Acne-removing composition, liposome and preparation method and application thereof

Abstract

The invention relates to the technical field of cosmetics, in particular to an acne-removing composition, lipidosome and a preparation method and application thereof. The acne-removing composition disclosed by the invention is prepared from the following components in parts by weight: 2 to 8 parts of nicotinamide, 1 to 5 parts of cortex magnoliae officinalis extract, 0.15 to 2.01 parts of glycyrrhizic acid, 0.1 to 2 parts of totarol and 0.01 to 0.15 part of hyssopus officinalis extract. The nano-carrier is adopted to wrap and deliver the acne removal composition, so that the solubility of the functional components is increased, the bioavailability of the functional components is improved, meanwhile, the irritation of the functional components is also improved, multi-target co-delivery and multi-mechanism acne removal are realized, and the acne removal composition has a remarkable acne removal effect.

Description

TECHNICAL FIELD

[0001] The present application relates to the cosmetic technology field, and in particular to a kind of acne-removing composition, liposome and its preparation method and application. BACKGROUND

[0002] Acne is a chronic inflammatory skin disease involving follicular sebaceous units, often occurs on the cheeks, back and chest; It can occur in people of all ages, with the highest incidence in adolescents.

[0003] The pathogenesis of acne is complex, and the mainstream view believes that it is related to the following four aspects: excessive lipid secretion under the action of androgen, keratinization abnormalities of follicular sebaceous duct (pimple formation), massive proliferation of follicular microorganisms, inflammation and immune response.

[0004] The mechanism of skin acne removal is complex, although there are many types of acne-removing skin care products on the market, but the acne-removing mechanism is single, most products use acid brushing to achieve acne-removing effect, but it is easy to cause excessive cleaning and damage to the skin barrier. Many active ingredients with acne-removing effect, such as vitamins and their derivatives, polypeptide active substances, are sensitive to enzymes, light, heat, pH value, etc. They have strong irritation, poor stability, are easy to degrade and inactivate, and have poor transdermal absorption. Direct application in cosmetic products can lead to oxidation and inactivation, thereby affecting the skin care effect at the target site. The stratum corneum of the skin has strong keratinocyte barrier function, and active molecules are difficult to penetrate the stratum corneum, ultimately resulting in a significant reduction in acne-removing effect. SUMMARY

[0005] The purpose of the present application is to overcome the deficiencies in the prior art and provide an acne-removing composition and liposome that can co-deliver multiple targets and have multiple acne-removing mechanisms, with significant acne-removing effect.

[0006] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows: In a first aspect, the present application provides an acne-removing composition comprising the following components by weight: nicotinamide 2-8 parts, Magnolia officinalis bark extract 1-5 parts, glycyrrhizic acid 0.15-2.01 parts, persicin 0.1-2 parts and Hyptis suaveolens extract 0.01-0.15 parts.

[0007] The present application considers multiple acne-removing mechanisms and combines nicotinamide, Magnolia officinalis bark extract, glycyrrhizic acid, persicin and Hyptis suaveolens extract to obtain an acne-removing composition (the present application names it ACNITECH): Nicotinamide promotes skin metabolism, removes excess keratin, controls sebum secretion, inhibits melanin transfer, lightens acne marks and evens out skin tone.

[0008] In the present application, magnolia bark extract: has the effects of anti-inflammatory and antioxidant, etc., can effectively inhibit the overgrowth of pathogenic bacteria such as propionibacterium acnes.

[0009] In the present application, glycyrrhizinic acid: a high-activity anti-inflammatory ingredient, inhibits the production of inflammatory factors, reduces skin inflammation, and improves skin immunity.

[0010] In the present application, kaempferol: can inhibit propionibacterium acnes, reduce inflammation, help improve acne and comedones; regulate sebum secretion, suitable for oily and mixed skin, help keep skin clean; anti-inflammatory and repair effect, suitable for sensitive skin, can relieve redness and irritation.

[0011] In the present application, hyssop extract: has antibacterial and anti-inflammatory effects, can help prevent and improve skin problems such as acne, relieve skin inflammation and redness; has soothing and repairing effects, suitable for sensitive skin, can relieve skin irritation and discomfort; has certain astringent effect, helps shrink pores and improve skin texture. The above functional ingredients are scientifically and reasonably matched within the scope of the present application, target the following pathways to regulate and intervene the skin: increased sebum secretion and component change; excessive keratinization of hair follicle keratin layer; increased reproduction of propionibacterium acnes in hair follicle sebaceous glands and biofilm formation; skin inflammatory response; inhibition of nerve hyper-reflex; change of skin microecological environment, with significant acne-removing effect.

[0012] Preferably, the mass ratio of glycyrrhizinic acid and hyssop extract is glycyrrhizinic acid:hyssop extract= (15-20):1.

[0013] The present application has found that, through a large number of researches, glycyrrhizinic acid and hyssop extract are compounded in a specific ratio, the glucocorticoid-like effect of glycyrrhizinic acid and the direct pathway inhibition of hyssop form a double regulation, covering the upstream and downstream of the inflammatory response (such as the inhibition of transcription factors by glycyrrhizinic acid and the blocking of signal transduction by hyssop), which can better improve the bioavailability of the two components and exert the best anti-inflammatory and acne-removing effects. If a component is excessive, it may cause competitive inhibition: for example, high concentration of glycyrrhizinic acid may inhibit the effect of some terpenes in hyssop, resulting in decreased effect.

[0014] In the second aspect, the present application provides an acne-removing liposome, which comprises the above-mentioned acne-removing composition and a liposome carrier auxiliary material; the liposome carrier auxiliary material comprises phospholipids, emulsifiers, co-emulsifiers, polyols and water.

[0015] Nano-liposomes generally refer to small single-chamber liposomes with a particle size of less than 100 nm, which can encapsulate water-soluble or fat-soluble active substances, have the advantages of sustained release, biodegradability, no immunogenicity and toxicity, etc. The nano-level size and good deformability enable them to have strong ability to penetrate physiological tissue barriers. Nano-carriers used in cosmetics can significantly improve the skin penetration ability of active ingredients.

[0016] The present application delivers the scientifically matched acne-removing composition by a new nano-technology with a nano-carrier. Based on the nano-carrier structure and characteristics, the nano-wrapped acne-removing composition has good stability and water dispersibility, increases the solubility of the effective components, and improves the irritation of the effective components. The transdermal delivery can achieve sustained release, long-acting, multi-target effect, and significantly improve the efficacy.

[0017] Preferably, the average particle size of the acne-removing liposome is 24.68 nm-29.52 nm.

[0018] Preferably, the acne-removing liposome comprises the following components in mass percentage: acne-removing composition 3.26-17.1%, phospholipid 0.1-5%, emulsifier 10-30%, co-emulsifier 1-5%, polyol 10-40%, and the balance is water.

[0019] Preferably, the phospholipid comprises at least one of soybean lecithin, hydrogenated lecithin, egg yolk lecithin, hydrogenated soybean lecithin, and hydrogenated egg yolk lecithin.

[0020] Preferably, the emulsifier comprises at least one of polyoxyethylene castor oil emulsifier, polyoxyethylene hydrogenated castor oil emulsifier, polyglycerol emulsifier, poloxamer, cocoglycoside, triglyceride, pyrrolidone, polyglyceryl acid ester, polyglyceryl lactic acid ester, polyglyceryl stearate, polyglyceryl capryl / capryl acid ester, polyglyceryl laurate, Tween 80, Tween 20, Tween 60, PEG-20 hydrogenated castor oil, PEG-40 hydrogenated castor oil, and PEG-60 hydrogenated castor oil.

[0021] Preferably, the co-emulsifier comprises at least one of lauryl polyether-23, diethylene glycol monoethyl ether, PPG-26-butanol polyether-26, tridecyl alcohol polyether-12.

[0022] Preferably, the polyol comprises at least one of glycerol, propylene glycol, 1,3-butanediol, 2,3-butanediol, 1,3-propanediol, 1,2-pentanediol, ethoxydiglycol, 1,2-hexanediol, dipropylene glycol, isopropyl alcohol, polyethylene glycol-200, PPG-10 sorbitol, octyldodecanol, and butanediol.

[0023] In a third aspect, the present application provides a preparation method of the acne-removing liposome, comprising the following steps: (1) mixing magnolia bark extract, glycyrrhizic acid, persic acid, emulsifier, co-emulsifier, polyol, and phospholipid to obtain a mixed solution A; (2) mixing nicotinamide and sage extract with water to obtain a mixed solution B; (3) Pouring the mixed solution A into the mixed solution B and mixing evenly to obtain a mixed solution C; (4) Carrying out nano-treatment on the mixed solution C to obtain the acne-removing liposome.

[0024] Preferably, the nano-treatment comprises extrusion, ultrasonic or homogenization.

[0025] Preferably, the homogenization is carried out at 500-1000 bar.

[0026] Preferably, the mixing of the steps (1)-(3) is carried out at 45-65℃ under stirring.

[0027] In a fourth aspect, the present application provides use of the acne-removing composition or the acne-removing liposome in an acne-removing product.

[0028] The acne-removing liposome obtained by the present application is used in the preparation of an acne-removing product, and the efficacy components are delivered by the liposome, so that the efficacy product can reach a sufficient concentration to exert corresponding functional effects. The solubility of each efficacy component is effectively improved, and a stable storage space is provided for the efficacy component, so that unnecessary degradation or inactivation of the efficacy component during storage and before use is avoided, which is beneficial to improving the concentration of the efficacy component in the acne-removing product.

[0029] In a fifth aspect, the present application provides an acne-removing product comprising the acne-removing composition or the acne-removing liposome.

[0030] The present application has the following advantages: The present application considers multiple acne-removing mechanisms and combines niacinamide, magnolia bark extract, glycyrrhizic acid, persicin, and hyssop extract to obtain an acne-removing composition. The efficacy components are scientifically and reasonably matched, and target the following pathways to regulate and intervene the skin: increased sebum secretion and component change; excessive keratinization of the hair follicle keratin layer; increased amount of Propionibacterium acnes in the hair follicle sebaceous gland and biofilm formation; skin inflammatory response; inhibition of neurogenic inflammation; and change of the skin microecological environment, which has a significant acne-removing effect.

[0031] The present application uses a nano-carrier to encapsulate and deliver the acne-removing composition matched scientifically by a new nano technology. Based on the structure and characteristics of the nano-carrier, an acne-removing liposome is obtained by nano-encapsulation, which has good stability and water dispersibility, increases the solubility of the efficacy components, and also improves the irritability of the efficacy components, so that the efficacy components can reach a sufficient concentration in the product to exert corresponding functional effects. The solubility of each efficacy component is effectively improved, and a stable storage space is provided for the efficacy component, so that unnecessary degradation or inactivation of the efficacy component during storage and before use is avoided, which is beneficial to improving the concentration of the efficacy component in the acne-removing product. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1The electron microscope image of the anti-acne liposome prepared in the application. DETAILED DESCRIPTION

[0033] For the purpose of better illustrating the technical scheme, advantages and merits of the present application, the present application will be further described in conjunction with specific examples.

[0034] The Magnolia officinalis bark extract and the Hyptis suaveolens extract used in the present application are purchased from Xi'an Shilin Technology Co., Ltd. It is found in the experimental exploration of the present application that the extraction method does not affect the efficacy exertion.

[0035] Example 1 An embodiment of the anti-acne liposome described in the present application comprises an anti-acne composition and a liposome carrier auxiliary material.

[0036] The anti-acne liposome comprises the following components in mass percentage: Nicotinamide 8%, Magnolia officinalis bark extract 5%, glycyrrhizic acid 2%, persicin 2%, Hyptis suaveolens extract 0.1%, phospholipid 5%, emulsifier 30%, co-emulsifier 5%, polyol 40%, and water to make up to 100%.

[0037] The phospholipid is soybean lecithin; The emulsifier comprises 10% polyglyceryl laurate, 15% coco-glucoside, and 5% Tween 80; The co-emulsifier is laureth-23; The polyol comprises 10% 1,2 pentanediol, 20% glycerol, and 10% ethoxydiglycol.

[0038] The preparation method of the anti-acne liposome comprises the following steps: (1) uniformly mix Magnolia officinalis bark extract, glycyrrhizic acid, persicin, emulsifier, co-emulsifier, polyol, and phospholipid, and stir at 45℃ to form a uniform and clear mixed solution A; (2) uniformly mix nicotinamide, Hyptis suaveolens extract, and water, and stir at 45℃ to form a uniform and clear mixed solution B; (3) mix the mixed solution A into the mixed solution B uniformly, and stir at 45℃ to form a uniform mixed solution C; (4) perform high-pressure homogenization treatment on the mixed solution C at 1000 bar, circulate 3 times, and cool to room temperature to obtain the anti-acne liposome.

[0039] Example 2 An embodiment of the anti-acne liposome described in the present application comprises an anti-acne composition and a liposome carrier auxiliary material.

[0040] The anti-acne liposome comprises the following components in mass percentage: Nicotinamide 5%, Magnolia Bark Extract 3%, Glycyrrhizic Acid 1%, Quercetin 1%, Hyssop Extract 0.06%, Phospholipid 3%, Emulsifier 20%, Co-Emulsifier 3%, Polyol 30%, Water to 100%.

[0041] The phospholipid is hydrogenated lecithin; The emulsifier comprises 5% Tween 80, 10% coco-glucoside, 5% poloxamer; The co-emulsifier is PPG-26-butanol polyether-26; The polyol comprises 10% 1,2-hexanediol, 20% 1,3-propanediol.

[0042] The preparation method of the acne-removing liposome comprises the following steps: (1) uniformly mix Magnolia Bark Extract, Glycyrrhizic Acid, Quercetin, emulsifier, co-emulsifier, polyol, and phospholipid, and stir at 50°C to form a uniform and clear mixed solution A; (2) uniformly mix Nicotinamide, Hyssop Extract, and water, and stir at 50°C to form a uniform and clear mixed solution B; (3) mix the mixed solution A into the mixed solution B, and stir at 50°C to form a uniform mixed solution C; (4) perform high-pressure homogenization treatment on the mixed solution C at 800 bar, circulate 3 times, and cool to room temperature to obtain the acne-removing liposome.

[0043] Example 3: An embodiment of the acne-removing liposome comprises an acne-removing composition and a liposome carrier auxiliary material.

[0044] The acne-removing liposome comprises the following components in mass percentage: Nicotinamide 3%, Magnolia Bark Extract 2%, Glycyrrhizic Acid 0.5%, Quercetin 0.8%, Hyssop Extract 0.03%, Phospholipid 1%, Emulsifier 15%, Co-Emulsifier 2%, Polyol 20%, Water to 100%.

[0045] The phospholipid is hydrogenated soybean lecithin; The emulsifier comprises 10% PEG-20 hydrogenated castor oil, 5% Tween 20; The co-emulsifier is diethylene glycol monoethyl ether; The polyol comprises 10% 1,2-hexanediol, 10% isopropyl alcohol.

[0046] The preparation method of the acne-removing liposome comprises the following steps: (1) uniformly mix Magnolia Bark Extract, Glycyrrhizic Acid, Quercetin, emulsifier, co-emulsifier, polyol, and phospholipid, and stir at 65°C to form a uniform and clear mixed solution A; (2) Mix nicotinamide, extract of hyptis suaveolens and water uniformly, and stir at 65°C to form a uniform and clear mixed solution B; (3) Pour the mixed solution A into the mixed solution B and mix uniformly, and stir at 65°C to form a uniform mixed solution C; (4) Perform high-pressure homogenization treatment on the mixed solution C at 600 bar for 3 cycles, and cool to room temperature to obtain the acne-removing liposome.

[0047] Example 4: An embodiment of the acne-removing liposome comprises an acne-removing composition and a liposome carrier adjuvant.

[0048] The acne-removing liposome comprises the following components in mass percentage: nicotinamide 2%, magnolia bark extract 1%, glycyrrhizic acid 0.15%, persicin 0.1%, extract of hyptis suaveolens 0.01%, phospholipid 0.1%, emulsifier 10%, co-emulsifier 1%, polyol 10%, and water to make up to 100%.

[0049] The phospholipid is hydrogenated soybean lecithin; The emulsifier comprises PEG-60 hydrogenated castor oil; The co-emulsifier is PPG-26-butanol polyether-26; The polyol is octyldodecanol.

[0050] The preparation method of the acne-removing liposome comprises the following steps: (1) Mix magnolia bark extract, glycyrrhizic acid, persicin, emulsifier, co-emulsifier, polyol and phospholipid uniformly, and stir at 45-65°C to form a uniform and clear mixed solution A; (2) Mix nicotinamide, extract of hyptis suaveolens and water uniformly, and stir at 45°C to form a uniform and clear mixed solution B; (3) Pour the mixed solution A into the mixed solution B and mix uniformly, and stir at 45°C to form a uniform mixed solution C; (4) Perform high-pressure homogenization treatment on the mixed solution C at 500 bar for 3 cycles, and cool to room temperature to obtain the acne-removing liposome.

[0051] Example 5: An embodiment of the acne-removing liposome comprises an acne-removing composition and a liposome carrier adjuvant.

[0052] The acne-removing liposome comprises the following components in mass percentage: nicotinamide 8%, magnolia bark extract 5%, glycyrrhizic acid 2.01%, persicin 2%, extract of hyptis suaveolens 0.09%, phospholipid 5%, emulsifier 30%, co-emulsifier 5%, polyol 40%, and water to make up to 100%.

[0053] The phospholipid is soy lecithin; The emulsifier comprises 10% polyglyceryl laurate, 15% coco-glucoside, 5% Tween 80; The co-emulsifier is laureth-23; The polyol comprises 10% 1,2 pentanediol, 20% glycerin, 10% ethoxydiglycol.

[0054] The preparation method of the anti-acne liposome is the same as that of Example 1.

[0055] Example 6: In one embodiment of the anti-acne liposome, the anti-acne liposome comprises an anti-acne composition and a liposome carrier adjuvant.

[0056] The anti-acne liposome comprises the following components in mass percentage: Nicotinamide 8%, Magnolia Bark Extract 5%, Glycyrrhizinic Acid 1.95%, Persicin 2%, Hyssop Extract 0.15%, Phospholipid 5%, Emulsifier 30%, Co-emulsifier 5%, Polyol 40%, and water to make up to 100%.

[0057] The phospholipid is soy lecithin; The emulsifier comprises 10% polyglyceryl laurate, 15% coco-glucoside, 5% Tween 80; The co-emulsifier is laureth-23; The polyol comprises 10% 1,2 pentanediol, 20% glycerin, 10% ethoxydiglycol.

[0058] The preparation method of the anti-acne liposome is the same as that of Example 1.

[0059] Comparative Example 1: In one comparative example of the anti-acne liposome, the anti-acne liposome of the comparative example is different from Example 1 only in that no nicotinamide is added, and the rest of the components are the same as those of Example 1.

[0060] The preparation method of the anti-acne liposome is the same as that of Example 1.

[0061] Comparative Example 2: In one comparative example of the anti-acne liposome, the anti-acne liposome of the comparative example is different from Example 1 only in that no glycyrrhizinic acid is added, and the rest of the components are the same as those of Example 1.

[0062] The preparation method of the anti-acne liposome is the same as that of Example 1.

[0063] Comparative Example 3: A comparative example of the anti-acne liposome of the present application, the anti-acne liposome of the comparative example differs from example 1 only in that magnolol is not added, and is made up to the same amount with water, and the rest of the components are the same as example 1.

[0064] The preparation method of the anti-acne liposome is the same as example 1.

[0065] Comparative example 4: A comparative example of the anti-acne liposome of the present application, the anti-acne liposome of the comparative example differs from example 1 only in that magnolol is not added, and is made up to the same amount with water, and the rest of the components are the same as example 1.

[0066] The preparation method of the anti-acne liposome is the same as example 1.

[0067] Comparative example 5: A comparative example of the anti-acne liposome of the present application, the anti-acne liposome of the comparative example differs from example 1 only in that magnolol is not added, and is made up to the same amount with water, and the rest of the components are the same as example 1.

[0068] The preparation method of the anti-acne liposome is the same as example 1.

[0069] Comparative example 6: A comparative example of the anti-acne liposome of the present application, the anti-acne liposome includes an anti-acne composition and a liposome carrier auxiliary material.

[0070] The anti-acne liposome includes the following components in mass percentage: Nicotinamide 8.5%, magnolia bark extract 5%, glycyrrhizinic acid 2%, magnolol 1.5%, hyssop extract 0.1%, phospholipid 5%, emulsifier 30%, co-emulsifier 5%, polyol 40%, water to make up to 100%.

[0071] The phospholipid is soybean lecithin; The emulsifier includes 10% polyglyceryl laurate, 15% cocoglycoside, 5% Tween 80; The co-emulsifier is laureth-23; The polyol includes 10% 1,2 pentanediol, 20% glycerol, 10% ethoxydiglycol.

[0072] Comparative example 7: A comparative example of the anti-acne liposome of the present application, the anti-acne liposome of the comparative example differs from example 1 only in that hyssop extract is replaced with the same amount of rosemary extract, and the rest of the components are the same as example 1.

[0073] The preparation method of the anti-acne liposome is the same as example 1.

[0074] Comparative example 8: The present comparative example provides a free composition comprising nicotinamide 8%, Magnolia officinalis bark extract 5%, glycyrrhetinic acid 2%, persicin 2%, Hyssopus officinalis extract 0.1%, dimethyl sulfoxide (DMSO) 8.29%, water 74.61%.

[0075] The preparation method of the free composition comprises the following steps: Mixing Magnolia officinalis bark extract, glycyrrhetinic acid, persicin, nicotinamide, Hyssopus officinalis extract, dimethyl sulfoxide, and water to obtain the free composition.

[0076] Test Example 1: characterization test and stability test Test sample: acne-removing liposomes of Examples 1-4 and Comparative Examples 1-7.

[0077] 1. Use the instrument (particle size analyzer) to detect the particle size and PDI of the test sample.

[0078] The electron microscope observation diagram of the liposomes of Example 1 is shown in Figure 1 The test results show that the average particle size of the acne-removing liposomes of Examples 1-4 and Comparative Examples 1-7 is within 100 nm, and the PDI is 0.05-0.4. Among them, the average particle size of the acne-removing liposomes of Example 1 is 24.68 nm, and the PDI is 0.091; the average particle size of the acne-removing liposomes of Example 2 is 26.87 nm, and the PDI is 0.108; the average particle size of the acne-removing liposomes of Example 3 is 28.36 nm, and the PDI is 0.065; the average particle size of the acne-removing liposomes of Example 4 is 29.21 nm, and the PDI is 0.072; the average particle size of the acne-removing liposomes of Example 5 is 28.16 nm, and the PDI is 0.165; the average particle size of the acne-removing liposomes of Example 6 is 29.52 nm, and the PDI is 0.105.

[0079] The average particle size of the acne-removing liposomes of Comparative Example 1 is 36.18 nm, and the PDI is 0.121; the average particle size of the acne-removing liposomes of Comparative Example 2 is 32.19 nm, and the PDI is 0.216; the average particle size of the acne-removing liposomes of Comparative Example 3 is 30.12 nm, and the PDI is 0.186; the average particle size of the acne-removing liposomes of Comparative Example 4 is 30.31 nm, and the PDI is 0.216; the average particle size of the acne-removing liposomes of Comparative Example 5 is 32.65 nm, and the PDI is 0.106; the average particle size of the acne-removing liposomes of Comparative Example 6 is 31.62 nm, and the PDI is 0.296; the average particle size of the acne-removing liposomes of Comparative Example 7 is 33.82 nm, and the PDI is 0.183.

[0080] 2. The anti-acne liposomes of Examples 1-4 and Comparative Examples 1-7 were placed in airtight containers and stored at -20°C, room temperature, 4°C and 45°C respectively for 3 months, and the stability changes were observed.

[0081] The results showed that the anti-acne liposome samples did not show delamination or separation, and the particle size did not change significantly, indicating that the anti-acne liposomes prepared by the present application had good stability.

[0082] Test Example 2: Evaluation of chicken embryo chorioallantoic membrane irritation The anti-acne liposomes in Examples 1-4 were each diluted 10 times with water, and 200 μL of the diluted anti-acne liposomes were added to the surface of the chicken embryo chorioallantoic membrane. After 300 s, the blood vessel changes were observed, and the initial time of capillary blood vessel congestion, bleeding and coagulation was recorded within 5 min. The irritation score (Irritation score, IS) was calculated according to formula (1): IS = [(301-secH) x 5 + (301-secL) x 7 + (301-secC) x 9] / 300 - Formula (1) In the above formula, secH is the initial time of congestion, s; secL is the initial time of bleeding, s; and secC is the initial time of coagulation, s.

[0083] The mean value of the repeated test results was calculated, and the test substance was classified according to the mean value, wherein 0-0.9, 1.0-4.9, 5.0-8.9 and 9-21.0 were classified as no irritation, mild irritation, moderate irritation and severe irritation, respectively.

[0084] The test results showed that after the anti-acne liposomes diluted 10 times with water were contacted with the chicken embryo chorioallantoic membrane for 300 s, there was no bleeding, no blood vessel fusion, and no coagulation phenomenon. The reaction integral of Examples 1-4 was 0.05, 0.07, 0.06 and 0.07, respectively, indicating that the anti-acne liposomes prepared by the present application had good safety and no irritation.

[0085] Test Example 3: Patch test Ten percent of the anti-acne liposomes described in Examples 1-4 and a blank control were applied to the flexor side of the forearm of 30 test subjects for 24 h. After removing the patch, the skin reaction was observed after 30 min, and the skin reaction was observed again after 24 h and 48 h.

[0086] The results showed that none of the 30 test subjects had symptoms such as faint red spots, red spots, edematous erythema, significant redness, infiltration or papules, and papules or blisters, indicating that the anti-acne liposomes prepared in Examples 1-4 had no irritation to human skin.

[0087] Test Example 4: Measurement of Skin Cumulative Permeation and Skin Storage Franz diffusion cell method was used to carry out the in vitro pig skin permeation experiment. The anti-acne liposomes of Example 1 and the free composition of Comparative Example 8 were diluted to 5% diluent, 0.5 g of each was taken in the supply chamber, PBS (pH 7.4) was used as the receiving liquid, and HPLC analysis was used to calculate the cumulative permeation of the active ingredients (maotai chalcone / nicotinamide) per unit area at different times. After 24 h, the skin homogenate supernatant was taken for HPLC analysis to calculate the skin storage of the active ingredients per unit area. The skin cumulative permeation of the active ingredients at different sampling times was calculated according to formula (2).

[0088] Formula (2) In the above formula, Qn is the cumulative permeation of the drug, 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 amount of each sampling. The cumulative permeation per unit area Q = Qn / S, where S is the area of the diffusion cell 2.27 cm 2 .

[0089] Table 1 The results are shown in Table 1. The 12 h skin cumulative permeation per unit area of maotai chalcone in the free composition and the anti-acne liposomes was 12.48 μg / cm 2 and 28.16 μg / cm 2 , respectively, the 24 h skin cumulative permeation per unit area was 30.47 μg / cm 2 and 69.20 μg / cm 2 , respectively, and the skin storage was 40.39 μg / cm 2 and 98.49 μg / cm 2 , respectively. Compared with free maotai chalcone, the 12 h and 24 h skin cumulative permeation per unit area of maotai chalcone in the anti-acne liposomes increased by 125.64% and 127.11%, respectively, and the skin storage increased by 143.85%.

[0090] The 12 h skin cumulative permeation per unit area of nicotinamide in the free composition and the anti-acne liposomes was 72.12 μg / cm 2 and 92.59 μg / cm 2 , respectively, the 24 h skin cumulative permeation per unit area was 178.18 μg / cm 2 and 316.84 μg / cm 2 , respectively, and the skin storage was 21.41 μg / cm 2 and 86.78 μg / cm 2Compared with free nicotinamide, the cumulative permeation amount of nicotinamide per unit area of skin in the acne-removing liposome increased by 28.38% and 77.86% at 12 h and 24 h, respectively, and the skin storage capacity increased by 305.32%. It is shown that the active ingredient wrapped by the liposome can effectively promote the transdermal absorption and storage of the active ingredient in the skin, and improve the skin bioavailability.

[0091] Test Example 5: Effect of acne-removing liposome on release amount of inflammatory factors Raw 264.7 cells cultured in DMEM medium containing 10% FBS and 1% PS to the exponential growth phase were inoculated in a 24-well plate at 1×10 5 Each sample in the experimental group was added with 0.5 mL of acne-removing liposome prepared by Comparative Examples 1-8 and Examples 1, 5 and 6 (dilution multiples are the same) diluted 2000 times, and Comparative Example 8 was free composition, after 15 h of culture, 4 mg / L of LPS was added to the cells in each group except the blank control group to prepare a cell inflammation model, and the cells were incubated at 37°C for 6 h.

[0092] The upper culture solution was collected, and the expression amounts of IL-1β, IL-6 and IL-8 were detected according to the instructions of the ELISA kit. The results are shown in Table 2.

[0093] Table 2: Test results of release amount of inflammatory factors in each group (n=3) Note: ## indicates p<0.01 compared with the blank control; ** indicates p<0.01 compared with the model; a indicates p<0.01 compared with Comparative Examples 1-5; b indicates p<0.01 compared with Comparative Example 6; c indicates p<0.01 compared with Comparative Example 7; d indicates p<0.01 compared with Comparative Example 8; e indicates p<0.01 compared with Examples 5 and 6.

[0094] The experimental results in Table 2 show that compared with the blank control group, the secretion amounts of IL-1β, IL-6 and IL-8 in the model group significantly increased after the addition of LPS (p<0.01); compared with the model group, the acne-removing liposome / free composition prepared by Example 1, Example 4, Example 5 and Comparative Examples 1-8 can significantly reduce the secretion amounts of IL-1β, IL-6 and IL-8 (p<0.01).

[0095] Example 1 compared with Comparative Example 1-5, the acne-removing liposomes of Example 1 encapsulate five active substances, i.e. nicotinamide, glycyrrhizic acid, persicin, magnolia bark extract and hyssop extract, and the effect of inhibiting Raw 264.7 cells from secreting IL-1β, IL-6 and IL-8 is better than that of the acne-removing liposomes prepared by compounding any four active substances (p<0.01).

[0096] Example 1 compared with Comparative Example 6, the weight ratio of nicotinamide, glycyrrhizic acid, persicin, magnolia bark extract and hyssop extract in Comparative Example 6 is not within the scope of the present application, resulting in a decreased effect of inhibiting Raw 264.7 cells from secreting IL-1β, IL-6 and IL-8, and failing to exert the best effect.

[0097] Example 1 compared with Comparative Example 7, the acne-removing liposomes of Comparative Example 7 replace hyssop extract with rosemary extract, and the effect of inhibiting Raw 264.7 cells from secreting IL-1β, IL-6 and IL-8 is decreased, indicating that the replacement of any component in the acne-removing composition of the present application will affect the anti-inflammatory effect. The reason is that hyssop extract contains monoterpene compounds such as pinocamphone and isopinocamphone, and rosemary acid, and the pinocamphone derivative, when compounded with nicotinamide, glycyrrhizic acid, persicin and magnolia bark extract, can reduce the release of inflammatory factors by directly inhibiting the NF-κB or MAPK signaling pathway, while after being replaced with rosemary extract, the rosemary extract mainly contains carnosic acid, carnosol and rosemary acid, and its anti-inflammatory mechanism relies on the Nrf2 / ARE pathway (antioxidant pathway) and is weak in inhibiting NF-κB and IL-6 and IL-8.

[0098] Example 1 compared with Example 5 and Example 6, the results show that when the mass ratio of glycyrrhizic acid to hyssop extract is (15-20):1, the anti-inflammatory effect is more significant, which is better than that of other mass ratios. When glycyrrhizic acid and hyssop extract are compounded at this specific mass ratio, the glucocorticoid-like effect of glycyrrhizic acid and the direct pathway inhibition of hyssop form a double regulation, covering the upstream and downstream of the inflammatory response (such as glycyrrhizic acid inhibiting transcription factors and hyssop blocking signal transduction), optimizing the bioavailability of the two active ingredients, and avoiding competitive inhibition caused by excessive amount of a certain component (such as high concentration of glycyrrhizic acid may inhibit the effect of certain terpenes in hyssop).

[0099] The acne-removing liposomes prepared in Example 1 compared with the free composition of Comparative Example 8, the effect of Example 1 in inhibiting Raw 264.7 cells from secreting IL-1β, IL-6 and IL-8 is more significant (p<0.01), and the anti-inflammatory effect of the acne-removing composition after being encapsulated is better than that of the free composition at the same dose.

[0100] Test Example 6: Effect of acne-removing liposomes on antibacterial activity A few P. acnes (ATCC 6919) and S. aureus on the surface of the activated culture medium were taken with a swab, added with sterile saline, and blown with a sterile pipette to make the bacteria evenly dispersed in the sterile saline. The concentration of the bacteria was adjusted to be similar to 0.5 McFarland turbidity tube (1.5 x 10 8 After being fixed, a round filter paper (d = 6 mm) was attached to the surface of the culture medium, and 5 μL of the anti-acne liposomes prepared in Comparative Examples 1-8 and Example 1, Example 5, and Example 6 (Comparative Example 8 was a free composition) were added vertically to the filter paper. The plate with the attached drug sensitivity paper was placed in a 37°C incubator, and after overnight culture, the plate was taken out, the diameter of the inhibition zone was measured with a vernier caliper, and the edge of the inhibition zone was recorded as the limit at which no obvious growth of bacteria was observed with the naked eye. The results are shown in Table 3.

[0101] Table 3: Inhibition zone size determined by the paper diffusion method (n = 3) Note: ## indicates p < 0.01 compared with Comparative Examples 1-5; ** indicates p < 0.01 compared with Comparative Example 7; @@ indicates p < 0.01 compared with Comparative Example 8; && indicates p < 0.01 compared with Example 5 and Example 6.

[0102] As can be seen from Table 3, after 5 μL of different test group samples were added to the 6 mm paper, the average diameter of the P. acnes and S. aureus inhibition zone of Example 1 increased more significantly compared with Comparative Examples 1-5, indicating that the liposomes prepared by compounding the five active ingredients of nicotinamide, glycyrrhetinic acid, persicin, Magnolia officinalis bark extract, and Hyptis suaveolens extract have a synergistic effect.

[0103] Example 1 compared with Comparative Example 6, the weight ratio of nicotinamide, glycyrrhetinic acid, persicin, Magnolia officinalis bark extract, and Hyptis suaveolens extract in Comparative Example 6 is not within the scope of the present application, resulting in a decrease in the antibacterial effect and failing to exert the best effect.

[0104] Example 1 compared with Comparative Example 7, the anti-acne liposomes in Comparative Example 7 replace Hyptis suaveolens extract with rosemary extract, resulting in a decrease in the antibacterial effect of P. acnes and S. aureus, indicating that the replacement of any component in the anti-acne composition of the present application will affect the antibacterial efficacy. The reason is that the main active ingredients of rosemary extract include salvia acid and salvia phenol, the main active ingredients of Hyptis suaveolens extract include pinocamphone and isopinocamphone, Hyptis suaveolens extract contains a unique and efficient membrane-destroying component (such as pinocamphone), and has significant anti-inflammatory, antioxidant, antibacterial, and skin barrier repair effects. Although rosemary extract has certain anti-inflammatory efficacy, it is weak in regulating sebum secretion, inhibiting P. acnes, or promoting keratin metabolism, resulting in a failure to exert better antibacterial efficacy when compounded with other components.

[0105] The results of Example 1 compared with Example 5, Example 6 show that when the mass ratio of glycyrrhetinic acid:Hyssopus extract is (15-20):1, the inhibitory effect on P. acnes and S. aureus is better than other mass ratios. When glycyrrhetinic acid and Hyssopus extract are compounded at this specific mass ratio, glycyrrhetinic acid can inhibit the NF-κB pathway, reduce neutrophil infiltration, and indirectly reduce the survival environment of bacteria (changes in pH and nutrient supply at the inflammation site). Hyssopus extract can scavenge ROS and prevent bacteria from activating virulence genes (such as the agr quorum sensing system of S. aureus) using oxidative stress, and glycyrrhetinic acid can preferentially control inflammation, while Hyssopus extract can assist in direct sterilization, avoiding the development of antibiotic resistance (such as the tolerance phenotype of S. aureus) caused by excessive inflammation, thereby significantly improving the bacteriostatic effect.

[0106] The acne-removing liposomes prepared in Example 1 have a better inhibitory effect on P. acnes and S. aureus than the free composition of Comparative Example 8 at the same dose.

[0107] Finally, it should be noted that the above examples are only used to illustrate the technical solutions of the present application and do not limit the scope of protection of the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present application.

Claims

1. An acne treatment composition characterized in that, The components include the following weight parts: nicotinamide 2-8 parts, magnolia bark extract 1-5 parts, glycyrrhizinic acid 0.15-2.01 parts, paeonol 0.1-2 parts, and hyssop extract 0.01-0.15 parts.

2. The acne treatment composition of claim 1, wherein The mass ratio of the glycyrrhizinic acid and the hyssop extract is glycyrrhizinic acid:hyssop extract= (15-20):

1.

3. An anti-acne liposome, characterized by, The acne-removing liposome comprises the acne-removing composition and a liposome carrier auxiliary material; the liposome carrier auxiliary material comprises phospholipid, emulsifier, co-emulsifier, polyol, and water.

4. The acne-removing liposome as described in claim 3, characterized in that, The acne-removing liposome comprises the following components in the following mass percentages: acne-removing composition 3.26-17.1%, phospholipid 0.1-5%, emulsifier 10-30%, co-emulsifier 1-5%, polyol 10-40%, and the balance of water.

5. The acne-removing liposome as described in claim 3, characterized in that, The phospholipid comprises at least one of soybean lecithin, hydrogenated lecithin, egg yolk lecithin, hydrogenated soybean lecithin, and hydrogenated egg yolk lecithin; And / or, the emulsifier comprises at least one of polyoxyethylene castor oil emulsifier, polyoxyethylene hydrogenated castor oil emulsifier, polyglycerin emulsifier, poloxamer, coco-glucoside, triglyceride, pyrrolidone, polyglyceryl acid ester, polyglyceryl lactic acid ester, polyglyceryl stearic acid ester, polyglyceryl capryl / capric acid ester, polyglyceryl lauric acid ester, Tween 80, Tween 20, Tween 60, PEG-20 hydrogenated castor oil, PEG-40 hydrogenated castor oil, and PEG-60 hydrogenated castor oil; And / or, the co-emulsifier comprises at least one of lauryl polyoxyl-23, diethylene glycol monoethyl ether, PPG-26-butanol polyoxyl-26, tridecyl alcohol polyoxyl-12; And / or, the polyol comprises at least one of glycerol, propylene glycol, 1,3-butanediol, 2,3-butanediol, 1,3-propanediol, 1,2-pentanediol, ethoxydiglycol, 1,2-hexanediol, dipropylene glycol, isopropyl alcohol, polyethylene glycol-200, PPG-10 sorbitol, octyldodecanol, and butylene glycol.

6. The method of claim 3-5, wherein the liposomes are prepared by the following steps: 1) dissolving the liposome components in a suitable solvent, 2) removing the solvent, 3) adding the active ingredient, and 4) adding the stabilizing agent. The method comprises the following steps: (1) mixing the magnolia bark extract, glycyrrhizinic acid, paeonol, emulsifier, co-emulsifier, polyol, and phospholipid to obtain a mixed solution A; (2) mixing the nicotinamide, hyssop 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.

7. The production method according to claim 6, wherein The nanofication treatment comprises extrusion, ultrasonic, or homogenization.

8. The production method according to claim 7, wherein The homogenization is performed at 500-1000 bar.

9. Use of the acne-removing composition of claim 1 or 2, or the acne-removing liposome of any one of claims 3-5 in an acne-removing product.

10. An anti-acne product, characterized in that, The acne-removing composition of claim 1 or 2, or the acne-removing liposome of any one of claims 3-5.

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