Tranexamic acid liposomes, their preparation method and applications

Abstract

This invention provides tranexamic acid liposomes, their preparation method, and applications, relating to the field of nanoliposome technology. This invention utilizes a simple process to prepare tranexamic acid liposomes by rationally combining the ratios of tranexamic acid, phospholipids, and cholesterol. This invention achieves high loading capacity and high loading rate for the active ingredient tranexamic acid, maintaining its stability for a long time under various temperature conditions. The tranexamic acid liposomes prepared by this invention have a particle size between 10-50 nm, enabling better penetration into the stratum corneum and targeting the basal layer of the skin, providing a long-lasting and stable effect. Compared to liposomes prepared by other processes, they exhibit excellent transdermal permeability and skin retention, which is more conducive to the efficacy of the active ingredient, significantly improving its bioavailability and resulting in a greater skin-lightening effect.

Description

Technical Field

[0001] This invention relates to the field of nanoliposome technology, specifically to a tranexamic acid liposome, its preparation method, and its application. Background Technology

[0002] Skin whitening is a long-standing skincare benefit favored by many Chinese consumers and a key area of ​​research and development for major skincare products. Chinese skin is prone to blemishes such as freckles and melasma, and consumers hope to use whitening skincare products to lighten these spots and improve uneven skin tone on the face and other parts of the body, resulting in brighter, more natural-looking skin. However, consumers also expect whitening products to be safe and non-irritating, making them more suitable for the skin characteristics of Chinese people and aligning with environmental concerns.

[0003] Tranexamic acid, meaning "transmitting brightness," is listed as tranexamic acid in the Chinese cosmetics catalog under the INCI name tranexamic acid, while its standard name as a prescription drug is tranexamic acid. In 1950, Japanese pharmacologists discovered that tranexamic acid had good hemostatic properties, hence the name tranexamic acid. In 1970, a Japanese doctor accidentally discovered that tranexamic acid could fade melasma, a discovery that attracted significant attention from both the medical and cosmetic raw material industries. In 1979, Japanese doctor Nijo formally reported the effects of tranexamic acid on melasma, and tranexamic acid gradually became used to prevent and treat pigmentation and blemishes. Tranexamic acid inhibits the catalytic action of proteases on peptide bond hydrolysis, thereby preventing the activity of enzymes such as proteases, thus inhibiting the disordered function of epidermal cells in the dark spots, suppressing melanin-enhancing factors, and completely cutting off the pathway of melanin formation caused by ultraviolet radiation. Therefore, in recent years, its application in whitening creams and lotions, as well as in high-tech whitening microneedling, has become increasingly common.

[0004] Currently, most technologies prepare tranexamic acid into topical creams. However, these creams suffer from low levels of active ingredients and large molecular sizes, making it difficult for them to penetrate the stratum corneum and reach deeper layers of the skin. This significantly limits the bioavailability of tranexamic acid and its application. Publications CN 113679631 A and CN 109481321 A disclose methods for preparing tranexamic acid into liposomes for use in cosmetics. However, the methods provided by these publications can only achieve a maximum loading of 6% of the effective amount of tranexamic acid, with a loading rate below 95% and a product particle size exceeding 100 nm. Therefore, there is an urgent need for a long-term stable and continuously effective tranexamic acid liposome that can target the deep layers of the skin to achieve whitening effects, possessing high loading capacity and high loading rate. Summary of the Invention

[0005] (a) Technical problems to be solved

[0006] To address the shortcomings of existing technologies, this invention provides a tranexamic acid liposome, its preparation method, and its application.

[0007] (II) Technical Solution

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] First, the present invention provides a tranexamic acid liposome, which is composed of the following raw materials in parts by weight: 1-20 parts of polyol; 6-12 parts of tranexamic acid; 1-5 parts of phospholipid; 1-5 parts of cholesterol; 0.1-5 parts of emollient; 0.1-2 parts of antioxidant; and 70-90 parts of water.

[0010] Furthermore, the tranexamic acid liposome is composed of the following raw materials in parts by weight: 5-15 parts polyol; 8-10 parts tranexamic acid; 1-3 parts phospholipid; 1-2 parts cholesterol; 0.5-2 parts emollient; 0.5-1 part antioxidant; and 75-85 parts water.

[0011] Specifically, the polyol is one or more of glycerol, butanediol, 1,2-hexanediol, 1,3-propanediol, polyethylene glycol, and PPG sorbitol.

[0012] Specifically, the phospholipid is one or more of the following: lecithin, hydrogenated lecithin, soybean lecithin, egg yolk lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine.

[0013] Specifically, the emollient is one or more of the following: jojoba seed oil, hydrogenated palm kernel oil, isosorbide dimethyl ether, glyceryl stearate, and caprylic / capric triglyceride.

[0014] Specifically, the antioxidant is one or more of carnosine, palmitoyl pentapeptide-4, p-hydroxyacetophenone, and tocopherol (vitamin E).

[0015] Preferably, the mass ratio of tranexamic acid, phospholipids, and cholesterol is (8-10):(1-3):(1-2).

[0016] Preferably, the mass ratio of tranexamic acid, phospholipids, and cholesterol is 10:2:1.

[0017] The present invention also provides a method for preparing tranexamic acid liposomes, wherein the tranexamic acid liposomes are prepared according to the following steps:

[0018] S1: Weigh each raw material according to the above weight proportions, and add phospholipids, cholesterol, emollients and / or fat-soluble antioxidants into a dry single-necked round flask in sequence. Dissolve them in anhydrous ethanol to obtain a lipid mixture.

[0019] S2: Perform rotary evaporation on the mixed solution in step 1. After the solvent is removed, a lipid film will form on the inner wall of the flask. Add organic solvent again and rotary evaporate. Repeat this step 1-3 times until a uniform lipid film forms on the inner wall of the flask.

[0020] S3: Tranexamic acid, polyol and / or water-soluble antioxidant and water are magnetically stirred until completely dissolved to obtain an active ingredient solution;

[0021] S4: Add the active ingredient solution of S3 to the flask in S2, and obtain the crude liposome solution by ultrasonic treatment in a constant temperature water bath.

[0022] S5: The crude suspension of S4 was homogenized using a high-pressure homogenizer to obtain tranexamic acid nanoliposomes.

[0023] Specifically, in step S2, the rotary evaporation conditions are reduced pressure rotary evaporation at 40-60℃.

[0024] Specifically, the magnetic stirring conditions in step S3 are 100-300 rpm for 20-40 minutes.

[0025] Specifically, the ultrasonic treatment conditions in step S4 are 30-50℃ for 30-60 minutes.

[0026] Specifically, in step S5, the high-pressure homogenization is performed 1-5 times at 100-800 bar.

[0027] (III) Beneficial Effects

[0028] This invention utilizes a simple process to prepare tranexamic acid liposomes by rationally combining the ratios of tranexamic acid, phospholipids, and cholesterol. The liposomes prepared using the process and ingredient ratios provided by this invention achieve high loading capacity and high loading rate of the active ingredient tranexamic acid, maintaining its stability over a long period under various temperature conditions. The tranexamic acid liposomes prepared by this invention have a particle size between 10-50 nm, enabling better penetration into the stratum corneum and targeting of the basal layer of the skin, providing a long-lasting and stable effect. Compared to liposomes prepared by other processes, they exhibit excellent transdermal permeability and skin retention, which is more conducive to the efficacy of the active ingredient and significantly improves its bioavailability, resulting in a greater spot-removing effect. Attached Figure Description

[0029] Figure 1 The particle size distributions are for the tranexamic acid liposome samples prepared in Examples 1-9 and Comparative Examples 1-6.

[0030] Figure 2The cumulative permeation (A) and retention (B) results of the tranexamic acid liposome samples prepared in Example 1 and Comparative Examples 1-6 are shown; * indicates p<0.05; ** indicates p<0.01.

[0031] Figure 3 The skin gloss was measured 28 days after using the tranexamic acid liposome sample prepared in Example 1, where ΔGloss(A) and ΔDSC(B) are used; ** indicates p<0.01. Detailed Implementation

[0032] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] Example 1

[0034] A tranexamic acid liposome is prepared according to the following steps:

[0035] S1: Add 2 parts hydrogenated lecithin, 1 part cholesterol, 0.5 parts jojoba seed oil and 0.5 parts palmitoyl pentapeptide-4 to a dry single-necked round flask in sequence, and dissolve in anhydrous ethanol to obtain a lipid mixture.

[0036] S2: The lipid mixture in S1 is subjected to rotary evaporation under reduced pressure at 40-60℃. After the solvent is removed, a lipid film will form on the inner wall of the flask. Organic solvent is added again and rotary evaporation is performed. This step is repeated twice until a uniform lipid film is formed on the inner wall of the flask.

[0037] S3: Dissolve 10 parts tranexamic acid, 10 parts butanediol, and the remainder pure water by magnetic stirring at 300 rpm for 20 min to obtain an active ingredient solution.

[0038] S4: Add the active ingredient solution of S3 to the flask in S2, and sonicate it in a 30℃ constant temperature water bath for 50 min to obtain a crude liposome solution.

[0039] S5: The crude liposome solution of S4 was homogenized using a high-pressure homogenizer at a pressure of 600 bar for 3 cycles to obtain tranexamic acid nanoliposomes.

[0040] Example 2

[0041] A tranexamic acid liposome, wherein 100 parts of tranexamic acid liposome are prepared according to the following steps:

[0042] S1: Add 2 parts soybean lecithin, 2 parts cholesterol, 2 parts hydrogenated palm kernel oil and 1 part vitamin E to a dry single-necked round flask in sequence, add anhydrous ethanol as an organic solvent to dissolve, and obtain a lipid mixture.

[0043] S2: The lipid mixture in S1 is subjected to rotary evaporation under reduced pressure at 40-60℃. After the solvent is removed, a lipid film will form on the inner wall of the flask. Organic solvent is added again and rotary evaporation is performed. This step is repeated once until a uniform lipid film is formed on the inner wall of the flask.

[0044] S3: Dissolve 10 parts tranexamic acid, 8 parts 1,3-propanediol, and the remainder pure water by magnetic stirring at 100 rpm for 40 min to obtain an active ingredient solution.

[0045] S4: Add the active ingredient solution of S3 to the flask in S2, and sonicate it in a constant temperature water bath at 40℃ for 50 min to obtain a crude liposome solution.

[0046] S5: The crude liposome solution of S4 was homogenized using a high-pressure homogenizer at a pressure of 500 bar for 4 cycles to obtain tranexamic acid nanoliposomes.

[0047] Example 3

[0048] A tranexamic acid liposome, wherein 100 parts of tranexamic acid liposome are prepared according to the following steps:

[0049] S1: Add 2 parts lecithin, 1 part egg yolk lecithin, 2 parts cholesterol, and 1 part jojoba seed oil to a dry single-necked round flask in sequence, and dissolve them in anhydrous ethanol to obtain a lipid mixture.

[0050] S2: The lipid mixture in S1 is subjected to rotary evaporation under reduced pressure at 40-60℃. After the solvent is removed, a lipid film will form on the inner wall of the flask. Organic solvent is added again and rotary evaporation is performed. This step is repeated 3 times until a uniform lipid film is formed on the inner wall of the flask.

[0051] S3: Dissolve 8 parts tranexamic acid, 10 parts glycerol, 1 part carnosine, and the remainder in pure water by magnetic stirring at 200 rpm for 30 min to obtain an active ingredient solution.

[0052] S4: Add the active ingredient solution of S3 to the flask in S2, and sonicate it in a constant temperature water bath at 40℃ for 50 min to obtain a crude liposome solution.

[0053] S5: The crude liposome solution of S4 was homogenized using a high-pressure homogenizer at a pressure of 300 bar for 5 cycles to obtain tranexamic acid nanoliposomes.

[0054] Example 4

[0055] A tranexamic acid liposome, wherein 100 parts of tranexamic acid liposome are prepared according to the following steps:

[0056] S1: Add 1 part soybean lecithin, 1 part cholesterol, and 0.5 parts caprylic / capric triglyceride to a dry single-necked round flask in sequence, and dissolve them in anhydrous ethanol to obtain a lipid mixture.

[0057] S2: The lipid mixture in S1 is subjected to rotary evaporation under reduced pressure at 40-60℃. After the solvent is removed, a lipid film will form on the inner wall of the flask. Organic solvent is added again and rotary evaporation is performed. This step is repeated twice until a uniform lipid film is formed on the inner wall of the flask.

[0058] S3: Dissolve 8 parts tranexamic acid, 5 parts polyethylene glycol, 0.5 parts p-hydroxyacetophenone, and the remainder is pure water in a magnetically stirred solution at 300 rpm for 20 min to obtain an active ingredient solution.

[0059] S4: Add the active ingredient solution of S3 to the flask in S2, and sonicate it in a 30℃ constant temperature water bath for 50 min to obtain a crude liposome solution.

[0060] S5: The crude liposome solution of S4 was homogenized using a high-pressure homogenizer at a pressure of 600 bar for 3 times to obtain tranexamic acid nanoliposomes.

[0061] Example 5

[0062] A tranexamic acid liposome, wherein 100 parts of tranexamic acid liposome are prepared according to the following steps:

[0063] S1: Add 2 parts hydrogenated lecithin, 2 parts phosphatidylcholine, 3 parts cholesterol, 5 parts isosorbide dimethyl ether and 1 part vitamin E to a dry single-necked round flask in sequence, and dissolve in anhydrous ethanol to obtain a lipid mixture.

[0064] S2: The lipid mixture in S1 is subjected to rotary evaporation under reduced pressure at 40-60℃. After the solvent is removed, a lipid film will form on the inner wall of the flask. Organic solvent is added again and rotary evaporation is performed. This step is repeated once until a uniform lipid film is formed on the inner wall of the flask.

[0065] S3: Dissolve 12 parts tranexamic acid, 4 parts butanediol, 4 parts PPG sorbitol, and the remainder pure water in a magnetically stirred solution at 100 rpm for 40 min to obtain an active ingredient solution.

[0066] S4: Add the active ingredient solution of S3 to the flask in S2, and sonicate it in a constant temperature water bath at 40℃ for 50 min to obtain a crude liposome solution.

[0067] S5: The crude liposome solution of S4 was homogenized using a high-pressure homogenizer at a pressure of 500 bar for 4 cycles to obtain tranexamic acid nanoliposomes.

[0068] Example 6

[0069] A tranexamic acid liposome, wherein 100 parts of tranexamic acid liposome are prepared according to the following steps:

[0070] S1: Add 3 parts hydrogenated lecithin, 2 parts phosphatidylinositol, 4 parts cholesterol, and 1 part jojoba seed oil to a dry single-necked round flask in sequence, and dissolve them in anhydrous ethanol to obtain a lipid mixture.

[0071] S2: The lipid mixture in S1 is subjected to rotary evaporation under reduced pressure at 40-60℃. After the solvent is removed, a lipid film will form on the inner wall of the flask. Organic solvent is added again and rotary evaporation is performed. This step is repeated 3 times until a uniform lipid film is formed on the inner wall of the flask.

[0072] S3: Dissolve 12 parts tranexamic acid, 8 parts 1,2-hexanediol, 1 part carnosine, and the remainder pure water in a magnetically stirred solution at 200 rpm for 30 min to obtain an active ingredient solution.

[0073] S4: Add the active ingredient solution of S3 to the flask in S2, and sonicate it in a constant temperature water bath at 40℃ for 50 min to obtain a crude liposome solution.

[0074] S5: The crude liposome solution of S4 was homogenized using a high-pressure homogenizer at a pressure of 300 bar for 5 cycles to obtain tranexamic acid nanoliposomes.

[0075] Example 7

[0076] The difference between this embodiment and Example 1 is that each 100 parts of tranexamic acid liposomes consists of the following parts by weight of raw materials: 10 parts of tranexamic acid, 1 part of lecithin, 1 part of egg yolk lecithin, 1 part of cholesterol, 0.5 parts of jojoba seed oil, 0.5 parts of palmitoyl pentapeptide-4, 10 parts of butylene glycol, and the remainder is purified water.

[0077] Example 8

[0078] The difference between this embodiment and Example 1 is that each 100 parts of tranexamic acid liposomes consists of the following parts by weight of raw materials: 10 parts tranexamic acid, 1.5 parts hydrogenated lecithin, 0.5 parts phosphatidylethanolamine, 1 part cholesterol, 0.5 parts jojoba seed oil, 0.5 parts palmitoyl pentapeptide-4, 10 parts butylene glycol, and the remainder is purified water.

[0079] Example 9

[0080] The difference between this embodiment and Example 1 is that each 100 parts of tranexamic acid liposomes consists of the following parts by weight of raw materials: 10 parts tranexamic acid, 2 parts soybean lecithin, 1 part cholesterol, 0.5 parts jojoba seed oil, 0.5 parts palmitoyl pentapeptide-4, 10 parts butylene glycol, and the remainder being purified water.

[0081] Comparative Example 1

[0082] The difference between this embodiment and Embodiment 1 is that each 100 parts of tranexamic acid liposomes consists of the following parts by weight of raw materials: 10 parts tranexamic acid, 0.5 parts hydrogenated lecithin, 0.5 parts cholesterol, 0.5 parts jojoba seed oil, 0.5 parts palmitoyl pentapeptide-4, 10 parts butylene glycol, and 78 parts water.

[0083] Comparative Example 2

[0084] The difference between this embodiment and Embodiment 1 is that each 100 parts of tranexamic acid liposomes is composed of the following parts by weight of raw materials: 10 parts tranexamic acid, 6 parts hydrogenated lecithin, 6 parts cholesterol, 0.5 parts jojoba seed oil, 0.5 parts palmitoyl pentapeptide-4, 10 parts butylene glycol, and 67 parts water.

[0085] Comparative Example 3

[0086] The difference between this embodiment and Embodiment 1 is that each 100 parts of tranexamic acid liposomes consists of the following parts by weight of raw materials: 10 parts tranexamic acid, 5.5 parts hydrogenated lecithin, 0.5 parts cholesterol, 0.5 parts jojoba seed oil, 0.5 parts palmitoyl pentapeptide-4, 10 parts butylene glycol, and 67 parts water.

[0087] Comparative Example 4

[0088] The difference between this embodiment and Embodiment 1 is that each 100 parts of tranexamic acid liposomes consists of the following parts by weight of raw materials: 10 parts tranexamic acid, 0.5 parts hydrogenated lecithin, 5.5 parts cholesterol, 0.5 parts jojoba seed oil, 0.5 parts palmitoyl pentapeptide-4, 10 parts butylene glycol, and 67 parts water.

[0089] Comparative Example 5

[0090] A tranexamic acid liposome is prepared according to the following steps:

[0091] S1: 2 parts hydrogenated lecithin, 1 part cholesterol, 0.5 parts jojoba seed oil and 0.5 parts palmitoyl pentapeptide-4 are added sequentially to the oil phase premix system and stirred until homogeneous to obtain an oil phase mixture.

[0092] S2: Dissolve 10 parts tranexamic acid, 10 parts butanediol, and the remainder pure water by magnetic stirring at 300 rpm for 20 min to obtain an aqueous mixture.

[0093] S3: Add the oil phase mixture of S1 to the aqueous phase mixture in S2, and then sonicate in a 30℃ constant temperature water bath for 50 min to obtain a crude liposome solution.

[0094] S4: The crude liposome solution of S3 was homogenized using a high-pressure homogenizer at a pressure of 600 bar for 3 times to obtain tranexamic acid nanoliposomes.

[0095] Comparative Example 6

[0096] A tranexamic acid liposome is prepared according to the following steps:

[0097] S1: 2 parts hydrogenated lecithin, 1 part cholesterol, 0.5 parts jojoba seed oil and 0.5 parts palmitoyl pentapeptide-4 are added sequentially to the oil phase premix system and stirred until homogeneous to obtain an oil phase mixture.

[0098] S2: Dissolve 10 parts tranexamic acid, 10 parts butanediol, and the remainder is pure water by stirring at a temperature above 50°C to obtain an aqueous mixture.

[0099] S3: Add the oil phase mixture of S1 to the aqueous phase mixture in S2, stir for more than 60 minutes to obtain a mixed phase solution;

[0100] S4: The mixed phase solution of S3 was homogenized using a high-pressure homogenizer at a pressure of 600 bar for 3 cycles to obtain tranexamic acid nanoliposomes.

[0101] Comparative Example 7

[0102] A certain commercially available brand of moisturizing lotion contains approximately 5% tranexamic acid.

[0103] Comparative Example 8

[0104] The basic skincare gel formula consists of: 10% glycerin, 1%-2% carboxymethyl cellulose (aqueous gel matrix), 2%-5% olive oil, 1%-2% sucrose stearate, 1%-2% benzyl alcohol (preservative), 0.5%-1% vitamin E, 0.1%-0.5% pentapeptide, and the remainder being purified water.

[0105] Preparation method: Place glycerin, aqueous gel matrix, oily components, and emulsifier into a container and stir until a gel is formed; add preservatives, fragrances, antioxidants, and peptide components, and continue stirring until homogeneous.

[0106] Experimental Example 1

[0107] Stability test

[0108] The samples prepared in Examples 1-9 and Comparative Examples 1-6 of this invention were placed in sealed containers and stored at -18°C, 4°C, room temperature, and 45°C for 90 days. The properties of the samples were checked at room temperature after the initial state and after 90 days to see if any precipitation or stratification occurred. After being stored at -18°C, 4°C, room temperature, and 45°C for 90 days, no aggregation or stratification occurred, and no active ingredient leakage was observed.

[0109] The retention rate of active substances in the samples was tested by HPLC. After basic calibration, standard solutions were injected sequentially into the HPLC instrument, and peak areas were recorded to establish a standard curve with concentration. The sample solutions to be tested were then injected into the HPLC instrument, and peak areas were recorded. The content of the active substance was calculated based on the standard curve.

[0110] Active ingredient loading rate (%) = (tested active ingredient content ÷ active ingredient feed amount) × 100%.

[0111] As shown in Table 1, compared with the comparative samples 1-6, the samples prepared in Examples 1-9 of this invention all exhibited better stability, and the active ingredient loading rate could be maintained above 96% for a relatively long time under various temperature conditions. The liposome solution provided by this invention has good stability and can be stably compounded in finished product formulations.

[0112] Table 1. Stability test results of samples from Examples 1-9 and Comparative Examples 1-6

[0113]

[0114]

[0115]

[0116] Experimental Example 2

[0117] Product particle size testing

[0118] The liposome samples of Examples 1-9 and Comparative Examples 1-6 were analyzed using a particle size analyzer (model: Zetasizer Pro). First, the samples needed to be diluted appropriately within the range of 10-1000 times. Examples 1-6 were diluted 10-fold before testing. The tests were conducted according to the preset parameters and procedures, and the results are as follows: Figure 1 As shown, the liposome samples prepared in Examples 1-9 have a particle size range of 10-50 nm (PDI < 0.1), while the particle sizes of Comparative Examples 1-6 are all above 90 nm. This result indicates that the liposomes prepared according to the method provided by this invention have smaller particle sizes. Smaller particle sizes are more conducive to the penetration of active substances through the skin barrier, thus improving the transdermal performance of the active substances.

[0119] Experimental Example 3

[0120] Product transdermal test

[0121] The in vitro release behavior of the liposomes prepared in this invention was studied using a vertical Franz diffusion cell method. Piglet skin was used as a carrier and fixed between the supply and receiving chambers of a Franz diffusion cell. The diffusion cell was fixed in a transdermal absorption diffusion apparatus. With the magnetic stir bar and constant temperature water bath activated, the test group consisted of tranexamic acid liposomes prepared in Example 1 (diluted to an active ingredient content of 3%) added to the skin surface in the chamber. A control group was also set up, with samples from Comparative Examples 1-6 diluted to maintain the same active ingredient content as the test sample in Example 1. Transdermal experiments were then conducted on each control group. The cumulative permeation and retention rates were calculated after 24 hours. The results were then analyzed after the in vitro transdermal experiments. The results are as follows: Figure 2 As shown.

[0122] The results showed that after 24 hours, the cumulative skin penetration and retention of the tranexamic acid liposomes prepared in Example 1 were significantly higher than those in Comparative Examples 1-6 (P<0.05). This indicates that the tranexamic acid liposomes prepared according to the method provided in this invention have good transdermal permeability and skin retention capacity, which is more conducive to the efficacy of the active ingredients.

[0123] Test Example 4

[0124] Product safety testing

[0125] Test samples: The samples prepared in Examples 1-9 were diluted with water to a content of 1% of active ingredient.

[0126] Test Method: Fifty healthy rabbits, weighing (2.0±0.2) kg, were randomly divided into 10 groups of 5 rabbits each. 24 hours before the experiment, the hair on both sides of the rabbits' backs was removed, and the skin was checked for injuries before the experiment; injured skin could not be used for skin irritation testing. The hair removal area was approximately 3cm × 3cm on each side. The active ingredient concentration of Examples 1-9 was diluted with water to 1% and applied to the hair-removed area on the left side of the rabbit's back as the test group. A blank aqueous sample was used as the control and applied to the hair-removed area on the right side of the rabbit's back. 1 ml was applied to the test area three times a day for seven consecutive days. The results were observed and are shown in Table 2. No congestion or redness was observed after applying the diluted solutions of Examples 1-9 to the rabbit skin. This indicates that the liposomes prepared in this invention can be safely used in skincare products.

[0127] Table 2. Results of observation on skin irritation of rabbits by samples prepared in Examples 1-9.

[0128]

[0129] Note: "+" indicates congestion and swelling of the rabbit's skin; "++" indicates that the congestion and swelling are still present but are increasing; "-" indicates no congestion or swelling.

[0130] Experimental Example 5

[0131] Product testing for treating melasma.

[0132] Test subjects: 30 qualified volunteers with obvious melasma on their faces and no history of skin allergies were selected. Half-face control was used in the double-blind test.

[0133] Experimental group: 5% of the total amount of Example 1 was added to the blank gel prepared in Comparative Example 8 once a week for 12 consecutive weeks. Volunteers were required to perform daily moisturizing and sun protection.

[0134] Control group 1: The blank gel prepared in Comparative Example 8 served as control group 2. Volunteers were required to perform daily moisturizing and sun protection once a week for 12 consecutive weeks.

[0135] Control group 2: The ordinary tranexamic acid emulsion used in control group 7 was used as control group 1. It was applied once a week for 12 consecutive weeks. Volunteers were required to perform daily moisturizing and sun protection.

[0136] Testing method: The MASI score was used to assess the melasma on the volunteers' faces before and after treatment. The scores were based on three indicators: pigmentation depth, uniformity, and area. The higher the score, the more severe the melasma symptoms.

[0137] Test Results: As shown in Table 3, before treatment, there was no statistically significant difference in MASI scores between the experimental group and control group 2 compared to control group 1 (P > 0.05). After treatment, there was no statistically significant difference in MASI scores between control group 2 and control group 1 (P > 0.05), but a statistically significant difference in MASI scores was observed in the experimental group (P < 0.05). There was no statistically significant difference in MASI scores between control group 1 and control group 2 before and after treatment (P > 0.05). The MASI score of the experimental group after treatment was significantly lower than that before treatment (P < 0.05).

[0138] The above results indicate that the gel containing tranexamic acid liposomes prepared in this invention has a significant therapeutic effect on melasma. The tranexamic acid liposomes of this invention can significantly improve the bioavailability of the active ingredients, thereby enabling them to exert a greater effect in removing melasma.

[0139] Table 3 Comparison of MASI scores before and after treatment in the two groups

[0140]

[0141]

[0142] Note: *Compared with control group 1, *P<0.05; # Compared with before treatment, # P < 0.05.

[0143] Experimental Example 6

[0144] Test subjects: 30 participants (aged 30-50), including 23 women and 7 men. The test was a double-blind test with half-face control.

[0145] Test sample: A tranexamic acid emulsion containing 5% of the one prepared in Example 1 was used as the test sample, with the base emulsion as the control. The dosage was 2 mg / cm³. 2 The basic emulsion formula is as follows: 60 parts purified water; 20 parts glycerin; 10 parts cetearyl alcohol; 5 parts palmitic acid; 5 parts stearic acid.

[0146] Evaluation period: Skin condition was tested on the 14th and 28th days of use.

[0147] Assessment dimension: Test the skin's radiance.

[0148] Assessment method: The skin glossiness was tested using a Glossymeter GL200. The higher the ΔDSC and ΔGloss values, the better the skin glossiness.

[0149] Evaluation Results: After 28 consecutive days of use, the skin radiance in the test group was significantly improved compared to the control group (**, indicating p<0.01, highly significant difference). Results are as follows... Figure 3 As shown.

[0150] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A riboflavin liposome, characterized by, The tartrazine liposome is composed of 10 parts of butanediol, 10 parts of tartrazine, 2 parts of hydrogenated lecithin, 1 part of cholesterol, 0.5 part of emollient, 0.5 part of fat-soluble antioxidant, and 76 parts of water per 100 parts by weight; The tartrazine liposome is prepared according to the following steps: S1: The raw materials are weighed according to the above weight fractions, and the hydrogenated lecithin, cholesterol, emollient and fat-soluble antioxidant are sequentially added to a dry single-neck round flask, dissolved in anhydrous ethanol to obtain a lipid mixture; S2: The lipid mixture in step S1 is subjected to rotary evaporation treatment, and after the solvent is removed, a lipid film will form on the inner wall of the flask. Anhydrous ethanol is added again, and rotary evaporation is performed. This step is repeated 1-3 times until a uniform lipid film forms on the inner wall of the flask; S3: The tartrazine, butanediol and water are magnetically stirred until completely dissolved to obtain an active substance solution; S4: The active substance solution of S3 is added to the flask in S2, and a crude liposome solution is obtained by ultrasonic treatment in a constant temperature water bath; S5: The crude suspension of S4 is subjected to homogenization treatment using a high-pressure homogenizer to obtain tartrazine nanoliposomes. The particle size of the tartrazine liposome is 10-50 nm, and the PDI is <0.

1.

2. The emicizumab liposome according to claim 1, wherein The emollient is one or more of Simmondsia chinensis seed oil, hydrogenated palm kernel oil, isosorbide dimethyl ether, glycerol stearate, and caprylic / capric triglyceride.

3. The emicizumab liposome according to claim 1, wherein The fat-soluble antioxidant is one or more of palmitoyl pentapeptide-4 and vitamin E.

4. Use of the tartrazine liposome of claim 1 in the preparation of a cosmetic product having a spot-removing and whitening effect.

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