Particles loaded with cosmetic active ingredients, preparation method and application

Abstract

The present invention belongs to the field of new daily chemical materials and specifically relates to particles loaded with cosmetic active ingredients, comprising platinum particles and the cosmetic active ingredient physically or chemically bonded to the surface of the platinum particles. After loading the particles with the cosmetic active ingredient, they can further enhance the skincare benefits of the active ingredient, including but not limited to moisturizing, anti-wrinkle, whitening, and antioxidant properties. A second object of the present invention is to provide a preparation method and application of these particles.

Description

Technical Field

[0001] The present invention belongs to the field of new daily chemical materials, and in particular relates to particles loaded with cosmetic active ingredients, a preparation method and applications. Background Art

[0002] Noble metal nanoparticles are particles formed by stacking a certain number of noble metal atoms, such as Au, Ag, and Pt. Particle shapes can vary, including spheres, rods, flowers, and cubes, with spheres being the most commonly used. Similarly, by manipulating the number of stacked atoms, particles of varying sizes can be obtained.

[0003] Precious metal particles themselves can serve as carrier matrices, combining with biomolecules (e.g., nucleic acids, antibodies, peptides, proteins), drug molecules, fluorescent substances, polymers, etc. to form microparticles with monolithic properties. These particles are widely used in the biomedical field. However, this technology has been rarely applied in the cosmetics field.

[0004] The applicant has filed patent application CN106963658A, which discloses a cosmetic composition containing nano-platinum. Experiments have demonstrated that nano-platinum can eliminate all active oxygen species in the body and maintain its effects within the body. Furthermore, nano-platinum is colorless and odorless, and is considered safe and harmless for use as an active ingredient in cosmetics.

[0005] In addition, for the application of platinum in daily chemical products, you can also refer to: CN106420445B, which discloses a skin care matrix with moisturizing and antioxidant effects, as well as its preparation method and application. The matrix uses 2nm platinum particles and multiple active ingredients to form a composition.

[0006] In further research on nano-platinum, we found that this material has even greater potential in cosmetics. Summary of the Invention

[0007] In response to the shortcomings of the prior art, the first object of the present invention is to provide particles loaded with cosmetic active ingredients. After loading the particles with the cosmetic active ingredients, they can further enhance the skin care functions of the active ingredients, including but not limited to moisturizing, anti-wrinkle, whitening, and anti-oxidation.

[0008] The second object of the present invention is to provide a preparation method and application based on the above particles.

[0009] In order to achieve the first object of the invention, the present invention adopts the following technical solutions:

[0010] A particle loaded with a cosmetic active ingredient comprises a platinum particle and the cosmetic active ingredient connected to the surface of the platinum particle by physical action or chemical bond.

[0011] In the above particles, the particle size of the platinum is 3-200 nm.

[0012] The particle size of the platinum is 3 nm, 5 nm, 10 nm, 20 nm, 30 nm, 40 nm, 50 nm, 100 nm, 120 nm, 150 nm, 180 nm or 200 nm;

[0013] In the above particles, the physical effect is electrostatic effect, van der Waals force, hydrogen bond effect, and hydrophobic effect; and the chemical bond is a covalent bond, a coordination bond, or a dangling bond.

[0014] In the above-mentioned particles, the cosmetic active ingredients include one or more of fat-soluble active ingredients, water-soluble active ingredients, active ingredients with a molecular weight greater than 5000, and polypeptides.

[0015] In the above-mentioned particles, the fat-soluble active ingredient is one or more of glabridin, ceramide, resveratrol, and salicylic acid;

[0016] The water-soluble active ingredient is one or more of madecassoside, tetrahydropyrimidine carboxylic acid, dipotassium glycyrrhizate, nicotinamide, and ascorbic acid;

[0017] The active ingredient with a molecular weight greater than 5000 is one or more of oligomeric sodium hyaluronate (molecular weight of 5-10 kDa), medium molecular weight sodium hyaluronate (molecular weight of 800,000-1.5 million Da), high molecular weight sodium hyaluronate (>1.8 million Da), β-glucan, sodium acetyl hyaluronate, and sodium heparin;

[0018] The polypeptide is one or more of palmitoyl tripeptide-5, hexapeptide-11, hexapeptide-9, carnosine, acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-1, palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, nonapeptide-1, acetyl tetrapeptide-2, and tetrapeptide-1.

[0019] In the above particles, the weight ratio of the platinum particles to the cosmetic active ingredient is 1:0.1-20.

[0020] The weight ratio of platinum to the cosmetic active ingredient is 1:0.1, 1:0.5, 1:1, 1:2, 1:5, 1:10, 1:15, and 1:20.

[0021] At the same time, the present invention also discloses a method for preparing the above particles, comprising the following steps:

[0022] Step 1: Prepare platinum particles;

[0023] Step 2: exchange the surface ligand molecules of the platinum particles and bind diethylamine;

[0024] Step 3: Mixing the treated platinum particles with the cosmetic active ingredient so that the cosmetic active ingredient is connected to the surface of the platinum particles.

[0025] In the above preparation method, the step 1 is specifically:

[0026] When the ascorbic acid and PVP aqueous solutions are heated to boiling, potassium tetrachloroplatinate solution is injected into the reaction system to maintain the reaction to obtain a reaction product; the reaction product is then precipitated and separated using acetone as a precipitant to obtain platinum particles.

[0027] In the above preparation method, the step 2 is specifically:

[0028] Platinum particles and diethylamine are mixed and stirred to obtain diethylamine-loaded platinum particles, so that the PVP attached to the surface of the platinum particles is detached and attached to the diethylamine;

[0029] placing the diethylamine-loaded platinum particles in an acidic solution to release the diethylamine from the surface of the platinum particles and collecting the platinum particles from which the diethylamine has been released;

[0030] The platinum particles freed from diethylamine are reacted with a solution containing a cosmetic active ingredient to obtain particles loaded with the cosmetic active ingredient.

[0031] Finally, the present invention also discloses the use of the particles described above in preparing cosmetics.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] 1. The carrier of the present invention uses platinum particles to load cosmetic active ingredients. The platinum particles improve the stability of the cosmetic active ingredients, achieve rapid delivery, and activate the cosmetic active ingredients, allowing the cosmetic active ingredients to achieve higher performance with a lower dosage. Furthermore, loading experiments on different cosmetic active ingredients have confirmed that the platinum particles have good delivery and activation effects for most cosmetic active ingredients.

[0034] 2. Platinum particles themselves have a strong catalytic effect, reducing reactive oxygen species in vivo and protecting cells and tissues. By modifying the surface of platinum particles with cosmetic active ingredients, the biorecognition and absorption efficiency of platinum particles by cells are enhanced, further enhancing the beneficial effects of platinum particles on the skin. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1A is the particle size distribution diagram of Example 1;

[0036] Figure 1B is the particle size distribution diagram of Example 2;

[0037] Figure 1C is the particle size distribution diagram of Example 3;

[0038] Figure 2 Comparison of infrared spectra of platinum particles loaded with glabridin; Pt-PVP represents PVP-modified Pt particles; glabridin represents glabridin; Pt-glabridin represents glabridin-modified Pt particles;

[0039] Figure 3 Comparison of infrared spectra of platinum particles loaded with madecassoside; Pt-PVP represents PVP-modified Pt particles; madecassoside represents madecassoside; Pt-madecassoside represents madecassoside-modified Pt particles;

[0040] Figure 4 This is the infrared spectrum of platinum particles loaded with madecassoside;

[0041] Figure 5 The infrared spectra of platinum particles loaded with different molecular weights of sodium hyaluronate are compared; Pt-PVP represents Pt particles modified with PVP; HA represents sodium hyaluronate; Pt-HA represents Pt particles modified with sodium hyaluronate glycoside; HMW represents high molecular weight; MMW represents medium molecular weight; LMW represents low molecular weight;

[0042] Figure 6 Comparison of infrared spectra of platinum particles loaded with palmitoyl tripeptide-5; Pt-PVP represents Pt particles modified with PVP; Palmitoyl tripeptide-5 represents palmitoyl tripeptide-5; Pt-PTP5 represents Pt particles modified with palmitoyl tripeptide-5 glycoside;

[0043] Figure 7A This is a diagram showing the solubility results of the sample loaded with glabridin and the sample not loaded with glabridin;

[0044] Figure 7B Solubility results of samples loaded with palmitoyl tripeptide-5 and samples not loaded with palmitoyl tripeptide-5;

[0045] Figure 7C The graph shows the solubility results of ceramide-loaded and non-ceramide-loaded samples. DETAILED DESCRIPTION

[0046] The technical solution of the present invention is further described below by way of specific embodiments. It should be understood by those skilled in the art that the embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0047] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in this field can be used. If the manufacturer of the reagents or instruments is not specified, they are all commercially available conventional reagents.

[0048] Part I: Preparation of Platinum Particles

[0049] Example 1

[0050] Step 1: Preparation of 20nm platinum particles:

[0051] The prescribed amounts of ascorbic acid aqueous solution, potassium tetrachloroplatinate aqueous solution and PVP aqueous solution were prepared respectively.

[0052] Ascorbic acid and PVP aqueous solution were placed in a three-necked flask equipped with a reflux tube. When the solution was heated to boiling, potassium tetrachloroplatinate solution was quickly injected into the reaction system and the reaction was maintained for 1 hour.

[0053] The specific ratio is shown in Table 1;

[0054] Step 2: Purification of platinum particles: Use acetone as a precipitant, mix with the platinum particle aqueous dispersion from step 1, and centrifuge at 6000 rpm for 5 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0055] Since the platinum particles are insoluble in acetone, they form a precipitate. The supernatant is removed, and the precipitate is retained. An appropriate amount of PVP aqueous solution is added to the resulting precipitate and dispersed until uniform, yielding an aqueous dispersion of platinum particles. This process is repeated three times. Finally, the solution is diluted with pure water to a platinum content of 1000 ppm, yielding a 20 nm platinum particle solution.

[0056] Example 2

[0057] Step 1: Preparation of 100 nm platinum particles:

[0058] Prepare the prescribed amounts of ascorbic acid aqueous solution, potassium tetrachloroplatinate aqueous solution, potassium iodide aqueous solution, and PVP aqueous solution. Place the ascorbic acid, potassium iodide, PVP aqueous solution, and 20 μL of the platinum particle solution from Example 1 in a three-necked flask equipped with a reflux tube. Heat the solution to 90°C. Slowly add the potassium tetrachloroplatinate solution dropwise to the reaction system and maintain the reaction for 1 hour.

[0059] The specific ratio is shown in Table 1;

[0060] Step 2: Purification of platinum particles: Use acetone as a precipitant, mix with the platinum particle aqueous dispersion from step 1, and centrifuge at 6000 rpm for 5 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0061] Since the platinum particles are insoluble in acetone, they form a precipitate. The supernatant is removed, and the precipitate is retained. An appropriate amount of PVP aqueous solution is added to the resulting precipitate and dispersed until uniform, yielding an aqueous dispersion of platinum particles. This process is repeated three times. Finally, the solution is diluted with pure water to a platinum content of 1000 ppm, yielding a 100 nm platinum particle solution.

[0062] Example 3

[0063] Step 1: Preparation of 200 nm platinum particles:

[0064] Prepare the prescribed amounts of ascorbic acid aqueous solution, potassium tetrachloroplatinate aqueous solution, potassium iodide aqueous solution, and PVP aqueous solution. Place the ascorbic acid, potassium iodide, PVP aqueous solution, and 10 μL of the platinum particle solution from Example 1 in a three-necked flask equipped with a reflux tube. Heat the solution to 80°C. Slowly add the potassium tetrachloroplatinate solution dropwise to the reaction system and maintain the reaction for 2 hours.

[0065] The specific ratio is shown in Table 1;

[0066] Step 2: Purification of platinum particles: Use acetone as a precipitant, mix with the platinum particle aqueous dispersion from step 1, and centrifuge at 6000 rpm for 5 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0067] Since the platinum particles are insoluble in acetone, they form a precipitate. The supernatant is removed, and the precipitate is retained. An appropriate amount of PVP aqueous solution is added to the resulting precipitate and dispersed until uniform, yielding an aqueous dispersion of platinum particles. This process is repeated three times. Finally, the solution is diluted with pure water to a platinum content of 1000 ppm, yielding a 200 nm platinum particle solution.

[0068] Table 1 Platinum particle synthesis prescription

[0069]

[0070]

[0071] Part 2 Active ingredient loading

[0072] Example 4

[0073] The product of Example 1 was loaded with glabridin, and finished products 1, 2, and 3 were prepared according to the loading amount;

[0074] Step 1: Take 1 ml of the platinum particle solution from Example 1 (platinum particle concentration: 1000 ppm), add 1 / 10 volume of diethylamine, and slowly stir at room temperature for 24 hours. Add an appropriate amount of the mixture to acetone and centrifuge at 8000 rpm for 3 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0075] The function of diethylamine is to separate the platinum particles and PVP through competitive binding and to connect diethylamine to the surface of the platinum particles;

[0076] Step 2: After centrifugation, remove the supernatant and retain the precipitate. Add 2 ml of 20% acetic acid aqueous solution to the precipitate and disperse it until uniform, obtaining a platinum particle dispersion.

[0077] The function of the acetic acid is to neutralize the diethylamine to weaken the binding force between the diethylamine and the platinum particles, so that the platinum particles obtained in step 3 are platinum particles without any loading substances;

[0078] Step 3: Mix the platinum particle dispersion from step 2 with acetone and centrifuge at 8000 rpm for 3 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0079] Step 4: After centrifugation, remove the supernatant and retain the pellet.

[0080] 1 ml of 1000 / 2500 / 5000 ppm glabridin ethanol solution (100% ethanol solution) was added to the obtained precipitate, and dispersed until uniform, to obtain ethanol solutions of platinum particles loaded with different contents of glabridin, which were finished products 1, 2, and 3, respectively.

[0081] Example 5

[0082] The product of Example 2 was used to load madecassoside, and finished products 4, 5, and 6 were prepared according to the loading amount;

[0083] Step 1: Take 1 ml of the platinum particle solution from Example 2 (platinum particle concentration: 1000 ppm), add 1 / 10 volume of diethylamine, and slowly stir at room temperature for 24 hours. Add an appropriate amount of the mixture to acetone and centrifuge at 8000 rpm for 3 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0084] Step 2: After centrifugation, remove the supernatant and retain the precipitate. Add 2 ml of 20% acetic acid aqueous solution to the precipitate and disperse it until uniform, obtaining a platinum particle dispersion.

[0085] Step 3: Mix an appropriate amount of the platinum particle dispersion from step 2 with acetone and centrifuge at 8000 rpm for 3 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0086] Step 4: After centrifugation, remove the supernatant and retain the pellet.

[0087] 1 ml of 1000 / 2500 / 5000 ppm madecassoside aqueous solution was added to the obtained precipitate, and dispersed until uniform, to obtain aqueous solutions of platinum particles loaded with different contents of madecassoside, which were respectively Finished Product 4, Finished Product 5, and Finished Product 6.

[0088] Example 6

[0089] The product of Example 3 was used to load hyaluronic acid, and finished products 7, 8, and 9 were prepared according to the loading amount;

[0090] Step 1: Take 1 ml of the platinum particle solution from Example 3 (platinum particle concentration: 1000 ppm), add 1 / 10 volume of diethylamine, and slowly stir at room temperature for 24 hours. Add an appropriate amount of the mixture to acetone and centrifuge at 8000 rpm for 3 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0091] Step 2: After centrifugation, remove the supernatant and retain the precipitate. Add 2 ml of 20% acetic acid aqueous solution to the precipitate and disperse it until uniform, obtaining a platinum particle dispersion.

[0092] Step 3: Mix an appropriate amount of the platinum particle dispersion from step 2 with acetone and centrifuge at 8000 rpm for 3 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0093] Step 4: After centrifugation, the supernatant was removed and the precipitate was retained. 1 ml of 1000 / 2500 / 5000 ppm aqueous solutions of oligomeric sodium hyaluronate (molecular weight 5-8 kDa) was added to the resulting precipitate and dispersed uniformly to obtain aqueous solutions loaded with hyaluronic acid platinum particles at different concentrations, namely Finished Product 7, Finished Product 8, and Finished Product 9.

[0094] Example 7

[0095] The product of Example 1 was used to load palmitoyl tripeptide-5, and finished products 10, 11, and 12 were prepared according to the loading amount;

[0096] Step 1: Take 1 ml of the platinum particle solution from Example 1 (platinum particle concentration: 1000 ppm), add 1 / 10 volume of diethylamine, and slowly stir at room temperature for 24 hours. Add an appropriate amount of the mixture to acetone and centrifuge at 8000 rpm for 3 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0097] Step 2: After centrifugation, remove the supernatant and retain the precipitate. Add 2 ml of 20% acetic acid aqueous solution to the precipitate and disperse it until uniform, obtaining a platinum particle dispersion.

[0098] Step 3: Mix an appropriate amount of the platinum particle dispersion from step 2 with acetone and centrifuge at 8000 rpm for 3 minutes. The weight ratio of acetone to platinum particles is 3000:1.

[0099] Step 4: After centrifugation, the supernatant was removed and the precipitate was retained. 1 ml of 1000 / 2500 / 5000 ppm palmitoyl tripeptide-5 ethanol solution (100% ethanol solution) was added to the resulting precipitate and dispersed until uniform, obtaining ethanol solutions loaded with different contents of palmitoyl tripeptide-5 platinum particles, namely Finished Product 10, Finished Product 11, and Finished Product 12.

[0100] Part 4 Preparation of comparative samples

[0101] Comparative Example 1

[0102] The glabridin powder was dissolved in a mixed solvent of 30% by mass of butanediol and water to make the concentration of glabridin be 100 ppm, thereby obtaining a comparative sample 1.

[0103] Comparative Example 2

[0104] The platinum particle dispersion and glabridin powder of Example 1 were added to a mixed solvent of 30% by mass of butanediol and water, so that the concentrations of the platinum particles and glabridin were both 100 ppm, to obtain comparative sample 2.

[0105] Comparative Example 3

[0106] Madecassoside powder was dissolved in a mixed solvent of 30% by mass of butanediol and water to make the concentration of madecassoside 250 ppm, to obtain comparative sample 3.

[0107] Comparative Example 4

[0108] The platinum particle dispersion and madecassoside powder of Example 2 were added to a mixed solvent of 30% by mass of butanediol and water to make the concentration of platinum particles 100 ppm and madecassoside 250 ppm, to obtain comparative sample 4.

[0109] Comparative Example 5

[0110] The oligomeric sodium hyaluronate powder was dissolved in a mixed solvent of 30% by mass of butanediol and water to make the concentration of the oligomeric sodium hyaluronate 500 ppm, thereby obtaining comparative sample 5.

[0111] Comparative Example 6

[0112] The platinum particle dispersion and oligomeric sodium hyaluronate powder of Example 3 were added to a mixed solvent of 30% by mass of butanediol and water, so that the concentration of the platinum particles was 100 ppm and the concentration of the oligomeric sodium hyaluronate was 500 ppm, to obtain comparative sample 6.

[0113] Comparative Example 7

[0114] Palmitoyl tripeptide-5 powder was dissolved in ethanol to obtain a comparative sample 7.

[0115] Comparative Example 8

[0116] The platinum particle dispersion and palmitoyl tripeptide-5 powder of Example 1 were added to ethanol so that the concentrations of the platinum particles and palmitoyl tripeptide-5 were both 100 ppm, to obtain comparative sample 8.

[0117] Part V Physical and Chemical Performance Test

[0118] 1. Particle size test of platinum particles of different sizes

[0119] Dynamic Light Scattering (DLS): Before testing, the sample was diluted to 1% with pure water and sonicated for 2 minutes. The dilution was then placed in a sample cell. The average particle size (in nanometers), polydispersity index (PDI), and zeta potential (in mV) of the sample were measured using a Malvern Zetasizer Advance instrument.

[0120] The particle size distribution of Examples 1-3 can be referred to Figures 1A to 1C ;

[0121] The particle size statistics and polydispersity coefficient results can be found in Table 2;

[0122] Table 2 Particle size statistics, polydispersity coefficient and zeta potential results of platinum particles of different sizes

[0123] Group Example 1 Example 2 Example 3 Particle size (nm) 22.58±0.49 105.2±1.82 200.1±0.07 PDI 0.28±0.03 0.02±0.01 0.09±0.07 Zeta potential (mV) －3.72 －0.71 －1.13

[0124] As can be seen from Table 2, Examples 1-3 of the present invention all prepared platinum particles with desired particle sizes.

[0125] Table 3 Particle size statistics, polydispersity coefficient and zeta potential of platinum particles of different sizes loaded with active substances

[0126]

[0127] As can be seen from Table 3, the particle size of samples 1 to 12 did not change significantly after loading the active ingredient, but the Zeta potential did change significantly. From the perspective of Zeta potential, it can be proved that the platinum particles of the present invention have successfully loaded the active ingredient.

[0128] 2. Infrared spectra before and after loading active substances

[0129] Sample pretreatment: The samples of the examples were centrifuged using an antisolvent (i.e., a solvent in which the active substance is insoluble. For example, glabridin corresponds to water; madecassoside corresponds to tetrahydrofuran; sodium hyaluronate corresponds to acetone; and palmitoyl tripeptide-5 corresponds to water). Centrifuge at 8000 rpm for 10 minutes, discard the supernatant, and retain the precipitate. Re-disperse using a solvent in which the active substance is soluble, repeatedly add the antisolvent for centrifugal precipitation, repeat twice, and collect the precipitate. The purpose of multiple washings is to remove the active substance not loaded by the platinum particles.

[0130] Infrared spectroscopy: An appropriate amount of sample powder was mixed with potassium bromide and ground into a fine powder. The ground powder was pressed into a thin sheet using a hydraulic press. The infrared spectrum of the sample was measured using a Thermo Scientific Nicolte iS50 Fourier transform infrared spectrometer in transmission mode.

[0131] The test results can be referred to Figures 2 to 6;

[0132] Figure 2 From the spectrum, we can see that 500cm -1 ~1500cm -1 Interval, 2900cm -1 , 3300cm -1 and 3500cm -1 Nearby is the characteristic infrared absorption peak of the glabridin molecular group. Platinum particles themselves do not have characteristic peaks in this range, but after surface modification and loading with glabridin, characteristic peaks in this range appear, indicating that the platinum particles are successfully loaded with glabridin molecules.

[0133] Figure 3 and 4 From the spectrum, we can see that the group of hydroxy-madecassoside molecule is at 1000cm -1 There is significant infrared absorption near 1000cm -1 There is absorption nearby, indicating successful binding with madecassoside molecules.

[0134] Figure 5 From the spectrum, we can see that 1000cm -1 ~1700cm -1 The range represents the characteristic infrared absorption peak of the sodium hyaluronate molecular group. The characteristic peak of the loaded platinum particles in this range is consistent with that of sodium hyaluronate, indicating that the platinum particles can successfully load sodium hyaluronate molecules of different molecular weights.

[0135] Figure 6 , as can be seen from the spectrum, 600cm -1 ~1700cm -1interval, and 2750cm -1 ~3300cm -1 The range is the infrared absorption characteristic peak of the palmitoyl tripeptide-5 molecular group. Platinum particles themselves do not have characteristic peaks in the above range, but after surface modification and loading of palmitoyl tripeptide-5, characteristic peaks in the above range appear, indicating that the platinum particles have successfully loaded the palmitoyl tripeptide-5 molecule.

[0136] pass Figures 2 to 6 can be This proves that the platinum particles of the present invention are successfully loaded with active ingredients.

[0137] 3. Observation of solubility changes before and after loading active substances

[0138] Solubility changes of glabridin-loaded samples: Take 0.5g of an ethanol solution of platinum particles loaded with 2:5 glabridin (Product 2 of Example 4, with a platinum concentration of 1000ppm and a glabridin concentration of 2500ppm), add 5g of pure water, and centrifuge at 3000rpm for 3 minutes. Simultaneously, take 0.5g of platinum particles not loaded with glabridin (Example 1, with a platinum concentration of 1000ppm), add 0.5g of an ethanol solution containing 0.25% glabridin, and continue to add 4.5g of pure water. Mix thoroughly, then centrifuge at 3000rpm for 3 minutes. Observe and compare the phenomena.

[0139] Changes in the solubility of the palmitoyl tripeptide-5 loaded sample: Take 0.5g of an ethanol solution of platinum particles loaded with 1:5 palmitoyl tripeptide-5 (finished product 12 of Example 7, platinum concentration of 1000ppm, palmitoyl tripeptide-5 concentration of 5000ppm), add 5g of pure water, and centrifuge at 3000rpm for 3 minutes. At the same time, take 0.5g of platinum particles not loaded with palmitoyl tripeptide-5 (Example 1, platinum concentration of 1000ppm), add 0.5g of an ethanol solution containing 0.5% palmitoyl tripeptide-5, continue to add 4.5g of pure water, mix well, and centrifuge at 3000rpm for 3 minutes. Observe and compare the phenomena.

[0140] Solubility changes of ceramide-loaded samples: 1 ml of ethanolic solution of ceramide-loaded platinum particles was mixed with 1 ml of pure water and 1 ml of squalane, heated at 70°C with stirring, and then allowed to stand. For comparison, 1 ml of the platinum particle aqueous solution from Example 1 was mixed with 1 ml of an ethanolic solution containing an equal amount of ceramide and 1 ml of squalane, heated at 70°C with stirring, and then allowed to stand. The two groups of results were observed.

[0141] Test results see 7A to 7C ;

[0142] in Figure 7AThe left sample (Pt-glab) represents glabridin-loaded platinum particles prepared according to the present invention, while the right sample (Pt-PVP, glab) represents a sample obtained by simply mixing the platinum particles from Example 1 with glabridin. Because PVP is readily soluble in water while glabridin is insoluble, the glabridin-loaded platinum particles can be centrifuged to form a black precipitate, while the simply mixed sample cannot. This demonstrates that the present invention can successfully load the active agent, thereby changing the solubility properties of the platinum particle surface, while a simple mixing method cannot successfully load the active agent.

[0143] in Figure 7B For the group loaded with palmitoyl tripeptide-5, the sample on the left (Pt-ptp5) represents the platinum particles loaded with palmitoyl tripeptide-5 prepared according to the method of the present invention, and the sample on the right (Pt-PVP, ptp5) represents the sample in which only the platinum particles of Example 1 are mixed with palmitoyl tripeptide-5. Since PVP is easily soluble in water and palmitoyl tripeptide-5 is insoluble in water, the platinum particles loaded with palmitoyl tripeptide-5 can be centrifuged to form a black precipitate, while the simply mixed sample cannot be centrifuged. This also shows that the present invention can successfully load the active substance, thereby changing the solubility properties of the platinum particle surface, while the simple mixing method cannot successfully load the active substance;

[0144] in Figure 7C The right sample (Pt-ceramide) represents ceramide-loaded platinum particles prepared according to the present invention, while the left sample (Pt-PVP, ceramide) represents the platinum particles from Example 1 simply mixed with ceramide. Because ceramide is insoluble in water but soluble in oil, the ceramide-loaded platinum particles are more lipophilic, causing the oil layer to turn black. In contrast, the unloaded platinum particles, due to their hydrophilicity, cause the water layer to turn black. This demonstrates the present invention's ability to successfully load active substances, thereby altering the solubility properties of the platinum particle surface and demonstrating its versatility.

[0145] Part 6 Application Performance Testing

[0146] 1. B16 cell melanin content test

[0147] B16 cells in good logarithmic growth phase were counted and seeded into 6-well plates, and cultured overnight in a 37°C, 5% CO2 incubator. After culturing for 16 hours in a CO2 incubator, the cells were replaced with 1% FBS-DMEM and incubated for 6 hours.

[0148] Prepare 10% FBS-DMEM medium containing the sample and add 2 ml / well to a 6-well plate. Set up solvent control wells, model wells, and experimental wells. Add the sample solvent to the solvent control wells; add MSH to the model wells; and add MSH and the test sample to the experimental wells. The final concentration of the sample is 0.5 ppm for platinum particles and 0.5 ppm for glabridin. If the sample contains only platinum particles or glabridin, use 0.5 ppm for the corresponding component.

[0149] Place the culture plates containing the above samples in a CO2 incubator for approximately 65 hours. After incubation, discard the old culture medium, wash with PBS, and digest with trypsin. Digestion is terminated by adding culture medium. A portion of the suspension is collected for total protein quantification, and the remaining portion is used for melanin content analysis. After washing with PBS, centrifuge and collect the pellet, which is then allowed to dry.

[0150] Protein quantification: Total protein in cells was quantified using a kit.

[0151] Melanin content determination: According to the results of protein quantification, a certain amount of 1M NaOH was added to the centrifuge tube to make the total protein concentration of the solution in each tube the same.

[0152] Heat the NaOH cell suspension at 80°C for 10 min to ensure that all cell clusters are dissolved and dispersed into a uniform solution. Measure the OD value at 405 nm. Repeat 3 samples for each component and calculate the average value.

[0153] Melanin inhibition rate calculation formula = (model group - sample group) / (model group - blank group) × 100% Test results can be referred to Table 5;

[0154] Table 5 Cell melanin inhibition rate test results

[0155] Example 1 Comparative Example 1-Comparative Sample 1 Comparative Example 2-Comparative Sample 2 Example 4-finished product 1 Inhibition rate 12.4 41.9 52 57.1

[0156] As can be seen from Examples 1 and 2, platinum particles alone have a slight inhibitory effect, while glabridin alone has a significant inhibitory effect on cell melanin.

[0157] Comparative Example 2 and Example 4 show that the inhibitory effect of platinum particles and glabridin effectively linked is 5.1% higher than that of the two without effective linking, indicating that the invention can significantly enhance the whitening effect of the active ingredient.

[0158] 2. Cellular inflammatory factor gene expression test

[0159] Harvest the THP-1 cell suspension from the culture flask, transfer it to a 15 mL centrifuge tube, centrifuge at 1000 rpm / min for 5 minutes, discard the supernatant, resuspend the cells in 8 mL of complete medium, and count them using a cell counter. Inoculate 5 × 105 THP-1 cells per well of a 24-well plate and add complete medium to a total volume of 0.5 mL.

[0160] Set up a blank control group, a model group, and a sample group. Add 0.5 mL of complete culture medium to the blank control group and the corresponding wells. Add 0.5 mL of sample working solution (at a concentration twice the final test concentration) to the corresponding wells of the sample group. Shake to mix thoroughly and incubate in an incubator for 18-24 hours. The final test concentration of the sample is 0.8 ppm for platinum particles and 2 ppm for madecassoside. If the sample contains only platinum particles or madecassoside, the final test concentration of the sample is 0.8 ppm for platinum particles or 2 ppm for madecassoside.

[0161] Stimulate the cells by adding 10 μL of LPS working solution (100 μg / mL) to each well of the model and sample groups, achieving a final LPS concentration of approximately 1 μg / mL. Shake to mix thoroughly, and incubate in an incubator for 24 hours. Collect cells from each well, and extract total RNA using an RNA extraction kit. Reverse transcribe the total RNA into cDNA using a reverse transcription kit. Using GAPDH as an internal reference, measure the relative expression of TNF-α and IL-1β in each group.

[0162] Inflammatory factor inhibition rate calculation formula = (model group - sample group) / (model group - blank group) × 100%

[0163] The test results can be found in Table 6;

[0164] Table 6 Cellular inflammatory factor test results

[0165]

[0166] The results of Example 2 and Comparative Example 3 show that the use of 100 nm platinum particles alone has almost no effect on activating anti-inflammatory pathways, while asiatically active glycosides can effectively activate anti-inflammatory factors.

[0167] The results of Comparative Example 4 and Example 5 show that, in terms of TNF-α, the expression of TNF-α factor increased by 4.5% and the expression of IL-1β factor increased by 4.7% when the platinum particles and asiaticoside were effectively connected compared to when the two were not effectively connected, indicating that the present invention can significantly enhance the anti-inflammatory efficacy of the active ingredients.

[0168] 3. Clinical moisturizing effect test

[0169] Ten female subjects aged 35 to 45 were selected for the experiment. Four test areas (3 cm x 3 cm) were marked on the inside of each arm, forming eight test groups. The test samples were 1% water-diluted solutions of the examples and comparative examples. The platinum and sodium hyaluronate contents of the remaining samples remained consistent with those of the samples. The dilution solvent was pure water, and the blank control group was pure water.

[0170] In a constant temperature and humidity room, the subjects sat quietly for 30 minutes, and the experimenter used the Corneometer CM825 instrument to measure the skin moisture value of each area in turn (T0 before using the sample). Then, 18mg of the corresponding sample was added to each area of ​​the subject in the order of the test area and applied evenly. After applying, the Corneometer CM825 instrument was used to measure the skin moisture value of each area in turn at the corresponding test node. A total of 4 test nodes were selected for this test (T0 before using the sample, T0 30 minutes after using the sample, T1 30 minutes after using the sample, T2 30 minutes after using the sample, T3 30 minutes after using the sample, T4 30 minutes after using the sample, T5 30 minutes after using the sample, T6 30 minutes after using the sample, T7 30 minutes after using the sample, T8 30 minutes after using the sample, T9 30 minutes after using the sample, T10 30 minutes after using the sample, T11 30 minutes after using the sample, T12 30 minutes after using the sample, T13 30 minutes after using the sample, T14 30 minutes after using the sample, T15 30 minutes after using the sample, T16 30 minutes after using the sample, T17 30 minutes after using the sample, T18 30 minutes after using the sample, T19 30 minutes after using the sample, T2 30 , 60 minutes after using the sample T 60 , 90 minutes after using the sample T 90 After the test, the data was collected and the average water content of each group of samples was calculated, and the skin moisture content improvement rate was calculated.

[0171] The formula for calculating the skin moisture content increase rate = (T 不同时间 —T0) / T0×100%

[0172] The test results can be found in Table 7;

[0173] Table 7 Human body moisturizing effect test results

[0174] Hyaluronic acid 0min 30min 60min 90 minutes 0 0.6 -0.8 0.4 Example 3 0 3.2 2.6 2.8 Comparative Example 5-Comparative Sample 5 0 21 13.4 10.9 Comparative Example 6-Comparative Sample 6 0 19.8 16.1 9.3 Example 6-Finished Product 7 0 27.9 23.4 17.2

[0175] The results of Example 3 and Comparative Example 5 show that the use of platinum particles alone has a slight effect on increasing the water content, while hyaluronic acid can effectively increase the water content of the skin;

[0176] The results of Comparative Example 6 and Example 6 show that when platinum particles and hyaluronic acid are not effectively connected, the performance is not improved compared to using hyaluronic acid alone; when the two are effectively connected, the performance is improved by 6.9%, indicating that the solution of the present invention has a good moisturizing effect when applied to hyaluronic acid.

[0177] 4. Cell collagen synthesis gene expression test

[0178] Count the NHDF cells in good logarithmic growth phase and inoculate them into 6-well plates at 2.0x10^5 cells per well. Culture them in an incubator overnight and discard the old culture medium.

[0179] Sample group: Add 2 mL of the test solution of the example or the test solution of the comparative example (prepared with complete culture medium). The final concentration of platinum in the sample test is 1 ppm, and the final concentration of palmitoyl tripeptide-5 is 1 ppm. If the sample contains only platinum particles or palmitoyl tripeptide-5, the final concentration of platinum particles or madecassoside in the sample test is 1 ppm.

[0180] Blank group and model group: add 2 mL of complete culture medium.

[0181] After adding the sample, all the above groups were cultured for 24 hours. After culture, the old culture medium was discarded, washed with PBS and then added with 2 mL of HBSS. The cells of the model group and the sample group were placed in a UV phototoxicity instrument and irradiated with UVA at a dose of 30 J / cm 2 The blank control group was shielded from ultraviolet light with aluminum foil. After irradiation, the HBSS in the wells was discarded and the cells were washed with PBS. 2 mL of the test solution from the example or the test solution from the comparative example (prepared with complete culture medium) was added to the sample group, and 2 mL of complete culture medium was added to the blank and model groups. The cells were cultured in an incubator for a further 24 h.

[0182] Total RNA from each group of cells was extracted using an RNA extraction kit, and then reverse transcribed into cDNA using a reverse transcription kit. GAPDH was used as an internal reference to detect the relative expression level of COL1A1 in each group.

[0183] Collagen synthesis enhancement rate calculation formula = (sample group - model group) / (model group) × 100%

[0184] The test results can be found in Table 8;

[0185] Table 8 Test results of cell collagen synthesis gene expression

[0186]

[0187] The results of Example 1 and Comparative Example 7 show that the use of platinum particles alone has a slight effect on the expression of cell collagen synthesis genes, while palmitoyl tripeptide-5 can effectively increase the expression of cell collagen synthesis genes.

[0188] The results of Comparative Example 8 and Example 7 show that when platinum particles and palmitoyl tripeptide-5 are not effectively connected, their performance is improved by 4.1% compared with the use of palmitoyl tripeptide-5 alone; when the two are effectively connected, their performance is further improved by 3.6% on the basis of Comparative Example 8, indicating that the invention can significantly enhance the anti-aging effect of the active ingredient.

Claims

1. A particle loaded with a cosmetic active ingredient, characterized in that: The invention relates to a platinum particle and a cosmetic active ingredient physically connected to the surface of the platinum particle, wherein the cosmetic active ingredient comprises one or more of glabridin, madecassoside, or palmitoyl tripeptide-5, and the platinum particle size is 3-200 nm. The preparation method of the particles comprises the following steps: Step 1: When the ascorbic acid and PVP aqueous solution is heated to boiling, a potassium tetrachloroplatinate solution is injected into the reaction system and the reaction is continued to obtain a reaction product; the reaction product is then precipitated and separated using acetone as a precipitant to obtain platinum particles; Step 2: Platinum particles and diethylamine are mixed and stirred to obtain diethylamine-loaded platinum particles, so that the PVP connected to the surface of the platinum particles is detached and connected to diethylamine; placing the diethylamine-loaded platinum particles in an acidic solution to release the diethylamine from the surface of the platinum particles and collecting the platinum particles from which the diethylamine has been released; Step 3: reacting the platinum particles freed from diethylamine with a solution containing a cosmetic active ingredient to obtain particles loaded with the cosmetic active ingredient.

2. The particles according to claim 1, characterized in that The weight ratio of the platinum particles to the cosmetic active ingredients is 1:0.1-20.

3. Use of the particles according to claim 1 or 2 in preparing cosmetics.

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