Tranexamic acid nano liquid and preparation method thereof

Abstract

The invention provides tranexamic acid nano liquid and a preparation method thereof. The tranexamic acid nano liquid is prepared from the following components in percentage by mass: 10 to 30 percent of tranexamic acid, 5 to 15 percent of lecithin, 5 to 20 percent of capric triglyceride, 9 to 30 percent of water, 0.1 to 0.5 percent of antioxidant and the balance of glycerol. The tranexamic acid nano liquid prepared by the invention can effectively promote tranexamic acid to penetrate through the skin cuticle, not only improves the drug loading capacity, but also effectively improves the cumulative penetration amount and retention amount of tranexamic acid cream, has better stability performance under long-term storage, and improves the whitening and freckle-removing effects of tranexamic acid.

Description

Technical Field

[0001] The invention belongs to the technical field of whitening and freckle-removing cosmetics, and particularly relates to a tranexamic acid nanofluid and a preparation method thereof. Background Art

[0002] Tranexamic acid is a synthetic amino acid that inhibits the catalytic effect of proteases on peptide bond hydrolysis, thereby blocking the activity of enzymes such as inflammatory proteases. This in turn suppresses the dysfunction of epidermal cells in the area of ​​dark spots and inhibits the melanin-enhancing factor complex, completely shutting down the melanin production pathway caused by UV exposure. Its mechanism of action encompasses multiple steps in the melanin synthesis pathway and, compared to traditional whitening ingredients like hydroquinone, offers greater safety and lower irritation. Therefore, it is recognized as a leading new-generation whitening active ingredient.

[0003] In practical applications for whitening and freckle removal, tranexamic acid must be absorbed transdermally to reach its target melanocytes in the basal layer of the epidermis and dermis to exert its efficacy. Currently available products often utilize a water-soluble matrix to directly incorporate tranexamic acid. While this ensures ingredient stability, the transdermal absorption rate and skin retention of tranexamic acid in these formulations are low, making them ineffective in whitening and freckle removal.

[0004] To improve the transdermal performance of tranexamic acid, the existing technology mainly uses liposome encapsulation technology. For example, patent application number CN201811540374.7 discloses a whitening and freckle-removing tranexamic acid flexible liposome, its preparation method, and application. The whitening and freckle-removing tranexamic acid flexible liposome is composed of 0.1% to 6.0% tranexamic acid, 1.0% to 12.0% phospholipids, 0.5% to 5.0% cholesterol, 0.05% to 1% membrane softener, 0.05% to 1.0% ceramide, 0.5% to 3.0% emollient, 5.0% to 15.0% polyol, 0.5% to 2.0% antioxidant, and the balance purified water. The active ingredients in the tranexamic acid flexible liposomes prepared by the present invention have complementary functions and can exert a synergistic effect; the drug loading capacity is large, and active ingredients with different functions such as tranexamic acid can be delivered to the deep layers of the skin, achieving a long-lasting sustained-release effect; the cumulative permeation amount and retention amount of tranexamic acid cream are increased, the defects of gastrointestinal adverse reactions of oral administration are improved, compliance is improved, and patients are easily accepted.

[0005] While this liposome improves the cumulative permeation and retention of tranexamic acid cream to a certain extent, its drug loading is still limited to less than 6% (0.1% to 6.0% tranexamic acid). This insufficient drug loading directly results in a low content of the active ingredient per unit dose of the liposome. Even with improved transdermal efficiency, the absolute amount ultimately delivered to the target site still falls short of meeting clinical whitening and freckle removal requirements, resulting in reduced retention. Furthermore, while the liposome exhibits good stability at room temperature for 30 days, studies have shown that the encapsulation efficiency drops significantly to below 80% after 60 days, with aggregation and delamination occurring. This results in poor stability during long-term storage. These technical limitations severely limit the industrial application of tranexamic acid liposomes.

[0006] Therefore, there is an urgent need to develop a tranexamic acid delivery material with high drug loading, high transdermal efficiency and excellent stability to solve the above problems. Summary of the Invention

[0007] The purpose of the present invention is to provide a tranexamic acid nanoliquid and a preparation method thereof. The preparation method is simple in process. The prepared tranexamic acid nanoliquid can effectively promote the penetration of tranexamic acid through the skin stratum corneum, not only increasing its drug loading capacity, but also effectively increasing the cumulative penetration and retention amount of tranexamic acid cream. It also has good stability under long-term storage, thereby improving its whitening and freckle-removing effects.

[0008] In order to achieve the above-mentioned purpose, the present invention provides the following technical solution: a tranexamic acid nanoliquid, which comprises the following components by mass percentage: 10-30% tranexamic acid, 5-15% lecithin, 5-20% caprylic / capric triglyceride, 9-30% water, glycerol supplemented to 100%, and 0.1-0.5% antioxidant.

[0009] The content of tranexamic acid in the tranexamic acid nanoliquid of the present invention reaches 30%, which increases the drug loading capacity of the prepared nanoliquid. Moreover, through the dual lipid phase structure of lecithin and caprylic / capric triglyceride, a delivery system with a gradient osmotic pressure is formed under the synergistic action of the glycerol hydration layer, an osmotic pressure difference is formed on the skin surface, and tranexamic acid is driven to penetrate the stratum corneum, thereby effectively increasing the drug loading capacity of tranexamic acid, and increasing the content of tranexamic acid in a unit dose of the nanoliquid, the retention amount of tranexamic acid and the cumulative penetration amount, thereby improving its whitening and freckle-removing effect.

[0010] Preferably, the tranexamic acid nanofluid comprises the following components by mass percentage: 30% tranexamic acid, 7% lecithin, 10% caprylic / capric triglyceride, 22.8% water, glycerol supplemented to 100%, and 0.2% antioxidant.

[0011] Preferably, the antioxidant is one or a mixture of tea polyphenols and vitamin E. The addition of the antioxidant can act as a fat-soluble free radical scavenger embedded in the phospholipid bilayer, blocking the oxidation chain reaction. Under the synergistic effect of glycerol, it can effectively improve the antioxidant effect of the prepared nanoliquid, making the prepared nanoliquid more stable and greatly improving the storage stability of the nanoliquid.

[0012] Furthermore, the particle size of the tranexamic acid nanofluid is 60nm-80nm. A particle size of 60nm-80nm can help tranexamic acid penetrate the stratum corneum and reduce aggregation during storage, effectively improving the encapsulation efficiency, retention amount and cumulative permeation amount.

[0013] Furthermore, the encapsulation efficiency of the tranexamic acid nanoliquid after being placed at room temperature for 30 days is 89%-97%, and the encapsulation efficiency of the tranexamic acid nanoliquid after being placed at room temperature for 60 days is 85%-95%.

[0014] Preferably, the lecithin is a mixture of one or more of soybean lecithin, egg yolk lecithin, and hydrogenated lecithin.

[0015] Furthermore, the tranexamic acid nanofluid can be used to prepare skin care products for whitening and removing spots.

[0016] Furthermore, the skin care product comprises 0.5-5% of the tranexamic acid nanofluid, and the dosage form is selected from essence, cream, mask or gel.

[0017] The present invention also provides a method for preparing the tranexamic acid nanofluid as described above, comprising the following steps: (1) Stir water, tranexamic acid, and glycerin to form a uniform aqueous phase; (2) Add lecithin to the aqueous phase, heat it in a water bath, and stir until it dissolves evenly; (3) Add caprylic / capric triglyceride and antioxidant, stir and mix evenly, then cool to room temperature and set aside; (4) The tranexamic acid nanofluidic solution is obtained by microfluidic treatment at a pressure of 1 MPa-2 MPa and cyclic treatment for 3-9 times.

[0018] This preparation method uses microfluidic technology to prepare nanoliquids. By precisely controlling the pressure and number of cycles, nanoliquids with a particle size of 60-80nm can be obtained. This can effectively avoid the destruction of the phospholipid molecular structure, so that the encapsulation rate remains above 85% after 60 days of storage, thereby improving its stability.

[0019] Furthermore, the temperature of the water bath after heating in step (2) is 50°C-65°C.

[0020] Compared with the prior art, the advantages and beneficial effects of the present invention are: 1. The preparation process of the present invention is simple. The prepared tranexamic acid nanofluid forms stable nanovesicles through the dual lipid phase structure of lecithin and caprylic / capric triglyceride under the synergistic effect of the glycerol hydration layer, which significantly increases the tranexamic acid loading to 10-30%, effectively improving the tranexamic acid loading capacity, the tranexamic acid content in the unit dose nanofluid, the retention amount of tranexamic acid and the cumulative permeation amount, thereby improving its whitening and freckle-removing effect; 2. The tranexamic acid nanofluid prepared by the present invention can still maintain an encapsulation efficiency of 85%-95% after standing for 60 days, showing good stability. At the same time, under the antioxidant synergistic effect of vitamin E, the long-term stability of the nanofluid is further ensured, and its storage stability at room temperature is greatly improved, making it suitable for industrial production. 3. In the preparation steps of the present invention, microfluidic technology is used to prepare nanofluidics. By precisely controlling the pressure and the number of cycles, nanofluidics with a particle size of 60 nm to 80 nm can be obtained, which can effectively avoid the destruction of the phospholipid molecular structure, so that the encapsulation efficiency after storage for 60 days is still maintained at more than 85%, thereby improving its stability. DETAILED DESCRIPTION

[0021] The tranexamic acid nanofluid provided by the present invention comprises the following components by mass percentage: 10-30% tranexamic acid, 5-15% lecithin, 5-20% caprylic / capric triglyceride, 9-30% water, glycerol supplemented to a balance of 100%, and 0.1-0.5% antioxidant.

[0022] The present invention provides a method for preparing the above-mentioned tranexamic acid nanoliquid, comprising the following steps: (1) Stir water, tranexamic acid, and glycerin to form a uniform aqueous phase; (2) Add lecithin to the aqueous phase, heat the water bath to 50°C-65°C, and stir to dissolve evenly; (3) Add caprylic / capric triglyceride and antioxidant, stir and mix evenly, then cool to room temperature and set aside; (4) The tranexamic acid nanofluidic solution is obtained by microfluidic treatment at a pressure of 1 MPa-2 MPa and cyclic treatment for 3-9 times.

[0023] The technical solutions of the present invention are described clearly and completely below by way of examples. Obviously, the examples described are only some examples of the present invention, not all of them. All other examples derived by persons of ordinary skill in the art based on the examples of the present invention without inventive effort are intended to fall within the scope of protection of the present invention.

[0024] Example 1 This embodiment provides a method for preparing a tranexamic acid nanoliquid, comprising the following steps: (1) Mix 22.8% water, 30% tranexamic acid, and 30% glycerol at 30-40°C and 200-400 rpm to form a uniform aqueous phase; (2) Add 7% lecithin (specifically soybean lecithin) to the aqueous phase, heat the water bath to 60°C, and stir at 500-800 rpm to dissolve evenly; (3) Add 10% caprylic triglyceride and 0.2% vitamin E, mix well, and cool to room temperature for later use; (4) The solution was then processed by microfluidic technology at a pressure of 1.5 MPa and cycled for 6 times to obtain tranexamic acid nanofluid.

[0025] Example 2 This embodiment provides a method for preparing a tranexamic acid nanoliquid, comprising the following steps: (1) Mix 10% water, 10% tranexamic acid, and 69.9% glycerol at 30-40°C and 200-400 rpm to form a uniform aqueous phase; (2) Add 5% soybean lecithin to the aqueous phase, heat the water bath to 50°C, and stir at 500-800 rpm to dissolve evenly; (3) Add 5% caprylic triglyceride and 0.1% vitamin E, mix well, and cool to room temperature for later use; (4) The solution was then processed by microfluidics at a pressure of 1 MPa and cycled three times to obtain tranexamic acid nanofluid.

[0026] Example 3 This embodiment provides a method for preparing a tranexamic acid nanoliquid, comprising the following steps: (1) Mix 30% water, 20% tranexamic acid, and 14.8% glycerol at 30-40°C and 200-400 rpm to form a uniform aqueous phase; (2) Add 15% soybean lecithin to the aqueous phase, heat the water bath to 65°C, and stir to dissolve evenly; (3) Add 20% caprylic triglyceride and 0.2% vitamin E, stir and mix evenly at 500-800 rpm, then cool to room temperature and set aside; (4) The mixture was then processed using microfluidic technology at a pressure of 2 MPa and cycled for 9 times to obtain tranexamic acid nanofluid.

[0027] Example 4 This embodiment provides a method for preparing a tranexamic acid nanoliquid, comprising the following steps: (1) Mix 22.8% water, 30% tranexamic acid, and 30% glycerol at 30-40°C and 200-400 rpm to form a uniform aqueous phase; (2) Add 7% lecithin to the aqueous phase, heat the water bath to 50°C-65°C, and stir at 500-800 rpm to dissolve evenly; (3) Add 10% capric triglyceride and 0.2% vitamin E, mix well, and cool to room temperature for later use; (4) The solution was then processed by microfluidic technology at a pressure of 1.5 MPa and cycled for 6 times to obtain tranexamic acid nanofluid.

[0028] Example 5 This embodiment provides a method for preparing a tranexamic acid nanoliquid, comprising the following steps: (1) Mix 30% water, 24.8% tranexamic acid, and 10% glycerol at 30-40°C and 200-400 rpm to form a uniform aqueous phase; (2) Add 15% soybean lecithin to the aqueous phase, heat the water bath to 50°C-65°C, and stir at 500-800 rpm to dissolve evenly; (3) Add 20% caprylic triglyceride and 0.2% vitamin E, mix well, and cool to room temperature for later use; (4) The solution was then processed by microfluidic technology at a pressure of 1.8 MPa and cycled for 5 times to obtain tranexamic acid nanofluid.

[0029] Example 6 This embodiment provides a method for preparing a tranexamic acid nanoliquid, comprising the following steps: (1) Mix 9% water, 10% tranexamic acid, and 70% glycerol at 30-40°C and 200-400 rpm to form a uniform aqueous phase; (2) Add 10% soybean lecithin to the aqueous phase, heat the water bath to 50°C-65°C, and stir at 500-800 rpm to dissolve evenly; (3) Add 9.8% caprylic triglyceride and 0.2% vitamin E, mix well, and cool to room temperature for later use; (4) The mixture was then processed by microfluidic technology at a pressure of 2 MPa and cycled four times to obtain tranexamic acid nanofluid.

[0030] Example 7 This embodiment provides a method for preparing a tranexamic acid nanoliquid, comprising the following steps: (1) Mix 30% water, 24.8% tranexamic acid, and 10% glycerol at 30-40°C and 200-400 rpm to form a uniform aqueous phase; (2) Add 15% soybean lecithin to the aqueous phase, heat the water bath to 50°C-65°C, and stir at 500-800 rpm to dissolve evenly; (3) Add 20% capric triglyceride and 0.2% vitamin E, mix well, and cool to room temperature for later use; (4) The mixture was then processed using microfluidic technology at a pressure of 1 MPa and cycled 8 times to obtain tranexamic acid nanofluid.

[0031] Comparative Example 1 This comparative example uses the formula of Example 7 in the comparative document CN201811540374.7 to prepare the nanofluid, and the steps are as follows: (1) Preparation of oil phase: Melt 3.0% hydrogenated lecithin, 9.0% hydroxylated lecithin, 5.0% cholesterol, 0.3% sodium cholate, 0.3% sodium deoxycholate, 0.1% ceramide, 1.0% rosehip oil, and 0.5% jojoba oil in a water bath at 65-80°C, mix well, and set aside; (2) Prepare the aqueous phase: add 6.0% tranexamic acid, 5.0% 1,3-butanediol, 10.0% octyldodecanol, and 0.5% vitamin C glucoside to 59.3% purified water, stir, and heat at 65-80°C to dissolve, and set aside; (3) Preparation of colostrum: Add the oil phase prepared in step (1) dropwise to the water phase prepared in step (2) and stir continuously, then emulsify at 10,000 r / min for 15 min to obtain colostrum; cool to room temperature and set aside; (4) The nanofluidic solution was then processed using microfluidic technology at a pressure of 1.5 MPa and circulated for 6 times to obtain the nanofluid.

[0032] Comparative Example 2 The preparation method of the nanoliquid of this comparative example is as follows: 12% stearyl glyceryl and 10% liquid paraffin are used as the oil phase, which are melted at 80°C; 3% tranexamic acid, 5% glycerol and 70% water are used as the aqueous phase, which are dissolved at 75°C, the two phases are stirred and mixed and emulsified, cooled, and then processed by microfluidic technology to obtain the nanoliquid.

[0033] The specific steps are: (1) Prepare the oil phase: melt 12% stearyl glyceryl, 9.0% hydroxylated lecithin, and 10% liquid paraffin in a water bath at 65-80°C, mix well, and set aside; (2) Prepare the aqueous phase: Add 3% tranexamic acid and 5% glycerol to 70% purified water, stir and heat to 65-80°C to dissolve, and set aside; (3) Preparation of colostrum: Add the oil phase prepared in step (1) dropwise to the water phase prepared in step (2) and stir continuously, and emulsify at a high speed of 10,000 r / min for 15 minutes to obtain colostrum; cool to room temperature and set aside; (4) The nanofluidic solution was then processed using microfluidic technology at a pressure of 1.5 MPa and circulated for 6 times to obtain the nanofluid.

[0034] Experimental Example 1 This experimental example tested the stability of the nanofluids prepared in Examples 1-4 and Comparative Example 1. The method was as follows: after each sample was placed at room temperature for 30 days and 60 days, the particle size and encapsulation efficiency of the sample were checked as well as whether there was agglomeration or stratification. The results are shown in the following table: Table 1 Stability test results of samples prepared in Examples 1-6 and Comparative Example 1

[0035] As can be seen from the above table, the encapsulation efficiency of the tranexamic acid nanoliquids prepared in Examples 1-8 of the present invention after being placed at room temperature for 30 days is 89%-97%, and the encapsulation efficiency after being placed at room temperature for 60 days is 85%-95%; no significant changes were found in the particle size and encapsulation efficiency after being placed at room temperature for 30 days and 60 days, and no agglomeration and stratification occurred at 30 days and 60 days; and although the particle size and encapsulation efficiency of the sample in Comparative Example 1 did not change much at room temperature for 30 days, the particle size and encapsulation efficiency decreased significantly after continuing to stand at room temperature for 30 days, and the sample would agglomerate and stratify after standing at room temperature for 60 days, indicating that the nanoliquid prepared by the present invention has better stability under long-term storage conditions than the nanoliquid prepared in Comparative Example 1.

[0036] Experimental Example 2 The content of tranexamic acid in the nanoliquid was adjusted so that the content of tranexamic acid in the nanoliquids prepared in Examples 1-4 and Comparative Examples 1-2 was the same. Then, mice were used as experimental subjects to study the samples prepared in Examples 1-4 and Comparative Examples 1 and 2. Transdermal experiments were performed on mice to measure the cumulative permeation and retention of tranexamic acid over 12 hours. At the same time, 30 patients with chloasma were selected and the samples prepared in Examples 1-4 and Comparative Examples 1 and 2 were applied to the affected areas daily. The reduction rate of the spot area was measured after 8 weeks. The results are shown in the table below: Table 2 Performance test results of samples prepared in Examples 1-4 and Comparative Example 1

[0037] From the above performance test results, it can be seen that the transdermal effect and whitening and freckle removal efficacy of the nanofluids of Examples 1-8 are significantly better than those of Comparative Examples 1 and 2, especially the comprehensive performance of Example 1 is the most outstanding. This is mainly due to: the high drug loading (30% tranexamic acid) and the dual lipid phase structure (lecithin + caprylic / capric triglyceride) synergistically stabilize the tranexamic acid molecules with the glycerol hydration layer. In addition, under the condition of high drug loading (30% tranexamic acid), by optimizing the ratio of lecithin (5-15%), glycerol (10-70%) and water, a delivery system with a gradient osmotic pressure is formed, forming an osmotic pressure difference on the skin surface, driving tranexamic acid to penetrate the stratum corneum, effectively increasing the cumulative permeation and retention of tranexamic acid, and thus improving the whitening and freckle removal effect.

[0038] Although Comparative Example 1 can improve the performance of tranexamic acid in penetrating the stratum corneum to a certain extent compared with Comparative Example 2, its corresponding cumulative penetration amount and retention amount are still significantly lower than those of Examples 1-8, making its area reduction rate of pigmentation more than 30% lower than that of the examples, indicating that the tranexamic acid nanofluid of the present invention has a better freckle removal effect.

[0039] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A tranexamic acid nano solution, characterized in that: The tranexamic acid nanofluid comprises the following components by mass percentage: 10-30% tranexamic acid, 5-15% lecithin, 5-20% caprylic / capric triglyceride, 9-30% water, glycerol supplemented to 100%, and 0.1-0.5% antioxidant.

2. The tranexamic acid nano solution according to claim 1, characterized in that The tranexamic acid nanofluid comprises the following components by mass percentage: 30% tranexamic acid, 7% lecithin, 10% caprylic / capric triglyceride, 22.8% water, glycerol supplemented to make up to 100%, and 0.2% antioxidant.

3. The tranexamic acid nano solution according to claim 1 or 2, characterized in that The antioxidant is tea polyphenols, vitamin E or a mixture of the two.

4. The tranexamic acid nano solution according to claim 1, characterized in that The particle size of the tranexamic acid nanofluid is 60nm-80nm.

5. The tranexamic acid nanofluid according to claim 1, characterized in that The encapsulation efficiency of the tranexamic acid nanofluid after being placed at room temperature for 30 days is 89%-97%.

6. The tranexamic acid nanofluid according to claim 1, characterized in that The encapsulation efficiency of tranexamic acid nanoparticles after being placed at room temperature for 60 days was 85%-95%.

7. The tranexamic acid nanofluid according to claim 1, characterized in that The lecithin is a mixture of one or more of soybean lecithin, egg yolk lecithin, and hydrogenated lecithin.

8. The tranexamic acid nanofluid according to claim 1, characterized in that The tranexamic acid nanofluid can be used to prepare skin care products for whitening and removing spots.

9. A method for preparing a tranexamic acid nanoliquid according to any one of claims 1 to 7, characterized in that: The following steps are involved: (1) Stir water, tranexamic acid, and glycerin to form a uniform aqueous phase; (2) Add lecithin to the aqueous phase, heat it in a water bath, and stir until it dissolves evenly; (3) Add caprylic / capric triglyceride and antioxidant, stir and mix evenly, then cool to room temperature and set aside; (4) The tranexamic acid nanofluidic solution is obtained by microfluidic treatment at a pressure of 1 MPa-2 MPa and cyclic treatment for 3-9 times.

10. A method for preparing a tranexamic acid nano-liquid, characterized in that: The temperature of the water bath after heating in step (2) is 50°C-65°C.

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