A composition for treating acne, liposomes and a preparation method and application thereof

Abstract

The present application relates to the cosmetic technical field, especially to a kind of acne-removing composition, liposome and its preparation method and application.The acne-removing composition includes the following weight parts of components: nicotinamide 2-8 parts, magnolia bark extract 1-5 parts, glycyrrhizinic acid 0.15-2.01 parts, persicin 0.1-2 parts, hyssop extract 0.01-0.15 parts.The present application uses nano carrier to wrap and deliver the acne-removing composition, increases the solubility of active ingredient, improves the bioavailability of active ingredient, also improves the irritability of active ingredient, realizes multi-target co-delivery, multi-mechanism acne-removing, and has significant acne-removing effect.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and in particular to an acne-removing composition, liposomes, their preparation methods and applications. Background Technology

[0002] Acne is a chronic inflammatory skin disease that affects the pilosebaceous unit and commonly occurs on the cheeks, back, and chest. It can occur in people of all ages, but the incidence is highest among adolescents.

[0003] The pathogenesis of acne is quite complex. The mainstream view is that it is related to the following four aspects: excessive lipid secretion under the influence of androgens, abnormal keratinization of the pilosebaceous duct (acne formation), massive proliferation of microorganisms in the hair follicle, and inflammation and immune response.

[0004] The mechanisms of acne treatment are complex. Although there are many acne-fighting skincare products on the market, their mechanisms are often limited. Most products use acid peels to achieve acne-fighting effects, but this can easily lead to over-cleansing and damage the skin barrier. Many active ingredients with acne-fighting properties, such as vitamins and their derivatives, and polypeptides, are sensitive to enzymes, light, heat, and pH levels. They are highly irritating, unstable, easily degraded and inactivated, and have poor transdermal absorption. Direct application in cosmetic products can easily lead to oxidative denaturation or inactivation, thus affecting their skincare effects on the targeted areas. Furthermore, the stratum corneum of the skin has a strong keratinocyte barrier function, making it difficult for active molecules to penetrate, ultimately resulting in a significant reduction in acne-fighting effectiveness. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the existing technology and provide an acne-removing composition and liposome that can be co-delivered to multiple targets and remove acne through multiple mechanisms, with significant acne-removing effects.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] In a first aspect, the present invention provides an acne-removing composition comprising the following components in parts by weight: 2-8 parts niacinamide, 1-5 parts magnolia bark extract, 0.15-2.01 parts glycyrrhetinic acid, 0.1-2 parts tau tannin, and 0.01-0.15 parts senna extract.

[0008] This invention comprehensively considers multiple acne-removing mechanisms and combines niacinamide, magnolia bark extract, glycyrrhetinic acid, tau salsa extract, and senna extract to obtain an acne-removing composition (named ACNITECH in this invention): Niacinamide promotes skin metabolism, removes excess keratin, controls sebum secretion, inhibits melanin transfer, fades acne scars, and evens out skin tone.

[0009] The extract of Magnolia officinalis bark in this application has anti-inflammatory and antioxidant effects, and can effectively inhibit the excessive proliferation of pathogens such as Propionibacterium acnes.

[0010] In this application, glycyrrhetinic acid is described as a highly active anti-inflammatory ingredient that inhibits the production of inflammatory factors, reduces skin inflammation, and enhances skin immunity.

[0011] In this application, tau phenol can inhibit Propionibacterium acnes, reduce inflammation, and help improve acne and pimples; regulate sebum secretion, making it suitable for oily and combination skin, and helping to keep the skin fresh; and has anti-inflammatory and repairing effects, making it suitable for sensitive skin, and able to relieve redness and irritation.

[0012] In this application, the extract of sage has antibacterial and anti-inflammatory effects, helping to prevent and improve skin problems such as acne, and relieving skin inflammation and redness; it has soothing and repairing effects, suitable for sensitive skin, and can relieve skin irritation and discomfort; it also has a certain astringent effect, helping to shrink pores and improve skin texture. The above-mentioned active ingredients are scientifically and rationally combined within the scope of this invention, targeting and intervening in the skin through the following pathways: increased sebum secretion and changes in its composition; excessive keratinization of the follicular stratum corneum; increased proliferation of Propionibacterium acnes and biofilm formation in the pilosebaceous glands; inflammatory responses in the skin; inhibition of hyperresponsiveness; and changes in the skin's microecological environment, resulting in significant acne-removing effects.

[0013] Preferably, the mass ratio of glycyrrhetinic acid to senna extract is glycyrrhetinic acid: senna extract = (15-20): 1.

[0014] Extensive research has revealed that when glycyrrhetinic acid and senna extract are combined in a specific ratio, the glycyrrhetinic acid's glucocorticoid-like effects and senna's direct pathway inhibition create a dual regulatory effect, covering both upstream and downstream of the inflammatory response (e.g., glycyrrhetinic acid inhibits transcription factors, while senna blocks signal transduction). This combination enhances the bioavailability of both components, resulting in optimal anti-inflammatory and acne-reducing effects. However, excessive amounts of either component may lead to competitive inhibition: for example, high concentrations of glycyrrhetinic acid may inhibit the effects of certain terpenes in senna, leading to a decrease in efficacy.

[0015] Secondly, the present invention provides an acne-removing liposome, the acne-removing liposome comprising the above-mentioned acne-removing composition and liposome carrier excipients; the liposome carrier excipients comprising phospholipids, emulsifiers, co-emulsifiers, polyols and water.

[0016] Nanoliposomes generally refer to small, single-chambered liposomes with a particle size of less than 100 nm. They can encapsulate water-soluble or lipid-soluble active ingredients and have advantages such as sustained release, biodegradability, and non-immunogenicity and toxicity. Their nanoscale size and good deformability give them a strong ability to penetrate physiological tissue barriers. Nanocarriers used in cosmetics can significantly improve the skin penetration of active ingredients.

[0017] This invention utilizes novel nanotechnology to encapsulate and deliver a scientifically formulated acne-removing composition using a nanocarrier. Based on the structure and properties of the nanocarrier, the nano-encapsulated acne-removing composition exhibits excellent stability and water dispersibility, increasing the solubility of the active ingredients while also reducing their irritation. Through skin delivery, it achieves sustained release and long-lasting effects, while simultaneously targeting multiple points and significantly enhancing efficacy.

[0018] Preferably, the average particle size of the acne-removing liposomes is 24.68 nm-29.52 nm.

[0019] Preferably, the acne-removing liposome comprises the following components by weight percentage: 3.26-17.1% acne-removing composition, 0.1-5% phospholipids, 10-30% emulsifier, 1-5% co-emulsifier, 10-40% polyol, and the balance being water.

[0020] Preferably, the phospholipid includes at least one of soybean lecithin, hydrogenated lecithin, egg yolk lecithin, hydrogenated soybean lecithin, and hydrogenated egg yolk lecithin.

[0021] Preferably, the emulsifier includes at least one of polyoxyethylene castor oil emulsifiers, polyoxyethylene hydrogenated castor oil emulsifiers, polyglycerol emulsifiers, poloxamer, cocoyl glucoside, triglycerides, pyrrolidones, polyglycerol esters, polyglycerol lactate, polyglycerol stearate, polyglycerol caprylate / capric acid ester, polyglycerol laurate, Tween 80, Tween 20, Tween 60, PEG-20 hydrogenated castor oil, PEG-40 hydrogenated castor oil, and PEG-60 hydrogenated castor oil.

[0022] Preferably, the co-emulsifier includes at least one of lauryl alcohol polyether-23, diethylene glycol monoethyl ether, PPG-26-butanol polyether-26, and tridecyl alcohol polyether-12.

[0023] Preferably, the polyol comprises at least one of glycerol, propylene glycol, 1,3-butanediol, 2,3-butanediol, 1,3-propanediol, 1,2-pentanediol, ethoxydiethylene glycol, 1,2-hexanediol, dipropylene glycol, isopropanol, polyethylene glycol-200, PPG-10 sorbitol, octyldodecyl alcohol, and butylene glycol.

[0024] Thirdly, the present invention provides a method for preparing the acne-removing liposomes, comprising the following steps:

[0025] (1) Mix the Magnolia officinalis bark extract, glycyrrhetinic acid, tau phenol, emulsifier, co-emulsifier, polyol and phospholipid to obtain mixture A;

[0026] (2) Mix nicotinamide, thyme extract and water to obtain mixture B;

[0027] (3) Pour mixture A into mixture B and mix thoroughly to obtain mixture C;

[0028] (4) The mixture C is nano-sized to obtain the acne-removing liposome.

[0029] Preferably, the nano-sizing process includes extrusion, ultrasonication, or homogenization.

[0030] Preferably, the homogenization condition is a treatment at 500-1000 bar.

[0031] Preferably, the processing conditions for the uniform mixing in steps (1)-(3) are 45-65℃, and the mixture is stirred evenly.

[0032] Fourthly, the present invention provides the use of the acne-removing composition or the acne-removing liposome in acne-removing products.

[0033] The acne-removing liposomes obtained in this invention are used to prepare acne-removing products. The active ingredients are delivered via liposomes, allowing the product to reach a sufficient concentration to exert its corresponding functional effects. This effectively improves the solubility of each active ingredient while providing a stable storage space, preventing unnecessary degradation or inactivation of the active ingredients before storage and use, thus facilitating a higher concentration of active ingredients in acne-removing products.

[0034] Fifthly, the present invention provides an acne treatment product, comprising the acne treatment composition or the acne treatment liposome.

[0035] The beneficial effects of this invention are as follows:

[0036] This invention comprehensively considers multiple acne-removing mechanisms, combining niacinamide, magnolia bark extract, glycyrrhetinic acid, tau salsa extract, and senna extract to obtain an acne-removing composition. The active ingredients, through scientific and rational combination, target and intervene in the following pathways to regulate and treat the skin: increased sebum secretion and changes in its composition; excessive keratinization of the follicular stratum corneum; increased proliferation of Propionibacterium acnes and biofilm formation within the pilosebaceous glands; skin inflammatory response; inhibition of hyperresponsiveness; and alteration of the skin's microecological environment, resulting in significant acne-removing efficacy.

[0037] This invention utilizes novel nanotechnology to encapsulate and deliver a scientifically formulated acne-fighting composition using a nanocarrier. Based on the structure and properties of the nanocarrier, a liposome for acne treatment is obtained through nano-encapsulation. This liposome exhibits excellent stability and water dispersibility, increasing the solubility of the active ingredients while also reducing their irritation. This allows the active ingredients to reach sufficient concentrations in the product to exert their corresponding functional effects. While effectively improving the solubility of each active ingredient, it also provides a stable storage space, preventing unnecessary degradation or inactivation of the active ingredients before storage and use, thus contributing to a higher concentration of active substances in the acne-fighting product. Attached Figure Description

[0038] Figure 1 This is an electron micrograph of the acne-removing liposomes prepared according to the present invention. Detailed Implementation

[0039] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0040] The Magnolia officinalis bark extract and Herba Senna extract described in this invention were purchased from Xi'an Shilin Technology Co., Ltd. Experimental studies in this invention have shown that the extraction method does not affect their efficacy.

[0041] Example 1:

[0042] One embodiment of the acne-removing liposome of the present invention includes an acne-removing composition and a liposome carrier excipient.

[0043] The acne-removing liposome comprises the following components by weight percentage:

[0044] Nicotinamide 8%, Magnolia officinalis bark extract 5%, glycyrrhetinic acid 2%, tau tannin 2%, senna extract 0.1%, phospholipids 5%, emulsifier 30%, co-emulsifier 5%, polyol 40%, water to 100%.

[0045] The phospholipid is soybean lecithin;

[0046] The emulsifier contains 10% polyglycerol lauryl ester, 15% cocoyl glucoside, and 5% Tween 80;

[0047] The co-emulsifier is lauryl alcohol polyether-23;

[0048] The polyol comprises 10% 1,2-pentanediol, 20% glycerol, and 10% ethoxydiethylene glycol.

[0049] The preparation method of the acne-removing liposomes includes the following steps:

[0050] (1) Mix the Magnolia officinalis bark extract, glycyrrhetinic acid, tau tannin, emulsifier, co-emulsifier, polyol and phospholipid, and stir at 45°C to form a homogeneous and clear mixture A.

[0051] (2) Mix nicotinamide, thyme extract and water, and stir at 45°C to form a homogeneous and clear mixture B;

[0052] (3) Pour mixture A into mixture B and mix evenly. Stir at 45°C to form a homogeneous mixture C.

[0053] (4) The mixture C was subjected to high pressure homogenization at 1000 bar, 3 times, and cooled to room temperature to obtain the acne-removing liposome.

[0054] Example 2:

[0055] One embodiment of the acne-removing liposome of the present invention includes an acne-removing composition and a liposome carrier excipient.

[0056] The acne-removing liposome comprises the following components by weight percentage:

[0057] Niacinamide 5%, Magnolia officinalis bark extract 3%, glycyrrhetinic acid 1%, tau phenol 1%, senna extract 0.06%, phospholipids 3%, emulsifier 20%, co-emulsifier 3%, polyol 30%, water to 100%.

[0058] The phospholipid is hydrogenated lecithin;

[0059] The emulsifier contains 5% Tween 80, 10% cocoyl glucoside, and 5% poloxamer;

[0060] The co-emulsifier is PPG-26-butanol polyether-26;

[0061] The polyol contains 10% 1,2-hexanediol and 20% 1,3-propanediol.

[0062] The preparation method of the acne-removing liposomes includes the following steps:

[0063] (1) Mix the Magnolia officinalis bark extract, glycyrrhetinic acid, tau phenol, emulsifier, co-emulsifier, polyol and phospholipid, and stir at 50°C to form a homogeneous and clear mixture A.

[0064] (2) Mix nicotinamide, thyme extract and water, and stir at 50°C to form a homogeneous and clear mixture B;

[0065] (3) Pour mixture A into mixture B and mix well. Stir at 50°C to form a homogeneous mixture C.

[0066] (4) The mixture C was subjected to high pressure homogenization at 800 bar, 3 times, and cooled to room temperature to obtain the acne-removing liposome.

[0067] Example 3:

[0068] One embodiment of the acne-removing liposome of the present invention includes an acne-removing composition and a liposome carrier excipient.

[0069] The acne-removing liposome comprises the following components by weight percentage:

[0070] Niacinamide 3%, Magnolia officinalis bark extract 2%, glycyrrhetinic acid 0.5%, tau phenol 0.8%, senna extract 0.03%, phospholipids 1%, emulsifier 15%, co-emulsifier 2%, polyol 20%, water to 100%.

[0071] The phospholipid is hydrogenated soybean lecithin;

[0072] The emulsifier contains 10% PEG-20 hydrogenated castor oil and 5% Tween 20;

[0073] The co-emulsifier is diethylene glycol monoethyl ether;

[0074] The polyol contains 10% 1,2-hexanediol and 10% isopropanol.

[0075] The preparation method of the acne-removing liposomes includes the following steps:

[0076] (1) Mix the Magnolia officinalis bark extract, glycyrrhetinic acid, tau phenol, emulsifier, co-emulsifier, polyol and phospholipid, and stir at 65°C to form a homogeneous and clear mixture A.

[0077] (2) Mix nicotinamide, thyme extract and water, and stir at 65°C to form a homogeneous and clear mixture B;

[0078] (3) Pour mixture A into mixture B and mix well. Stir at 65°C to form a homogeneous mixture C.

[0079] (4) The mixture C was subjected to high pressure homogenization at 600 bar, 3 times, and cooled to room temperature to obtain the acne-removing liposome.

[0080] Example 4:

[0081] One embodiment of the acne-removing liposome of the present invention includes an acne-removing composition and a liposome carrier excipient.

[0082] The acne-removing liposome comprises the following components by weight percentage:

[0083] Nicotinamide 2%, Magnolia officinalis bark extract 1%, glycyrrhetinic acid 0.15%, tau tannin 0.1%, senna extract 0.01%, phospholipids 0.1%, emulsifier 10%, co-emulsifier 1%, polyol 10%, water to 100%.

[0084] The phospholipid is hydrogenated soybean lecithin;

[0085] The emulsifier comprises PEG-60 hydrogenated castor oil;

[0086] The co-emulsifier is PPG-26-butanol polyether-26;

[0087] The polyol is octyldodecyl alcohol.

[0088] The preparation method of the acne-removing liposomes includes the following steps:

[0089] (1) Mix the Magnolia officinalis bark extract, glycyrrhetinic acid, tau phenol, emulsifier, co-emulsifier, polyol and phospholipid, and stir at 45-65℃ to form a homogeneous and clear mixture A.

[0090] (2) Mix nicotinamide, thyme extract and water, and stir at 45°C to form a homogeneous and clear mixture B;

[0091] (3) Pour mixture A into mixture B and mix evenly. Stir at 45°C to form a homogeneous mixture C.

[0092] (4) The mixture C was subjected to high pressure homogenization at 500 bar, 3 times, and cooled to room temperature to obtain the acne-removing liposome.

[0093] Example 5:

[0094] One embodiment of the acne-removing liposome of the present invention includes an acne-removing composition and a liposome carrier excipient.

[0095] The acne-removing liposome comprises the following components by weight percentage:

[0096] Niacinamide 8%, Magnolia officinalis bark extract 5%, glycyrrhetinic acid 2.01%, tau tannin 2%, senna extract 0.09%, phospholipids 5%, emulsifier 30%, co-emulsifier 5%, polyol 40%, water to 100%.

[0097] The phospholipid is soybean lecithin;

[0098] The emulsifier contains 10% polyglycerol lauryl ester, 15% cocoyl glucoside, and 5% Tween 80;

[0099] The co-emulsifier is lauryl alcohol polyether-23;

[0100] The polyol comprises 10% 1,2-pentanediol, 20% glycerol, and 10% ethoxydiethylene glycol.

[0101] The preparation method of the acne-removing liposomes is the same as in Example 1.

[0102] Example 6:

[0103] One embodiment of the acne-removing liposome of the present invention includes an acne-removing composition and a liposome carrier excipient.

[0104] The acne-removing liposome comprises the following components by weight percentage:

[0105] Niacinamide 8%, Magnolia officinalis bark extract 5%, glycyrrhetinic acid 1.95%, tau tannin 2%, senna extract 0.15%, phospholipids 5%, emulsifier 30%, co-emulsifier 5%, polyol 40%, water to 100%.

[0106] The phospholipid is soybean lecithin;

[0107] The emulsifier contains 10% polyglycerol lauryl ester, 15% cocoyl glucoside, and 5% Tween 80;

[0108] The co-emulsifier is lauryl alcohol polyether-23;

[0109] The polyol comprises 10% 1,2-pentanediol, 20% glycerol, and 10% ethoxydiethylene glycol.

[0110] The preparation method of the acne-removing liposomes is the same as in Example 1.

[0111] Comparative Example 1:

[0112] This invention provides a comparative example of an acne-removing liposome. The only difference between this comparative example and Example 1 is that niacinamide is not added, and the liposome is made up with an equal amount of water. The other components are the same as in Example 1.

[0113] The preparation method of the acne-removing liposomes is the same as in Example 1.

[0114] Comparative Example 2:

[0115] This invention provides a comparative example of an acne-removing liposome. The only difference between this comparative example and Example 1 is that glycyrrhetinic acid is not added, and the amount of water is made up to the same level. The other components are the same as in Example 1.

[0116] The preparation method of the acne-removing liposomes is the same as in Example 1.

[0117] Comparative Example 3:

[0118] This invention provides a comparative example of an acne-removing liposome. The only difference between this comparative example and Example 1 is that no tau phenol is added, and the amount of water is made up to the required level. The other components are the same as in Example 1.

[0119] The preparation method of the acne-removing liposomes is the same as in Example 1.

[0120] Comparative Example 4:

[0121] This invention provides a comparative example of an acne-removing liposome. The only difference between this comparative example and Example 1 is that the acne-removing liposome does not contain Magnolia officinalis bark extract and is supplemented with an equal amount of water. The other components are the same as in Example 1.

[0122] The preparation method of the acne-removing liposomes is the same as in Example 1.

[0123] Comparative Example 5:

[0124] This invention provides a comparative example of an acne-removing liposome. The only difference between this comparative example and Example 1 is that the acne-removing liposome does not contain thyme extract and is made up with an equal amount of water. The other components are the same as in Example 1.

[0125] The preparation method of the acne-removing liposomes is the same as in Example 1.

[0126] Comparative Example 6:

[0127] A comparative example of the acne-removing liposomes of the present invention, wherein the acne-removing liposomes include an acne-removing composition and a liposome carrier excipient.

[0128] The acne-removing liposome comprises the following components by weight percentage:

[0129] Niacinamide 8.5%, Magnolia officinalis bark extract 5%, glycyrrhetinic acid 2%, tau tannin 1.5%, senna extract 0.1%, phospholipids 5%, emulsifier 30%, co-emulsifier 5%, polyol 40%, water to 100%.

[0130] The phospholipid is soybean lecithin;

[0131] The emulsifier contains 10% polyglycerol lauryl ester, 15% cocoyl glucoside, and 5% Tween 80;

[0132] The co-emulsifier is lauryl alcohol polyether-23;

[0133] The polyol comprises 10% 1,2-pentanediol, 20% glycerol, and 10% ethoxydiethylene glycol.

[0134] Comparative Example 7:

[0135] This invention provides a comparative example of an acne-removing liposome. The only difference between this comparative example and Example 1 is that the herb extract is replaced with an equal amount of rosemary extract, while the other components are the same as in Example 1.

[0136] The preparation method of the acne-removing liposomes is the same as in Example 1.

[0137] Comparative Example 8:

[0138] This comparative example provides a free composition comprising 8% nicotinamide, 5% magnolia bark extract, 2% glycyrrhetinic acid, 2% tau tannin, 0.1% senna extract, 8.29% dimethyl sulfoxide (DMSO), and 74.61% water.

[0139] The preparation method of the free composition includes the following steps:

[0140] The free composition was obtained by mixing Magnolia officinalis bark extract, glycyrrhetinic acid, tau tannin, nicotinamide, thymol extract, dimethyl sulfoxide, and water.

[0141] Test Example 1: Characterization Test and Stability Test

[0142] Test samples: Acne-removing liposomes from Examples 1-4 and Comparative Examples 1-7.

[0143] 1. Use an instrument (particle size analyzer) to detect the particle size and PDI of the test samples.

[0144] The electron micrograph of liposomes in Example 1 is shown below. Figure 1 As shown. Test results show that the average particle size of the acne-removing liposomes in Examples 1-4 and Comparative Examples 1-7 is less than 100 nm, and the PDI is 0.05-0.4. Specifically, the average particle size of the acne-removing liposomes in Example 1 is 24.68 nm, and the PDI is 0.091; the average particle size of the acne-removing liposomes in Example 2 is 26.87 nm, and the PDI is 0.108; the average particle size of the acne-removing liposomes in Example 3 is 28.36 nm, and the PDI is 0.065; the average particle size of the acne-removing liposomes in Example 4 is 29.21 nm, and the PDI is 0.072; the average particle size of the acne-removing liposomes in Example 5 is 28.16 nm, and the PDI is 0.165; and the average particle size of the acne-removing liposomes in Example 6 is 29.52 nm, and the PDI is 0.105.

[0145] The average particle size of the acne-removing liposomes in Comparative Example 1 was 36.18 nm, and the PDI was 0.121; the average particle size of the acne-removing liposomes in Comparative Example 2 was 32.19 nm, and the PDI was 0.216; the average particle size of the acne-removing liposomes in Comparative Example 3 was 30.12 nm, and the PDI was 0.186; the average particle size of the acne-removing liposomes in Comparative Example 4 was 30.31 nm, and the PDI was 0.216; the average particle size of the acne-removing liposomes in Comparative Example 5 was 32.65 nm, and the PDI was 0.106; the average particle size of the acne-removing liposomes in Comparative Example 6 was 31.62 nm, and the PDI was 0.296; and the average particle size of the acne-removing liposomes in Comparative Example 7 was 33.82 nm, and the PDI was 0.183.

[0146] 2. The acne-removing liposomes of Examples 1-4 and Comparative Examples 1-7 were placed in sealed containers and placed at -20℃, room temperature, 4℃ and 45℃ for 3 months respectively to observe their stability changes.

[0147] The results showed that none of the acne-removing liposome samples exhibited stratification or precipitation, and the particle size did not change significantly, indicating that the acne-removing liposomes prepared in this invention have good stability.

[0148] Test Example 2: Evaluation of Irritation of Chicken Embryo Allantoic Membrane

[0149] The acne-removing liposomes from Examples 1-4 were diluted 10 times with water, and 200 μL of the diluted acne-removing liposomes were dropped onto the surface of the chicken embryo allantoic membrane. After waiting for 300 seconds, vascular changes were observed, and CAM vascular changes were observed within 5 minutes. The initial time of CAM vascular congestion, hemorrhage, and coagulation was recorded. The irritation score (IS) was calculated according to formula (1):

[0150] IS=[(301-secH)×5+(301-secL)×7+(301-secC)×9] / 300——Equation (1)

[0151] In the above formula, secH is the initial time of surface congestion, s; secL is the initial time of surface bleeding, s; and secC is the initial time of surface clotting, s.

[0152] Calculate the mean of the repeated test results, and classify the irritation level of the test substance according to the magnitude of the mean. Among them, 0~0.9, 1.0~4.9, 5.0~8.9 and 9~21.0 are classified as no irritation, mild irritation, moderate irritation and severe irritation, respectively.

[0153] Test results show that after the acne-removing liposomes were diluted 10 times with water and contacted with the chicken embryo allantoic membrane for 300 seconds, there was no bleeding, vascular dissolution, or coagulation in the capillaries. The reaction scores of Examples 1-4 were 0.05, 0.07, 0.06, and 0.07, respectively, indicating that the acne-removing liposomes prepared by this invention have good safety and are non-irritating.

[0154] Test Example 3: Patch Test

[0155] Thirty subjects were selected. Both 10% of the acne-removing liposomes described in Examples 1-4 and a blank control were applied to the flexor aspect of the subjects' forearms for 24 hours. After removing the applicator, the skin reaction was observed after a 30-minute interval, once the indentation disappeared. Skin reactions were observed again 24 hours and 48 hours after removing the applicator.

[0156] The results showed that none of the 30 subjects experienced symptoms such as light redness, erythema, edematous erythema, significant redness and swelling, infiltration or papules, or papules or vesicles, indicating that the acne-removing liposomes prepared in Examples 1-4 were non-irritating to human skin.

[0157] Test Example 4: Determination of skin cumulative permeation and skin retention

[0158] Transdermal assays of isolated porcine skin were performed using the Franz diffusion cell method. The acne-removing liposome from Example 1 and the free composition from Comparative Example 8 were diluted to a 5% dilution. 0.5 g of each was placed in the supply chamber, using PBS (pH 7.4) as the receiving solution. HPLC analysis was performed to calculate the cumulative permeation per unit area of ​​the active ingredient (tocopherol / nicotinamide) at different time points. After 24 h, the supernatant of the skin homogenate was analyzed by HPLC to calculate the skin retention per unit area of ​​the active ingredient. The cumulative permeation per unit area of ​​the active ingredient at different sampling times was calculated according to formula (2).

[0159] —Equation (2)

[0160] In the above formula, Qn is the cumulative drug permeation, Cn is the drug concentration measured at the nth time, Ci is the drug concentration measured at the ith point, V0 is the volume of the diffusion cell (i.e., the amount of release medium added), and Vi is the sampling amount each time. The cumulative permeation per unit area is Q = Qn / S, where S is the area of ​​the diffusion cell (2.27 cm²). 2 .

[0161] Table 1

[0162]

[0163] The results are shown in Table 1. The cumulative skin permeation of tau phenol per unit area over 12 h in the free composition and the acne-reducing liposomes was 12.48 μg / cm². 2 and 28.16 μg / cm 2 The cumulative skin permeability per unit area over 24 hours was 30.47 μg / cm³. 2 and 69.20 μg / cm 2 The skin retention amount was 40.39 μg / cm³. 2 and 98.49 μg / cm 2 Compared with free tau phenol, the cumulative skin permeation of tau phenol per unit area in acne-removing liposomes increased by 125.64% and 127.11% at 12 h and 24 h, respectively, and the skin retention increased by 143.85%.

[0164] The cumulative skin permeation of niacinamide per unit area over 12 hours in the free composition and in the acne-fighting liposomes was 72.12 μg / cm². 2 and 92.59 μg / cm 2 The cumulative skin permeability per unit area over 24 hours was 178.18 μg / cm³. 2 and 316.84 μg / cm 2 The skin retention amount was 21.41 μg / cm³. 2 and 86.78 μg / cm 2Compared with free niacinamide, the cumulative skin permeation of niacinamide per unit area in acne-fighting liposomes increased by 28.38% and 77.86% at 12h and 24h, respectively, while the skin retention increased by 305.32%. This indicates that encapsulation of active ingredients in liposomes can effectively promote transdermal absorption and skin retention, thereby improving their skin bioavailability.

[0165] Test Example 5: The effect of acne-reducing liposomes on the release of inflammatory factors

[0166] Raw 264.7 cells cultured to the exponential growth phase in DMEM medium containing 10% FBS and 1% PS were injected at 1×10⁻⁶ cells / year. 5 Cells were seeded at 500 μL / mL in 24-well plates. After culturing for 3 h, 0.5 mL of acne-removing liposomes prepared by Comparative Examples 1-8 and Examples 1, 5, and 6 (with the same dilution factor) diluted 2000 times were added to each experimental group (Comparative Example 8 was a free composition). After culturing for 15 h, except for the blank control group, 4 mg / L of LPS was added to each group of cells to prepare a cell inflammation model, and the cells were incubated at 37°C for another 6 h.

[0167] The supernatant culture medium was collected, and the expression levels of IL-1β, IL-6h, and IL-8 were detected according to the ELISA kit instructions. The results are shown in Table 2.

[0168] Table 2 Results of inflammatory factor release tests in each group (n=3)

[0169]

[0170] Note: ## indicates comparison with blank control, p<0.01; ** indicates comparison with model, p<0.01; a indicates comparison with comparative examples 1-5, p<0.01; b indicates comparison with comparative example 6, p<0.01; c indicates comparison with comparative example 7, p<0.01; d indicates comparison with comparative example 8, p<0.01; e indicates comparison with examples 5 and 6, p<0.01.

[0171] The experimental results in Table 2 show that, compared with the blank control group, the secretion of IL-1β, IL-6 and IL-8 in the model group increased significantly after the addition of LPS (p<0.01); compared with the model group, the acne-removing liposome / free compositions prepared in Examples 1, 4, 5 and Comparative Examples 1-8 can significantly reduce the secretion of IL-1β, IL-6 and IL-8 (p<0.01).

[0172] Compared with Comparative Examples 1-5, the acne-removing liposome of Example 1 encapsulates five active ingredients: nicotinamide, glycyrrhetinic acid, tau syrup, magnolia bark extract, and sage extract. Its effect of inhibiting the secretion of IL-1β, IL-6, and IL-8 by Raw 264.7 cells is better than that of the acne-removing liposomes obtained by combining any four active ingredients (p<0.01).

[0173] Compared with Comparative Example 6, the weight ratios of nicotinamide, glycyrrhetinic acid, tau tannin, magnolia bark extract, and senna extract in Comparative Example 6 were not within the scope of this invention, resulting in a decrease in the effect of inhibiting the secretion of IL-1β, IL-6, and IL-8 by Raw 264.7 cells, and thus failing to achieve the best effect.

[0174] Compared to Comparative Example 7, Example 1 showed a decrease in the effectiveness of the acne-reducing liposome in inhibiting the secretion of IL-1β, IL-6, and IL-8 by Raw 264.7 cells after replacing the senna extract with rosemary extract. This indicates that replacing any component in the acne-reducing composition of the present invention will affect the anti-inflammatory effect. The reason for this is that the senna extract contains monoterpenoids such as pinone and isopinone, as well as rosmarinic acid and pinone derivatives. When combined with nicotinamide, glycyrrhetinic acid, tau salsa, and magnolia bark extract, it can reduce the release of inflammatory factors by directly inhibiting the NF-κB or MAPK signaling pathway. However, after replacing it with rosemary extract, which mainly contains caryopsisic acid, caryopsisol, and rosmarinic acid, its anti-inflammatory mechanism depends on the Nrf2 / ARE pathway (antioxidant pathway), inhibiting NF-κB, and has a weaker effect on IL-6 and IL-8.

[0175] Compared with Examples 5 and 6, the results of Example 1 showed that when the mass ratio of glycyrrhetinic acid to senna extract was (15-20):1, the anti-inflammatory effect was more significant and superior to other mass ratios. When glycyrrhetinic acid and senna extract were combined at this specific mass ratio, the glucocorticoid-like effect of glycyrrhetinic acid and the direct pathway inhibition of senna formed a dual regulatory effect, covering the upstream and downstream of the inflammatory response (e.g., glycyrrhetinic acid inhibits transcription factors, while senna blocks signal transduction), optimizing the bioavailability of the two active ingredients and avoiding competitive inhibition caused by excessive amounts of one ingredient (e.g., excessively high concentrations of glycyrrhetinic acid may inhibit the effects of certain terpenes in senna).

[0176] Compared with the free composition of Comparative Example 8, the acne-reducing liposomes prepared in Example 1 showed a more significant effect in inhibiting the secretion of IL-1β, IL-6 and IL-8 by Raw 264.7 cells (p<0.01). The anti-inflammatory efficacy of the encapsulated acne-reducing composition was superior to that of the free composition at the same dose.

[0177] Test Example 6: Effect of Acne-Clearing Liposomes on Antibacterial Activity

[0178] Using an inoculation loop, pick up a small amount of *Propionibacterium acnes* (ATCC6919) and *Staphylococcus aureus* from the surface of the activated culture medium. Add sterile saline solution and use a sterile pipette to vigorously pipette and disperse the bacteria evenly in the saline solution. Adjust the bacterial concentration to a 0.5 McFarland turbidity tube (1.5 × 10⁻⁶). 8 Similar to CFU / mL. After fixation, circular filter paper discs (d=6 mm) were attached to the surface of the culture medium, and 5 μL of the acne-reducing liposomes prepared in Comparative Examples 1-8 and Examples 1, 5, and 6 (Comparative Example 8 was a free composition) were vertically added onto the filter paper discs. The petri dishes with the drug sensitivity paper discs attached were placed in an incubator at 37°C and incubated overnight. After incubation, the plates were removed, and the diameter of the inhibition zone was measured with calipers. The edge of the inhibition zone was limited to the point where no obvious bacterial growth was visible to the naked eye. The results were recorded. The results are shown in Table 3.

[0179] Table 3. Determination of inhibition zone size using the paper disc diffusion method (n=3)

[0180]

[0181] Note: ## indicates comparison with Comparative Examples 1-5, p<0.01; ** indicates comparison with Comparative Example 7, p<0.01; @@ indicates comparison with Comparative Example 8, p<0.01; && indicates comparison with Examples 5 and 6, p<0.01.

[0182] As shown in Table 3, after adding 5 μL of different test group samples to a 6 mm paper, compared with Comparative Examples 1-5, the average diameter of the inhibition zone of Propionibacterium acnes and Staphylococcus aureus in Example 1 increased more significantly, indicating that the liposomes prepared by combining five active ingredients, namely nicotinamide, glycyrrhetinic acid, tau tannin, Magnolia officinalis bark extract, and senna extract, have a synergistic effect.

[0183] Compared with Comparative Example 6, the weight ratios of nicotinamide, glycyrrhetinic acid, tau tannin, magnolia bark extract, and sage extract in Comparative Example 6 are not within the scope of this invention, resulting in a decrease in antibacterial effect and failure to achieve the best effect.

[0184] Compared to Comparative Example 7, Example 1 showed a decrease in the antibacterial efficacy against Propionibacterium acnes and Staphylococcus aureus in the acne-removing liposomes of Comparative Example 7, where the sage extract was replaced with rosemary extract. This demonstrates that replacing any component in the acne-removing composition of the present invention affects the antibacterial efficacy. This is because the main active ingredients of rosemary extract include caryopsisic acid and caryopsisol, while the main active ingredients of sage extract include pinone and isopinone. Sage extract contains unique and highly effective membrane-disrupting components (such as pinone), exhibiting significant anti-inflammatory, antioxidant, antibacterial, and skin barrier repair effects. While rosemary extract possesses certain anti-inflammatory effects, it is weaker in regulating sebum secretion, inhibiting Propionibacterium acnes, or promoting keratinocyte metabolism, resulting in a failure to achieve optimal antibacterial efficacy when combined with other components.

[0185] Compared with Examples 5 and 6, the results of Example 1 showed that when the mass ratio of glycyrrhetinic acid to senna extract was (15-20):1, the inhibitory effect on Propionibacterium acnes and Staphylococcus aureus was superior to other mass ratios. At this specific mass ratio, the combination of glycyrrhetinic acid and senna extract allowed glycyrrhetinic acid to inhibit the NF-κB pathway, reducing neutrophil infiltration and indirectly lowering the bacterial survival environment (changes in pH and nutrient supply at the inflammatory site). Senna extract could scavenge ROS, preventing bacteria from activating virulence genes (such as the agr quorum sensing system of Staphylococcus aureus) using oxidative stress. Glycyrrhetinic acid preferentially controlled inflammation, while senna extract assisted in direct bactericidal action, avoiding excessive inflammation leading to antibacterial resistance (such as the tolerance phenotype of Staphylococcus aureus), thereby significantly improving the antibacterial effect.

[0186] Compared with the free composition of Comparative Example 8, the acne-removing liposomes prepared in Example 1 showed better inhibitory effects on Propionibacterium acnes and Staphylococcus aureus than the free composition at the same dosage.

[0187] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. An anti-acne liposome, characterized by, The acne-removing liposome comprises the following components in mass percentage: nicotinamide 2-8%, Magnolia officinalis bark extract 1-5%, glycyrrhizinic acid 0.15-2%, persicin 0.1-2%, Hyptis suaveolens extract 0.01-0.1%, phospholipid 0.1-5%, emulsifier 10-30%, co-emulsifier 1-5%, polyhydric alcohol 10-40%, and the balance of water; the mass ratio of glycyrrhizinic acid to Hyptis suaveolens extract is glycyrrhizinic acid: Hyptis suaveolens extract = (15-20):

1.

2. The liposome of claim 1, wherein the liposome is a liposome comprising a combination of a phospholipid and a non-ionic surfactant. The phospholipid comprises at least one of soybean lecithin, hydrogenated lecithin, and egg yolk lecithin; And / or, the emulsifier comprises at least one of polyoxyethylene castor oil emulsifier, polyoxyethylene hydrogenated castor oil emulsifier, polyglycerol emulsifier, poloxamer, cocoglycoside, triglyceride, pyrrolidone, Tween 80, Tween 20, and Tween 60; And / or, the co-emulsifier comprises at least one of laureth-23, diethylene glycol monoethyl ether, PPG-26-butanol polyether-26, trideceth-12; And / or, the polyhydric alcohol comprises at least one of glycerol, propylene glycol, 1,2-pentanediol, ethoxydiglycol, 1,2-hexanediol, dipropylene glycol, isopropyl alcohol, polyethylene glycol-200, octyldodecanol, and butanediol.

3. The method for preparing acne-removing liposomes as described in claim 1 or 2, characterized in that, The method comprises the following steps: (1) mixing Magnolia officinalis bark extract, glycyrrhizinic acid, persicin, emulsifier, co-emulsifier, polyhydric alcohol, and phospholipid to obtain a mixed solution A; (2) mixing nicotinamide, Hyptis suaveolens extract, and water to obtain a mixed solution B; (3) mixing the mixed solution A into the mixed solution B to obtain a mixed solution C; (4) performing nanofication treatment on the mixed solution C to obtain the acne-removing liposome.

4. The production method according to claim 3, wherein The nanofication treatment comprises extrusion, ultrasonic treatment, or homogenization.

5. The production method according to claim 4, wherein The homogenization is performed at 500-1000 bar.

6. Use of the acne-removing liposome of claim 1 or 2 in the preparation of an acne-removing product.

7. An anti-acne product, characterized in that, The acne-removing product comprises the acne-removing liposome of claim 1 or 2.

Images