A transamic acid silanol complex and a method for preparing the same

Abstract

The application discloses a citrine silanol complex and a preparation method thereof, and belongs to the technical field of citrine. The preparation method of the citrine silanol complex comprises the following steps: dispersing citrine in an organic solvent containing alkaline water, then adding an organic silicon derivative dropwise, and stirring and reacting to prepare the citrine silanol complex. The citrine silanol complex is formed by combining citrine and an organic active silicon, the complex has excellent affinity, and can significantly enhance the transdermal effect of citrine.

Description

Technical Field

[0001] The present invention relates to the technical field of tranexamic acid, and in particular to a tranexamic acid silanol complex and a preparation method thereof. Background Art

[0002] Tranexamic acid is an amino acid with hemostatic and anti-inflammatory pharmacological effects. It is often used as a coagulation component in medicine. When applied externally, it can inhibit the formation of melanin and prevent the formation of pigment spots, blocking the path of melanin transmission. The whitening mechanism of tranexamic acid is to inhibit the activity of tyrosinase and melanocytes, and prevent melanin aggregation. Therefore, tranexamic acid has good application prospects in the cosmetics field.

[0003] Although tranexamic acid can penetrate into the skin, the penetration rate is slow. Therefore, it is very meaningful to study how to accelerate the transdermal permeability of tranexamic acid. Summary of the Invention

[0004] In order to solve the above-mentioned deficiencies in the prior art, the purpose of the present invention is to provide a tranexamic acid silanol complex and a preparation method thereof, so as to solve the technical problem of the slow penetration of tranexamic acid in the skin.

[0005] The technical solution of the present invention to solve the above technical problems is as follows: providing a tranexamic acid silanol complex, the structural formula of which is shown below:

[0006]

[0007]

[0008] The beneficial effects of the present invention are as follows: tranexamic acid and active organosilicon are mainly combined through hydrogen bonds to form a supramolecular complex, which can enhance the efficacy of the active substance tranexamic acid and also enhance the transdermal permeability of tranexamic acid.

[0009] The preparation method of the tranexamic acid silanol complex comprises the following steps:

[0010] The tranexamic acid is dispersed in an organic solvent containing alkaline water, and then an organosilicon derivative is added dropwise and stirred to react to prepare a tranexamic acid silanol complex.

[0011] On the basis of the above technical solution, the present invention can also be improved as follows:

[0012] Furthermore, the method further comprises: grinding the tranexamic acid to obtain ultrafine tranexamic acid powder, and then dispersing the powder in an organic solvent containing alkaline water.

[0013] Furthermore, the mesh size of the tranexamic acid ultrafine powder is 100-2000 mesh.

[0014] Furthermore, the organic solvent is at least one of ethyl acetate, chloroform, dichloromethane, petroleum ether, diethyl ether and methyl tert-butyl ether.

[0015] Furthermore, the alkaline water is an alkaline aqueous solution with a pH of 7-8, preferably the alkaline water is an alkaline aqueous solution with a pH of 7.6, and more preferably the alkaline water is a sodium bicarbonate aqueous solution with a pH of 7.6.

[0016] Furthermore, the acidic water is an acidic aqueous solution with a pH of 4-6, preferably the acidic water is an acidic aqueous solution with a pH of 5, and more preferably the acidic water is a hydrochloric acid aqueous solution with a pH of 5.

[0017] Furthermore, the weight of the organosilicon derivative is 0.1-5% of the weight of the tranexamic acid.

[0018] Furthermore, the organosilicon derivative is at least one of trichloromethylsilane, bis(dimethylamino)dimethylsilane, dimethylchlorosilane and dimethyldichlorosilane.

[0019] Furthermore, during the stirring reaction, the stirring speed is 10-200 r / min, the reaction temperature is 20-60° C., and the reaction time is 1-20 h.

[0020] Furthermore, the method further comprises: after the stirring reaction is completed, centrifuging the reaction product and vacuum drying it to obtain a tranexamic acid silanol complex.

[0021] Furthermore, the vacuum drying conditions are: temperature 30-70° C., vacuum degree 100-20,000 Pa.

[0022] The present invention has the following beneficial effects:

[0023] Tranexamic acid and organic active silicon are combined to form a tranexamic acid silanol complex, which has excellent affinity and can significantly enhance the transdermal effect of tranexamic acid. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is the H NMR spectrum of tranexamic acid silanol complex.

[0025] Figure 2 This is the carbon NMR spectrum of tranexamic acid silanol complex.

[0026] Figure 3 The image shows the distribution of 2% tranexamic acid at different depths of the skin with different penetration times.

[0027] Figure 4 The image shows the distribution of tranexamic acid in a 2% tranexamic acid silanol complex at different depths of the skin with different penetration times. DETAILED DESCRIPTION

[0028] The following examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention. In the examples, where specific conditions are not specified, the experiments were performed under conventional conditions or those recommended by the manufacturer. Reagents or instruments used, where the manufacturer is not specified, are commercially available conventional products.

[0029] Example 1:

[0030] A method for preparing a tranexamic acid silanol complex comprises the following steps:

[0031] 10g of tranexamic acid was weighed, ground in a ball mill, and then passed through a 2000-mesh sieve to obtain a 2000-mesh ultrafine tranexamic acid powder. The ultrafine tranexamic acid powder was placed in 100mL of dichloromethane containing a trace amount of alkaline water (alkaline water is a sodium bicarbonate aqueous solution with a pH of 7.6, with a volume of 0.3mL), stirred and dispersed evenly, and then 0.15mL of trichloromethylsilane was added dropwise, the temperature was maintained at 20°C, stirring was continued for 1h, and then centrifuged and filtered at 500r / min using a conventional centrifuge to obtain a tranexamic acid silanol complex. The tranexamic acid silanol complex was then spread out in the air and placed in a vacuum drying oven, maintained at 30°C and a vacuum degree of 100 Pa, to finally obtain 8g of the tranexamic acid silanol complex.

[0032] In this example, when preparing the tranexamic acid silanol complex, the chlorine and other elements contained in the organosilicon reacted with a trace amount of alkaline water to form sodium chloride, which then entered the organic layer solvent layer containing a trace amount of water. The structural formula of the tranexamic acid silanol complex finally obtained is shown below:

[0033]

[0034] The H NMR spectrum of the tranexamic acid silanol complex is shown in Figure 1 , the C NMR spectrum is shown in Figure 2 , its specific NMR data are as follows:

[0035] H NMR spectrum: 1 H-NMR: δ: 2.40(2H),2.02(1H),1.79(2H),1.69(2H),1.43(1H),1.16(2H),0.85(2H),0.07(Si-C H3 ). C NMR spectrum: 13 C-NMR: δ: 176.8, 44.4, 42.3, 35.1, 29.0, 29.0, 28.2, 28.2, 0.72 (Si- C H3). Through the H-NMR and C-NMR spectra, we can see the NMR data of tranexamic acid and the silicon methyl signals in silanol.

[0036] Example 2:

[0037] A method for preparing a tranexamic acid silanol complex comprises the following steps:

[0038] 50g of tranexamic acid was weighed, ground in a ball mill, and then passed through a 100-mesh sieve to obtain a 100-mesh ultrafine tranexamic acid powder. The ultrafine tranexamic acid powder was placed in 500mL of ether containing a trace amount of alkaline water (alkaline water is a sodium bicarbonate aqueous solution with a pH of 7.6, with a volume of 2mL), stirred and dispersed uniformly, and then 3mL of dimethylchlorosilane was added dropwise, the temperature was maintained at 60°C, and stirring was continued for 20h. Then, a conventional centrifuge was used for centrifugal filtration at 5000r / min to obtain a tranexamic acid silanol complex. The tranexamic acid silanol complex was then spread out in the air and placed in a vacuum drying oven, maintained at 70°C and a vacuum degree of 20,000 Pa, to finally obtain 38g of the tranexamic acid silanol complex.

[0039] The structural formula of the tranexamic acid silanol complex prepared above is as follows:

[0040]

[0041] Its H NMR spectrum: 1 H-NMR: δ: 2.40(2H),2.02(1H),1.79(2H),1.70(2H),1.43(1H),1.16(2H),0.85(2H),0.05(Si-C H3 ). C NMR spectrum: 13 C-NMR: δ: 176.5, 44.6, 42.3, 35.1, 29.0, 29.0, 28.2, 28.2, 0.63 (Si- C H3). Through the H-NMR and C-NMR spectra, we can see the NMR data of tranexamic acid and the silicon methyl signals in silanol.

[0042] Example 3:

[0043] A method for preparing a tranexamic acid silanol complex comprises the following steps:

[0044] 500g of tranexamic acid was weighed, placed in a ball mill and ground, and then passed through a 500-mesh sieve to obtain a 500-mesh ultrafine tranexamic acid powder. The ultrafine tranexamic acid powder was placed in 5000mL of ether containing a trace amount of acidic water (acidic water is a hydrochloric acid aqueous solution with a pH of 5, with a volume of 15mL), stirred and dispersed uniformly, and then 25mL of bis(dimethylamino)dimethylsilane was added dropwise, the temperature was maintained at 45°C, and stirring was continued for 6h. Then, a conventional centrifuge was used for centrifugal filtration at 2000r / min to obtain a tranexamic acid silanol complex. The tranexamic acid silanol complex was then spread out in the air and placed in a vacuum drying oven, maintained at 50°C and a vacuum degree of 5000 Pa, to finally obtain 410g of the tranexamic acid silanol complex.

[0045] The structural formula of the tranexamic acid silanol complex prepared above is as follows:

[0046]

[0047] Its H NMR spectrum: 1 H-NMR: δ: 2.41(2H),2.02(1H),1.79(2H),1.69(2H),1.43(1H),1.16(2H),0.85(2H),0.06(Si-C H3 ). C NMR spectrum: 13 C-NMR: δ: 176.7, 44.5, 42.3, 35.0, 29.1, 29.1, 28.3, 28.3, 0.70 (Si- C H3). Through the H-NMR and C-NMR spectra, we can see the NMR data of tranexamic acid and the silicon methyl signals in silanol.

[0048] The functions of the silanol complexes of succinic acid prepared in Examples 1-3 are basically the same. Taking Example 1 as an example, the following test process and results are given:

[0049] 1. The human body (in vivo) non-invasive Raman optical testing method was used to test the permeability of the tranexamic acid silanol complex (also known as ultra-sensitive tranexamic acid U-Sorb TXA) in Example 1 during human use. The specific process is as follows:

[0050] (1) Testing process

[0051] The test was conducted on subjects. After their visit, they cleansed the test area with water and then sat quietly in a constant temperature and humidity chamber for 30 minutes. During this time, they selected two test areas, one on each inner arm (Test Area A) and one on each inner arm (Test Area B), each measuring 2 x 2 cm². After 30 minutes, 2% tranexamic acid was applied to Test Area A, and 2% tranexamic acid silanol complex was applied to Test Area B. In vivo Raman measurements were performed using a LabRAM Odyssey high-speed, high-resolution confocal Raman microscope (HORIBA) 0.5, 1, and 2 hours after application. The ambient temperature was 22°C ± 2°C and the humidity was 50% ± 10% RH. The results were then compared to determine the relative penetration rate of the active ingredient after application with 2% tranexamic acid and 2% tranexamic acid silanol complex.

[0052] (2) Test results and data processing

[0053] Raman spectroscopy imaging data processing includes spectral preprocessing and data analysis. Spectral preprocessing includes cosmic ray removal, spectral smoothing, background noise removal, baseline calibration, and spectral normalization. Univariate data analysis primarily analyzes the Raman spectral data for biochemical substances corresponding to specific peak positions, revealing the distribution of these substances within human skin.

[0054] Data analysis Labspec5 software was used to perform baseline calibration of the Raman spectrum and confirm the position of the characteristic peaks. The obtained Raman spectra were calculated, including peak intensity, peak shift, peak area, half-peak width, etc.; Labspec6 software was also used to perform numerical analysis of the peak intensities corresponding to different depths and to plot their spatial distribution.

[0055] The permeability behavior of a product is determined by using its characteristic Raman signal, which is different from the intrinsic signal of the skin, to confirm its distribution at different skin depths. The relative permeability is calculated as follows:

[0056] Relative permeability (%) = standard deviation (test value before use of the test product - test value after use of the test product) * 100%.

[0057] The distribution images of tranexamic acid in 2% tranexamic acid and 2% tranexamic acid silanol complex at different depths of the skin with different penetration times are shown in Figure 2. Figure 3 and Figure 4 .Depend on Figure 3 It can be seen that when using 2% tranexamic acid, tranexamic acid did not penetrate into the stratum corneum within 0.5 hours; it quickly penetrated into the stratum corneum within 1 hour; and it broke through the stratum corneum and entered the active epidermis within 2 hours, but did not penetrate into the dermis. Figure 4It can be seen that when using 2% tranexamic acid silanol complex, tranexamic acid quickly penetrates into the stratum corneum within 0.5 hours; breaks through the stratum corneum and enters the active epidermis within 1 hour; and continues to penetrate into the active epidermis within 2 hours.

[0058] Through calculation, the relative permeability of tranexamic acid in each measurement area at different time points was obtained, and the results were: 0.5h, 1h, and 2h after using 2% tranexamic acid on human skin, the relative permeability of tranexamic acid (tracing tranexamic acid) was 0.00%, 0.61% and 2.01% respectively; 0.5h, 1h, and 2h after using 2% tranexamic acid silanol complex on human skin, the relative permeability of tranexamic acid (tracing tranexamic acid) was 0.76%, 2.31% and 3.41% respectively.

[0059] From the above-mentioned human skin in vivo experimental results, it can be seen that tranexamic acid silanol complex with the same concentration can penetrate the skin more quickly than tranexamic acid.

[0060] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A tranexamic acid silanol complex, characterized in that: The structural formula is shown below:

2. The method for preparing the tranexamic acid silanol complex according to claim 1, wherein: The following steps are involved: The tranexamic acid is dispersed in an organic solvent containing alkaline water or acidic water, and then an organosilicon derivative is added dropwise and stirred for reaction to prepare a tranexamic acid silanol complex.

3. The method for preparing the tranexamic acid silanol complex according to claim 2, wherein: Also includes: Tranexamic acid is ground into powder to obtain ultrafine tranexamic acid powder, which is then dispersed in an organic solvent containing alkaline water.

4. The method for preparing the tranexamic acid silanol complex according to claim 2 or 3, wherein: The organic solvent is at least one of ethyl acetate, chloroform, dichloromethane, petroleum ether, ethyl ether and methyl tert-butyl ether; the alkaline water is an alkaline aqueous solution with a pH of 7-8; and the acidic water is an acidic aqueous solution with a pH of 4-6.

5. The method for preparing the tranexamic acid silanol complex according to claim 2, wherein: The weight of the organosilicon derivative is 0.1-5% of the weight of the tranexamic acid.

6. The method for preparing a tranexamic acid silanol complex according to claim 2 or 5, wherein: The organosilicon derivative is at least one of trichloromethylsilane, bis(dimethylamino)dimethylsilane, dimethylchlorosilane and dimethyldichlorosilane.

7. The method for preparing the tranexamic acid silanol complex according to claim 2, wherein: During the stirring reaction, the stirring speed is 10-200 r / min, the reaction temperature is 20-60° C., and the reaction time is 1-20 h.

8. The method for preparing the tranexamic acid silanol complex according to claim 2, wherein: Also includes: After the stirring reaction is completed, the reaction product is centrifuged and vacuum dried to obtain a tranexamic acid silanol complex.

9. The method for preparing the tranexamic acid silanol complex according to claim 8, wherein: The vacuum drying conditions are: temperature 30-70°C, vacuum degree 100-20000 Pa.

10. Use of the tranexamic acid silanol complex according to claim 1 in the preparation of cosmetics.

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