spruce extract and yeast / zinc fermentation products in the composition work synergistically to significantly reduce the release of inflammatory factors and the activity of pathogenic bacteria; Rapid transdermal repair: Soluble microneedles reach deep into acne lesions, dissolving and releasing active ingredients. Dipeptide-15 promotes collagen regeneration, and yeast / zinc fermentation products accelerate wound healing. In a 10-day human evaluation, 95% of users experienced over 80% reduction in acne. Process efficiency guarantee: Supercritical CO2 extraction of spruce extract ensures the purity of active ingredients. Combined with the solid-state stabilization system of flash-release microneedles, it overcomes the defects of low skin penetration and slow onset of traditional acne treatment products, providing a new solution for acne treatment. DETAILED DESCRIPTION

[0019] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0020] To further illustrate the present invention, the following examples are provided for detailed description. The raw materials used in the following examples and comparative examples are all commercially available products; the raw material companies listed below are one of the sources for purchasing the raw materials.

[0021] In the present invention: Spruce leaves: leaves of the European spruce (PICEA EXCELSA) of the Abies subfamily; Yeast / zinc fermentation product: purchased from Guangzhou Youran Biotechnology Co., Ltd.; Dipeptide-15: purchased from Shenzhen Vicky Technology Co., Ltd.; Hyaluronic acid: purchased from Bloomage Biotechnology; Carboxymethyl cellulose: purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0022] Preparation of spruce extract: Step 1. Take spruce leaves and place them in a constant temperature drying oven to dry to constant weight. The dried spruce leaves are then placed in a grinder and crushed through a 30-mesh sieve to obtain spruce powder; Step 2. Place the spruce powder into a supercritical CO2 extraction kettle and adjust the extraction parameters: extraction pressure 30 MPa, extraction temperature 42°C, entrainer 70 v / v% ethanol, CO2 fluid flow rate 1.2 L / h, entrainer flow rate 0.03 L / h, extraction time 2.5 h, and collect the extract; Step 3. Concentrate the extract under reduced pressure and dry it to obtain the spruce extract.

[0023] Preparation of anti-acne composition: The raw materials were compounded according to the mass ratio in Table 1 to obtain an acne-removing composition; Table 1 Mass ratio of efficacy composition Raw material name Composition 1 Composition 2 Composition 3 Spruce Extract 4 5 6 Saccharomyces / zinc ferment 0.1 0.2 0.3 Dipeptide-15 0.5 0.7 1 The raw materials were compounded according to the mass ratio in Table 2 to obtain a comparative composition; Table 2 Mass ratio of comparative composition Raw material name Comparative composition 1 Comparative composition 2 Comparative composition 3 Comparative composition 4 Spruce Extract / 5 5 1 Saccharomyces / zinc ferment 0.2 / 0.2 1 Dipeptide-15 0.7 0.7 / 1 Note: “ / ” in the table means no additive.

[0024] Performance Testing 1 Anti-inflammatory test 1.1 Test Principle Currently, in vitro anti-inflammatory drug screening tests mainly use human acute mononuclear cells (THP-1) as a model, which is co-cultured with Propionibacterium acnes (live or heat-inactivated) to study the secretion and expression of related inflammatory factors such as human interleukin-1β (IL-1β). This is the most commonly used in vitro acne inflammation evaluation model.

[0025] 1.2 Trial Grouping Nine groups of experiments were set up, including one blank control group, one model group (negative control group), and seven drug-added groups, with six wells in each group. Model group: co-cultured with Propionibacterium acnes, no drug was given, and the same volume of culture medium as the test drug solution was given; Blank control group: no co-culture with Propionibacterium acnes, no drug, and the same volume of culture medium as the test drug solution was given; Treatment group: co-cultured with Propionibacterium acnes, administered at the same time, and co-cultivated with the corresponding test solution.

[0026] 1.3 Preparation of test solution 1 part by mass of composition 1-3 and comparative composition 1-4 were mixed and diluted with 99 parts by mass of RPMI-1640 culture medium to obtain test solutions 1-7, as shown in Table 3: Table 3 Group Preparation Test solution 1 1 part by mass of composition 1 and 99 parts by mass of culture medium Test solution 2 1 part by mass of composition 2 and 99 parts by mass of culture medium Test solution 3 1 part by mass of composition 3 and 99 parts by mass of culture medium Test solution 4 1 part by mass of comparative composition 1 and 99 parts by mass of culture medium Test solution 5 1 part by mass of comparative composition 2 and 99 parts by mass of culture medium Test solution 6 1 part by mass of comparative composition 3 and 99 parts by mass of culture medium Test solution 7 1 part by mass of comparative composition 4 and 99 parts by mass of culture medium 1.4 Test methods Take THP-1 in exponential growth phase and use 1×10 6 The cells were inoculated at a density of 100 / mL in a 96-well culture plate. Propionibacterium acnes cultured anaerobically for 72 hours was used to prepare a live bacterial suspension. Except for the blank group, the model group and the drug-treated group were added to the 96-well culture plate at a ratio of 100:1 between the number of bacteria and THP-1. Drugs were then administered according to the group settings. After culturing for 24 hours, the IL-1β content in the cell supernatant was determined by ELISA. The formula for calculating the IL-1β inhibition rate is shown in Equation (1). The results are shown in Table 4.

[0027] ; Where: A0——IL-1β content in model group; A1——IL-1β content in the drug-treated group.

[0028] 1.5 Test results Table 4 Effect of IL-1β content

[0029] Note: a indicates significant difference compared with the model group, P < 0.05, aa: P < 0.01; b indicates significant difference compared with composition 2, P < 0.05, bb: P < 0.01.

[0030] 1.6 Results Analysis As shown in Table 4, compared with the blank control group, Propionibacterium acnes induced THP-1 to secrete a large amount of inflammatory factors in the model group. Compared with the model group, compositions 1-3 and comparative compositions 1-4 were able to inhibit the secretion of IL-1β. Among them, the inhibitory effect of inflammatory factors of composition 1-3 was significantly better than that of comparative compositions 1-3, indicating that the anti-inflammatory effect of the composition is achieved by the interaction of the three components: spruce extract, yeast / zinc fermentation product, and dipeptide-15. The absence of any one of them will lead to a weakened anti-inflammatory effect. Comparative composition 4 also contains spruce extract, yeast / zinc fermentation product, and dipeptide-15, but the anti-inflammatory effect is not as good as composition 2, indicating that the three components must be combined in a certain mass ratio to achieve better efficacy.

[0031] 2 Inhibition test of Propionibacterium acnes 2.1 Test basis Propionibacterium acnes (GDMCC 1.243) was selected as the test strain. After three generations of culture, the antibacterial test was carried out according to "5.1.1 Quantitative antibacterial test of suspension" of WS / T650-2019 "Evaluation Methods for Antibacterial and Antibacterial Effects".

[0032] 2.2 Preparation of test solution 1 part by mass of composition 1-3 and comparative composition 1-4 were mixed and diluted with 9 parts by mass of PBS to obtain test solutions 1-7.

[0033] 2.3 Test methods Take the test bacteria and dilute them with PBS to about 5.0×10 5 CFU / mL~4.5×10 6 Prepare a CFU / mL bacterial suspension. Add 5.0 mL of the test solution to a sterile test tube. Place in a 20°C ± 1°C water bath for 5 minutes. Then, add 0.1 mL of the test bacterial suspension. Mix quickly and begin counting immediately. After 20 minutes, aspirate 1.0 mL of the test bacteria and test solution mixture and inoculate two plates. Pour the culture medium over the mixture. Simultaneously, replace the test solution with PBS and perform a parallel experiment as a positive control. Repeat the experiment three times. Calculate the inhibition rate (X) according to formula (2). The results are shown in Table 5.

[0034] ; Where: X——inhibition rate,%; A0——the amount of bacteria recovered in the positive control group, CFU / mL; A1——The amount of bacteria recovered from the test solution, CFU / mL.

[0035] 2.4 Test results Table 5 Antibacterial rate results Group Antibacterial rate / % Test solution 1 (composition 1) 96.88% Test solution 2 (composition 2) 98.53% Test solution 3 (composition 3) 97.65% Test solution 4 (comparative composition 1) 64.33% Test solution 5 (comparative composition 2) 57.90% Test solution 6 (comparative composition 3) 95.54% Test solution 7 (comparative composition 4) 91.15% 2.5 Results Analysis As shown in Table 5, compositions 1-3 exhibited a strong antibacterial effect, with an antibacterial rate against Propionibacterium acnes exceeding 95% at a concentration of 10%. This demonstrates that the compositions provided herein, when formulated in their entirety, can effectively control the growth of acne-causing bacteria in acne-prone skin, while simultaneously inhibiting inflammatory factors caused by harmful bacteria, soothing skin inflammation and achieving acne control and suppression. Although compositions 1-4 also exhibited a certain antibacterial effect, their overall effect was inferior to that of compositions 1-3. Therefore, the formulations of compositions 1-3 are more suitable for acne removal.

[0036] Preparation of flash-release soluble microneedle patch: Step 1. Preparation of microneedle solution: Disperse composition 2 in a hyaluronic acid / carboxymethyl cellulose aqueous solution, wherein the mass ratio of composition 2, hyaluronic acid, carboxymethyl cellulose and deionized water is 1:4:1:95 to obtain a microneedle solution; Step 2. Preparation of the needle-carrying layer stock solution: Add deionized water to polyvinyl alcohol at a mass ratio of 1:10, heat in a water bath to 90°C, and stir to dissolve to obtain the needle-carrying layer stock solution; Step 3. Mold casting: inject the microneedle liquid into the microneedle mold, which has microneedle-shaped depressions arranged in an array with a microneedle density of 200-300 / cm 2 The microneedle depth is 300μm. The microneedle mold containing the microneedle liquid is placed at 3000rpm for centrifugation for 10min to ensure that the microneedle liquid is distributed on the needle tip. The excess liquid in the mold is scraped off, and then the mold is placed at 40℃ to dry for 10h. After drying, the needle layer stock solution is added and placed at 30℃ to dry for 15h. After drying, the mold is removed to obtain a flash-release soluble microneedle patch.

[0037] Human body evaluation Effect evaluation object Forty male volunteers with obvious acne on both sides of their faces, who were in the new or inflammatory stage and whose facial skin was prone to acne, were selected and randomly divided into two groups, with 20 people in each group. One group used the flash-release soluble microneedle patch, and the other group used a certain brand of acne essence sold on the market.

[0038] How to use Flash-release soluble microneedle patch: After washing and drying your face in the morning, take the microneedle patch and press it on the acne area. Remove it after 10 minutes. Do this every other day for 10 days.

[0039] Commercially available anti-acne essence: After washing and drying your face every morning and evening, apply 2g of anti-acne essence to the acne area, and gently massage to ensure full absorption. Do this twice a day for 10 days.

[0040] Experimental results Table 6 Evaluation criteria\groups Flash-release soluble microneedle patch Commercially available acne serum Acne has subsided by more than 80%, redness and swelling have significantly subsided, and the pain and itching are no longer there (number of people) 19 0 Acne subsided by more than 50%, redness and swelling partially subsided, and pain and itching were reduced (number of people) 1 6 Acne subsided less than 50%, redness and swelling subsided little, acne pain and itching were obvious (number of people) 0 14 Result Analysis According to the test results, the flash-release soluble microneedle patch provided by the present invention has a good therapeutic and elimination effect on the facial acne of male volunteers in a short period of time. The flash-release soluble microneedle patch of the present invention penetrates deep into the skin through the antibacterial and anti-inflammatory effects of spruce extract, yeast / zinc fermentation products, and dipeptide-15, combined with the characteristics of soluble microneedles, and reaches directly to the center of the affected area, achieving a synergistic effect, improving the effect of the effective components, and enabling it to relieve acne inflammatory reactions in a short period of time, thereby achieving the effect of quickly removing and suppressing acne.

[0041] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art will be able to modify the technical solutions described in the aforementioned embodiments or substitute equivalents for some of the technical features. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A solid-state flash-release anti-acne composition, characterized in that: The anti-acne composition contains the following components in parts by mass: 0.5-1 part of acne-removing component; 4-5 parts of hyaluronic acid; 1-2 parts of carboxymethyl cellulose; The acne-removing component contains spruce extract, yeast / zinc fermentation product and dipeptide-15.

2. The anti-acne composition according to claim 1, characterized in that The mass ratio of spruce extract, yeast / zinc fermentation product and dipeptide-15 in the acne-removing efficacy component is (4-6): (0.1-0.3): (0.5-1).

3. The anti-acne composition according to claim 1 or 2, characterized in that The preparation method of the spruce extract comprises the following steps: Step 1.

1. Grind and sieve dried spruce leaves to obtain spruce powder; Step 1.

2. Place the spruce powder in a supercritical CO2 extraction vessel for 2-3 hours, and collect the extract. Step 1.

3. The extract is concentrated under reduced pressure and dried to obtain a spruce extract.

4. The anti-acne composition according to claim 3, characterized in that The extraction parameters in step 1.2 are extraction pressure 28-30 MPa, extraction temperature 35-42° C., entrainer 60-70 v / v% ethanol, CO2 fluid flow rate 1-2 L / h, entrainer flow rate 0.02-0.04 L / h, and the extract is collected.

5. A solid-state flash-release soluble microneedle patch, characterized in that: The soluble microneedle patch contains the anti-acne composition according to any one of claims 1 to 4.

6. The method for preparing the soluble microneedle patch according to claim 5, characterized in that: The preparation method comprises the following steps: Step 2.

1. Preparation of microneedle solution: dissolving the anti-acne composition in deionized water to obtain microneedle solution; Step 2.

2. Preparation of the needle-carrying layer stock solution: Add deionized water to polyvinyl alcohol and stir to dissolve to obtain the needle-carrying layer stock solution; Step 2.

3. Mold casting: inject the microneedle liquid into the microneedle mold, place the microneedle mold filled with the microneedle liquid at 2500-3500rpm for centrifugation for 10-15min, then place the mold at 30-40℃ to dry for 10-15h, add the needle layer stock solution after drying, place it at 30-40℃ to dry for 10-15h, and remove the mold after drying to obtain a flash-release soluble microneedle patch.

7. The preparation method according to claim 6, characterized in that The mass ratio of the anti-acne composition to deionized water in step 2.1 is 6:(95-100).

8. The preparation method according to claim 6, characterized in that In the step 2.2, the mass ratio of polyvinyl alcohol to deionized water is 1:(9-10), and the mixture is stirred and dissolved uniformly at 80-90° C. to obtain a needle-carrying layer stock solution.

9. The preparation method according to claim 6, characterized in that In step 2.3, the microneedle mold has microneedle-shaped depressions arranged in an array, and the microneedle arrangement density is 200-300 pieces / cm 2 , microneedle depth 200-500μm.

10. Use of the solid-state flash-release anti-acne composition according to any one of claims 1 to 4 in the preparation of soluble microneedles with anti-inflammatory, anti-acne and antibacterial effects.

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