Penetration enhancing composition based on sodium lauroyl lactylate

Abstract

The application discloses a sodium lauroyl lactylate-based penetration composition containing ergothioneine and sodium lauroyl lactylate, wherein the weight ratio of the ergothioneine and the sodium lauroyl lactylate is 20:1-1:20, and the content of the sodium lauroyl lactylate is 0.01wt%-1wt%. The penetration rate of the composition is greater than or equal to 50% after 24h vertical transdermal diffusion. The application further discloses application of the penetration composition in skin external agents.

Description

Technical Field

[0001] This invention relates to the field of topical skin preparations, specifically to the targeted permeation-enhancing effect of sodium lauroyl lactylate on a specific amount of ergothioneine, and particularly to a permeation-enhancing composition based on sodium lauroyl lactylate, which can enhance the permeation and absorption of ergothioneine in the skin and has excellent stability. Background Technology

[0002] The skin is the largest organ in the human body, accounting for approximately 16% of body weight. Besides its functions of protection, sensation, and temperature regulation, the skin also participates in the body's absorption, metabolism, and immune response. The pharmaceutical industry offers various transdermal absorption formulations to help drugs penetrate the skin and enter the body to achieve therapeutic effects.

[0003] Aside from the pharmaceutical industry, the field most relevant to skin is topical skincare products, such as cosmetics. People apply various effective cosmetics to their skin to help it achieve a healthy and comfortable state, such as moisturizing, preventing dryness, brightening, reducing wrinkles, soothing, and treating acne. These cosmetics act directly on our skin. Ideally, effective cosmetics should allow their active ingredients to penetrate the epidermis or dermis to exert their corresponding effects. However, the main problem with transdermal penetration is the obstruction of the stratum corneum. Therefore, we use various methods to enhance skin permeability, allowing the effective ingredients of cosmetics to be absorbed by the skin and exert their true effects.

[0004] Commonly used penetration enhancement technologies include chemical penetration enhancement, nanotechnology, physical penetration enhancement, and biological penetration enhancement. Details are as follows:

[0005] 1. Chemical Penetration Enhancement Technology: This technique works by interacting with lipids in the stratum corneum, altering their arrangement and thus enhancing skin permeability. Common chemical penetration enhancers include surfactants, propylene glycol, and azone. Its advantages include low cost, direct addition to skincare product formulations, and the absence of additional equipment.

[0006] 2. Nanotechnology: Nanotechnology is now widely used in cosmetics, such as liposomes, lipid vesicles, nanoemulsions, and solid lipid nanoparticles. Its advantages include: 1) improving the stability of cosmetic ingredients such as unsaturated fatty acids, vitamins, or antioxidants in the formulation; 2) enhancing the permeability of certain ingredients, such as vitamins or antioxidants; 3) improving the efficacy and tolerability of UV absorbers; and 4) making products more aesthetically pleasing, for example, making the active mineral particles in mineral sunscreens smaller, thus preventing noticeable white patches on the face.

[0007] 3. Physical Permeation Enhancement Techniques: These techniques use physical methods to alter the structure of the stratum corneum, thereby expanding the transdermal pathway. Common methods include iontophoresis, ultrasound-guided iontophoresis, and microneedling, all of which require additional auxiliary equipment. Iontophoresis uses external electrodes to apply a microcurrent for several minutes to several hours, driving molecules through the stratum corneum via electrophoresis. Therefore, the introduced substance must be water-soluble and charged. Ultrasound-guided iontophoresis, also known as ultrasound therapy, uses ultrasound waves greater than 20kHz to penetrate active ingredients into the skin. Microneedling involves creating "tiny pores" in the superficial or surface layers of the skin through needle punctures, allowing larger or more active ingredients to penetrate.

[0008] 4. Bio-penetration enhancement technology: This technology can directly increase the permeability of lipids in the stratum corneum, or indirectly affect skin permeability by altering lipid metabolism. It includes substances such as penetration-enhancing peptides, hyaluronic acid, ceramides, and their analogues. Bio-penetration enhancers have low toxicity, high biocompatibility, and good application potential.

[0009] Prior art, such as Chinese patent application CN111228209A, discloses a cosmetic composition, its preparation method, its application, and a cosmetic essence. The cosmetic composition comprises the following components by mass fraction: 1%–30% Bacillus fermentation product, 1%–30% ergothioneine / pine mushroom extract, 1%–10% ceramide complex, 1%–20% saccharide isomers, and 10%–96% stabilizer, with the sum of the mass fractions of all components being 100%. The ceramide complex includes ceramide 3, ceramide 1, ceramide 6II, salicylphytosphoprotein, cholesterol, sodium lauroyl lactylate, carbomer, xanthan gum, and water. Although this application mentions the simultaneous addition of ergothioneine and sodium lauroyl lactylate, these are simply added without revealing a targeted penetration-enhancing effect of sodium lauroyl lactylate on ergothioneine.

[0010] Similarly, Chinese patent application CN114146009B discloses a DHA anti-aging and anti-inflammatory nanocomposition, its preparation method, and its application. The nanocomposition consists of the following components in the indicated mass percentages: DHA 8%, ergothioneine 15%, borscht 8%, vitamin E 8%, soybean lecithin 4%, dipalmitoylphosphatidylcholine 4%, cholesterol 2%, 1,3-propanediol 10%, butylene glycol 10%, sodium lauroyl lactylate 8%, and 23% water. This is also a simple addition, and it does not reveal that sodium lauroyl lactylate has a targeted permeation-enhancing effect on ergothioneine.

[0011] Chinese patent application CN116496429A discloses a hydroxyethyl deacetylated chitosan, its preparation method, a self-assembled transdermal delivery system for enhancing absorption, and its applications. This hydroxyethyl deacetylated chitosan has an average molecular weight of 7460 Da and, as a penetration enhancer for active ingredients such as peptides, proteins, PCA, Zn, and ergothioneine, exhibits a significant improvement in absorption. While this application mentions hydroxyethyl deacetylated chitosan as a penetration enhancer for ergothioneine, it does not disclose specific penetration efficiency.

[0012] We unexpectedly discovered that sodium lauroyl lactylate, when combined with ergothioneine, can enhance the skin penetration of ergothioneine. Furthermore, sodium lauroyl lactylate can be directly added to cosmetic formulations as an emulsifier or surfactant, making it widely applicable, inexpensive, and readily available. Summary of the Invention

[0013] The present invention aims to provide a penetration-enhancing composition based on sodium lauroyl lactylate, which can improve the penetration and absorption of ergothioneine in the skin, and the system is stable.

[0014] The present invention provides a penetration-enhancing composition based on sodium lauroyl lactyl lactate, which comprises ergothioneine and sodium lauroyl lactyl lactate, wherein the weight ratio of ergothioneine to sodium lauroyl lactate is 20:1 to 1:20, and wherein the content of sodium lauroyl lactyl lactate is 0.01wt% to 1wt%.

[0015] In a preferred embodiment, the content of sodium lauroyl lactylate is 0.01wt%-0.7wt%.

[0016] In a preferred embodiment, the weight ratio of ergothioneine to sodium lauroyl lactylate is 2:1 to 1:10.

[0017] In a preferred embodiment, the weight ratio of ergothioneine to sodium lauroyl lactylate is 1:1 to 1:10.

[0018] In a preferred embodiment, the composition may further comprise ≥98 wt% of a carrier suitable for topical skin applications.

[0019] Preferably, the carrier is selected from water.

[0020] In a preferred embodiment, the permeability of the composition after 24 hours of vertical transdermal diffusion is ≥50%.

[0021] Preferably, the permeability of the composition after 24 hours of vertical transdermal diffusion is 50.15-79.48%.

[0022] The present invention also provides the use of sodium lauroyl lactyl lactate to promote the penetration of ergothioneine.

[0023] In a preferred embodiment, the weight ratio of ergothioneine to sodium lauroyl lactylate is 20:1 to 1:20;

[0024] Preferably, the weight ratio is 2:1 to 1:10;

[0025] The preferred ratio is 1:1 to 1:10 by weight.

[0026] The present invention also provides the use of penetration-enhancing compositions based on sodium lauroyl lactyl lactate in topical skin preparations.

[0027] In a preferred embodiment, the composition is used in a topical skin preparation at an amount of 0.01 wt% to 20 wt%.

[0028] In a preferred embodiment, the topical skin agent is selected from: creams, lotions, serums, gels, lotions, masks, cleansers, shower gels, makeup removers, shampoos and conditioners, oils, colognes, etc.

[0029] The beneficial effects of this invention are:

[0030] The sodium lauroyl lactyl lactate combination obtained according to the above scheme can ensure high stability and increase the transdermal absorption of ergothioneine in the skin. Attached Figure Description

[0031] Figure 1 This is a schematic diagram of the vertical diffusion cell used in the permeability test example.

[0032] Figure 2 The high performance liquid chromatogram of ergothionein in Example 3 (3h);

[0033] Figure 3 The high performance liquid chromatogram (24h) of ergothionein in Example 3 is shown. Detailed Implementation

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. While any methods and materials similar or equivalent to those described herein may be used to practice or test the invention, preferred methods and materials are described herein. For the purposes of this invention, the following terms are defined.

[0035] To provide a more concise description, some of the quantitative expressions given herein are not modified by the term "approximately". It should be understood that, whether or not the term "approximately" is explicitly used, each quantity given herein is intended to refer to an actual given value, and also to an approximation of such given values ​​that can be reasonably inferred by one of ordinary skill in the art, including approximations of such given values ​​caused by experimental and / or measurement conditions.

[0036] To provide a more concise description, some quantities in this document are described as a range from approximately X to approximately Y. It should be understood that when describing a range, the range is not limited to the upper and lower limits stated, but should include the entire range from approximately X to approximately Y, or any quantities in between.

[0037] Carriers suitable for use in topical skin preparations

[0038] The carrier applicable to the field of topical skin agents described in this invention is water, and the topical skin agents can be selected from: creams, lotions, serums, gels, lotions, masks, cleansers, shower gels, makeup removers, shampoos and conditioners, oils, and colognes.

[0039] Penetration

[0040] The permeability described in this invention is calculated based on the amount of ergothioneine that permeates through pigskin after a 24-hour vertical transdermal diffusion experiment. In this invention, a permeability ≥50% after a 24-hour vertical transdermal diffusion experiment is considered to have a permeation-enhancing effect.

[0041] The following describes the technical solution of the present invention in detail through preferred embodiments. However, the scope of the present invention is not limited to these embodiments, which are intended to illustrate the technical solution of the present invention and not to limit the scope of the present invention. Test methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, all percentages and parts are by weight.

[0042] The experimental materials used in the embodiments of the present invention are as follows:

[0043] (a) Experimental materials

[0044] 1. Sodium lauroyl lactylate (trade name PATIONIC 138C, purchased from RITA Corporation)

[0045] 2. Ergothioneine (purchased from Shanghai Ergothioneine Biotechnology Group Co., Ltd.)

[0046] 3. Deionized water (homemade)

[0047] 4. Neosolue™-Aqulio bis-diethoxydiethylene glycol cyclohexane 1,4-dicarboxylic acid ester (purchased from Nippon Seika Co., Ltd.)

[0048] 5,1,2-Pentanediol (trade name: effisin™ pg multifunctional, purchased from Ashland LLC)

[0049] 6. Lauryl azone (purchased from TGI)

[0050] 7. RH40 (brand name Cremophor® RH 40, purchased from BASF)

[0051] 8,1,2-Hexanediol (trade name KMO-6, purchased from OSAKA ORGANIC CHEMICAL INDUSTRY LTD.)

[0052] 9. Propylene glycol (trade name: Propylene Glycol USP / EP, purchased from Dow Chemical)

[0053] 10. 0.9wt% physiological saline (homemade)

[0054] (II) Experimental Instruments

[0055] 1. Fixed mixer IKA RW20

[0056] 2. Weighing balance METTLER TOLEDO PL602-S

[0057] 3. Transdermal Diffusion Tester TK-12D, Shanghai Yuyan Scientific Instruments Co., Ltd.

[0058] 4. Skin on the back of miniature pigs aged 1-2 months (Chongqing Meisheng Trading Co., Ltd.)

[0059] 5. High-performance liquid chromatography instrument, equipped with a diode array detector, Waters ARC HPLC

[0060] 6. MMM Friocell 707 Incubator

[0061] 7. Analytical balance METTLER TOLEDO XS205

[0062] 8. CNC Ultrasonic Cleaner KQ-800DE, Kunshan Ultrasonic Instrument Co., Ltd.

[0063] Examples 1-14: Preparation of aqueous solutions of ergothioneine and sodium lauroyl lactylate at different concentrations

[0064] Sample preparation: Weigh ergothioneine and sodium lauroyl lactylate according to the mass fractions shown in Table 1, add deionized water to make up to 100 parts by mass, and stir at room temperature until a transparent liquid is formed.

[0065] Table 1. Components in aqueous solutions of ergothioneine and sodium lauroyl lactylate at different concentrations

[0066]

[0067] Test Example 1: Permeability Test

[0068] Test samples: aqueous solutions of ergothioneine and sodium lauroyl lactylate at different concentrations prepared in Examples 1-14

[0069] Test steps:

[0070] 1) Remove the frozen pig skin, thaw it, and then use scissors to remove the subcutaneous fat and connective tissue.

[0071] 2) Soak the pigskin in physiological saline for 1 hour.

[0072] 3) Turn on the water bath of the transdermal diffusion instrument to heat (constant temperature 32℃).

[0073] 4) Place a magnetic stir bar in the receiving pool, then fix the cut pigskin between the supply and receiving pools, with the epidermis facing upwards and the dermis in contact with the receiving pool. Add physiological saline into the receiving pool through the sampling tube as the receiving solution, and remove any air bubbles. Cover the supply pool with a coverslip, place it in a transdermal diffusion apparatus, and equilibrate for 1 hour at a constant temperature (32℃) with stirring (440 r / min).

[0074] 5) Add each sample of the embodiment into the supply pool, i.e., where the raw material is located, to contact the pigskin, and stir at a constant temperature (32°C) (440 r / min). After 3 h and 24 h, take the receiving liquid from the sampling tube for testing.

[0075] The ergothioneine content in the receiving liquid was determined using high-performance liquid chromatography (HPLC), and the cumulative permeability was calculated. Details are as follows:

[0076] 6) The ergothioneine content in the receiving liquid was determined using high performance liquid chromatography.

[0077] a. Chromatographic conditions: The chromatographic column was an Agilent HILIC Plus column (4.6 mm * 100 mm, 3.5 μm), the mobile phase was 0.1% formic acid acetonitrile solution - 0.1% formic acid aqueous solution (80:20 v / v), the flow rate was 1 mL / min, the column temperature was 30 ℃, the injection volume was 10 μL, and the detection wavelength was 262 nm.

[0078] b. Preparation of ergothioneine standard stock solution (0.5 g / L): Weigh 50 mg of ergothioneine standard (accurate to 0.01 mg), dissolve in water and dilute to 100 mL. Store at 4°C.

[0079] c. Preparation of ergothioneine standard working solutions: Accurately transfer a certain amount of ergothioneine standard stock solution and dilute it stepwise with 0.1% formic acid methanol solution to obtain a series of standard working solutions (mass concentrations of 5 μg / mL, 10 μg / L, 25 μg / mL, 50 μg / mL, and 100 μg / mL, respectively).

[0080] d. Standard curve plotting: Determine the standard working solution under the chromatographic conditions described above, and plot the standard curve with the mass concentration of the standard working solution as the abscissa and the peak area as the ordinate.

[0081] e. Sample preparation and determination: Weigh 0.1–0.5 g (accurate to 0.1 mg) of sample into a 10 mL stoppered colorimetric tube, add 8 mL of 0.1% formic acid-methanol solution, and sonicate for 20 min. Make up to volume with 0.1% formic acid-methanol solution, shake well, and filter a portion of the liquid through a 0.22 μm filter membrane. Then, determine the sample under the chromatographic conditions described above. Quantify the sample using the standard curve. The analyte response value in the sample solution should be within the linear range of the standard curve.

[0082] 7) Calculate the cumulative permeability

[0083] EGT penetration rate = (m 取样量 ×C EGT ) / (m 上样量 ×C EGT总 ) ×100%

[0084] Table 2. Osmotic Tests of Alkaloid and Sodium Lauroyl Lactoyl Lactate Aqueous Solutions at Different Concentration Ratios

[0085]

[0086] Compared with examples containing ergothioneine, water, and sodium lauroyl lactylate, examples containing the same concentration of ergothioneine and water are considered to have a synergistic permeation-enhancing effect if the former has a higher permeability value than the latter; otherwise, no synergistic permeation-enhancing effect is considered to be present.

[0087] The permeability of the composition sample prepared in Example 2 was 4.01% after 3 hours, which was less than the 4.12% permeability of the composition sample prepared in Example 1 after 3 hours. Furthermore, the permeability of the composition sample prepared in Example 2 was 36.92% after 24 hours, which was less than the 46.13% permeability of the composition sample prepared in Example 1 after 24 hours. Therefore, it was concluded that the composition sample prepared in Example 2 had no permeation effect.

[0088] like Figure 2 The composition sample prepared in Example 3 showed a permeability of 21.15% after 3 hours, which was greater than the 4.12% permeability of the composition sample prepared in Example 1 after 3 hours. Figure 3 The composition sample prepared in Example 3 showed a permeability of 69.57% after 24 hours, which was greater than the permeability of 46.13% of the composition sample prepared in Example 1 after 24 hours. Therefore, it is believed that the composition sample prepared in Example 3 has a synergistic permeation effect.

[0089] The permeability of the composition sample prepared in Example 4 was 25.56% after 3 hours, which was greater than the 4.12% permeability of the composition sample prepared in Example 1 after 3 hours. Furthermore, the permeability of the composition sample prepared in Example 4 was 79.48% after 24 hours, which was greater than the 46.13% permeability of the composition sample prepared in Example 1 after 24 hours. Therefore, it is believed that the composition sample prepared in Example 4 has a synergistic permeation effect.

[0090] In summary, by comparing the 3-hour and 24-hour permeability rates, it can be seen that when the ergothioneine content in the composition is 1 wt% and the sodium lauroyl lactylate content is 0.5-1 wt% (i.e., ergothioneine:sodium lauroyl lactylate = 2:1 or 1:1), the composition exhibits a synergistic permeation-enhancing effect. However, when the sodium lauroyl lactylate content is 0.05 wt% (i.e., ergothioneine:sodium lauroyl lactylate = 20:1), the composition has no permeation-enhancing effect.

[0091] The permeability of the composition sample prepared in Example 6 was 14.62% after 3 hours, which was greater than the 10.46% permeability of the composition sample prepared in Example 5 after 3 hours. Furthermore, the permeability of the composition sample prepared in Example 6 was 48.11% after 24 hours, which was greater than the 47.01% permeability of the composition sample prepared in Example 5 after 24 hours. Therefore, it is believed that the composition sample prepared in Example 6 has a synergistic permeation effect.

[0092] The composition sample prepared in Example 7 had a permeability of 20.25% after 3 hours, which was greater than the 10.46% permeability of the composition sample prepared in Example 5 after 3 hours. Furthermore, the composition sample prepared in Example 7 had a permeability of 50.15% after 24 hours, which was greater than the 47.01% permeability of the composition sample prepared in Example 5 after 24 hours. Therefore, it is believed that the composition sample prepared in Example 7 has a synergistic permeability effect.

[0093] The composition sample prepared in Example 8 had a permeability of 24.57% after 3 hours, which was greater than the 10.46% permeability of the composition sample prepared in Example 5 after 3 hours. Furthermore, the composition sample prepared in Example 8 had a permeability of 59.25% after 24 hours, which was greater than the 47.01% permeability of the composition sample prepared in Example 5 after 24 hours. Therefore, it is believed that the composition sample prepared in Example 8 has a synergistic permeability effect.

[0094] The composition sample prepared in Example 9 had a permeability of 30.95% after 3 hours, which was greater than the permeability of the composition sample prepared in Example 5 after 3 hours (10.46%). Furthermore, the composition sample prepared in Example 9 had a permeability of 70.31% after 24 hours, which was greater than the permeability of the composition sample prepared in Example 5 after 24 hours (47.01%). Therefore, it is believed that the composition sample prepared in Example 9 has a synergistic permeation effect.

[0095] In summary, by comparing the 3-hour and 24-hour permeability, it can be seen that when the ergothioneine content in the composition is 0.1 wt% and the sodium lauroyl lactylate content is 0.1-0.7 wt% (i.e., ergothioneine: sodium lauroyl lactylate = 1:1-7), the composition exhibits a synergistic permeation-enhancing effect.

[0096] The composition sample prepared in Example 11 had a permeability of 37.79% after 3 hours, which was greater than the 10.64% permeability of the composition sample prepared in Example 10 after 3 hours. Furthermore, the composition sample prepared in Example 11 had a permeability of 77.61% after 24 hours, which was greater than the 45.36% permeability of the composition sample prepared in Example 10 after 24 hours. Therefore, it is believed that the composition sample prepared in Example 11 has a synergistic permeation effect.

[0097] The permeability of the composition sample prepared in Example 12 was 5.79% after 3 hours, which was less than the 10.64% permeability of the composition sample prepared in Example 10 after 3 hours. Furthermore, the permeability of the composition sample prepared in Example 12 was 25.59% after 24 hours, which was less than the 45.36% permeability of the composition sample prepared in Example 10 after 24 hours. Therefore, it was concluded that the composition sample prepared in Example 12 did not have a synergistic permeation effect.

[0098] In summary, by comparing the 3-hour and 24-hour permeability rates, it can be seen that when the ergothioneine content in the composition is 0.01 wt% and the sodium lauroyl lactylate content is 0.1 wt% (i.e., ergothioneine:sodium lauroyl lactylate = 1:10), the composition exhibits a synergistic permeation-enhancing effect. However, when the sodium lauroyl lactylate content is 0.2 wt% (i.e., ergothioneine:sodium lauroyl lactylate = 1:20), the composition has no permeation-enhancing effect.

[0099] The composition sample prepared in Example 14 had a permeability of 28.25% after 3 hours, which was greater than the 11.41% permeability of the composition sample prepared in Example 13 after 3 hours. Furthermore, the composition sample prepared in Example 14 had a permeability of 72.74% after 24 hours, which was greater than the 59.70% permeability of the composition sample prepared in Example 13 after 24 hours. Therefore, it is believed that the composition sample prepared in Example 14 has a synergistic permeability effect.

[0100] In summary, by comparing the 3-hour and 24-hour permeability, it can be seen that when the ergothioneine content in the composition is 0.001 wt% and the sodium lauroyl lactylate content is 0.01 wt% (i.e., ergothioneine: sodium lauroyl lactylate = 1:10), the composition exhibits a synergistic permeation-enhancing effect.

[0101] Test Example 2: Stability Test

[0102] Test samples: aqueous solutions of ergothioneine and sodium lauroyl lactylate at different concentrations prepared in Examples 1-14

[0103] Stability evaluation method: The sample was placed in a constant temperature chamber at room temperature (25℃) and a constant temperature chamber at high temperature (48℃) for 1 week and 4 weeks respectively. After the sample was returned to room temperature at each time point, the sample was observed to see if there were any color changes, precipitation of crystals or particles, or changes in odor.

[0104] If the color remains unchanged, use ○ to represent it;

[0105] If the color turns yellow or undergoes other changes, indicate it with an ×.

[0106] Odor index: No change in odor (acceptable) scores 0;

[0107] A slightly unpleasant odor (acceptable) scores 1-2.

[0108] A sulfurous smell (unacceptable) scores 3-4.

[0109] A noticeably stronger sulfur smell appears, and the odor is unpleasant (unacceptable), scoring 5 points.

[0110] Table 3. Stability tests of aqueous solutions of ergothioneine and sodium lauroyl lactylate at different concentrations.

[0111]

[0112] After a one-week stability test, the compositions prepared in Examples 1-14 showed no change in color, and no crystals or particles precipitated. The odor remained unchanged at room temperature. However, the compositions prepared in Examples 1-4 exhibited a slightly unpleasant odor at high temperatures. The compositions prepared in Examples 5-14 showed no change in odor at high temperatures.

[0113] In summary, after one week of stability testing, when the composition contained 1 wt% ergothioneine, a slightly unpleasant odor was observed at high temperatures, but not at room temperature. However, when the composition contained 0.1%, 0.01 wt%, or 0.001 wt% ergothioneine, no odor change was observed at either room temperature or high temperatures.

[0114] After a 4-week stability test, the composition samples prepared in Examples 1-14 showed no change in odor at room temperature. However, the composition samples prepared in Examples 1-9 exhibited a slightly unpleasant odor at high temperatures. The composition samples prepared in Examples 10-14 showed no change in odor at high temperatures.

[0115] Therefore, after a 4-week stability test, when the ergothioneine content in the composition was 1 wt% or 0.1 wt%, there was a slightly unpleasant odor compared to the results of a 1-week stability test at high temperature. However, when the ergothioneine content in the composition was 0.01 wt% or 0.001 wt%, there was no change in odor compared to the results of a 1-week stability test at both room temperature and high temperature.

[0116] Comparative Examples 1-5: Preparation of aqueous solutions of ergothioneine with different penetration enhancers

[0117] Sample preparation: Weigh ergothioneine and different penetration enhancers according to the mass fractions shown in Table 4, add deionized water to make up to 100 mass fractions, and stir at room temperature until a transparent liquid is formed.

[0118] Table 4. Content of each component in aqueous solutions of ergothioneine and different penetration enhancers

[0119]

[0120] Note: The weight ratio of lauryl azone to RH40 in the table is 3:7.

[0121] Test Example 3: Permeability Test

[0122] Test samples: Aqueous solutions of ergothioneine prepared in Comparative Examples 1-5 with different penetration enhancers

[0123] Test steps:

[0124] 1) Remove the frozen pig skin, thaw it, and then use scissors to remove the subcutaneous fat and connective tissue.

[0125] 2) Soak the pigskin in physiological saline for 1 hour.

[0126] 3) Turn on the water bath of the transdermal diffusion instrument to heat (constant temperature 32℃).

[0127] 4) Place a magnetic stir bar in the receiving pool, then fix the cut pigskin between the supply and receiving pools, with the epidermis facing upwards and the dermis in contact with the receiving pool. Add physiological saline into the receiving pool through the sampling tube as the receiving solution, and remove any air bubbles. Cover the supply pool with a coverslip, place it in a transdermal diffusion apparatus, and equilibrate for 1 hour at a constant temperature (32℃) with stirring (440 r / min).

[0128] 5) Add each sample of the embodiment into the supply pool, i.e., where the raw material is located, to contact the pigskin, and stir at a constant temperature (32°C) (440 r / min). After 3 h and 24 h, take the receiving liquid from the sampling tube for testing.

[0129] The ergothioneine content in the receiving liquid was determined using high-performance liquid chromatography (HPLC), and the cumulative permeability was calculated. Details are as follows:

[0130] 6) The ergothionein content in the receiving liquid was determined using high performance liquid chromatography.

[0131] a. Chromatographic conditions: The chromatographic column was an Agilent HILIC Plus column (4.6 mm * 100 mm, 3.5 μm), the mobile phase was 0.1% formic acid acetonitrile solution - 0.1% formic acid aqueous solution (80:20 v / v), the flow rate was 1 mL / min, the column temperature was 30 ℃, the injection volume was 10 μL, and the detection wavelength was 262 nm.

[0132] b. Preparation of ergothioneine standard stock solution (0.5 g / L): Weigh 50 mg of ergothioneine standard (accurate to 0.01 mg), dissolve in water and dilute to 100 mL. Store at 4°C.

[0133] c. Preparation of ergothioneine standard working solutions: Accurately transfer a certain amount of ergothioneine standard stock solution and dilute it stepwise with 0.1% formic acid methanol solution to obtain a series of standard working solutions (mass concentrations of 5 μg / mL, 10 μg / L, 25 μg / mL, 50 μg / mL, and 100 μg / mL, respectively).

[0134] d. Standard curve plotting: Determine the standard working solution under the chromatographic conditions described above, and plot the standard curve with the mass concentration of the standard working solution as the abscissa and the peak area as the ordinate.

[0135] e. Sample preparation and determination: Weigh 0.1–0.5 g (accurate to 0.1 mg) of sample into a 10 mL stoppered colorimetric tube, add 8 mL of 0.1% formic acid-methanol solution, and sonicate for 20 min. Make up to volume with 0.1% formic acid-methanol solution, shake well, and filter a portion of the liquid through a 0.22 μm filter membrane. Then, determine the sample under the chromatographic conditions described above. Quantify the sample using the standard curve. The analyte response value in the sample solution should be within the linear range of the standard curve.

[0136] 7) Calculate the cumulative permeability

[0137] EGT penetration rate = (m 取样量 ×C EGT ) / (m 上样量 ×C EGT总 ) ×100%

[0138] Table 5. Osmotic Tests of Alkaloid and Sodium Lauroyl Lactoyl Lactate Aqueous Solutions at Different Concentration Ratios

[0139]

[0140] In this application, a permeability enhancement effect is considered to be achieved when the permeability of the tested composition sample is greater than 50% after 24 hours.

[0141] Human skin's epidermis is composed of a large lipid bilayer, so we generally choose raw materials with both lipophilic and hydrophilic structures, or polyols, as penetration enhancers to help active ingredients penetrate the skin. Commonly used Neosolue™-Aqulio and RH40 are such lipophilic and hydrophilic raw materials; lauryl azone, as one of the most commonly used penetration enhancers in the pharmaceutical field, helps drugs absorb transdermally; in addition, polyols, such as 1,2-pentanediol, have good skin affinity and are also used as penetration enhancers to help active ingredients penetrate. The penetration enhancers used in Comparative Examples 1-5 are all typical and commonly used chemical penetration enhancers, whose advantages are low cost and the ability to be directly added to skincare product formulations without the need for additional equipment.

[0142] Therefore, the permeability of the composition samples prepared in Comparative Examples 1-2 and 5 was greater than 50% after 24 hours, indicating that the composition samples prepared in Comparative Examples 1-2 and 5 had a synergistic permeation-promoting effect.

[0143] The composition samples prepared in Comparative Examples 3 and 4 had no permeation-enhancing effect; combined with the permeability data of the composition samples prepared in Example 11 in Table 2, it can be seen that the aqueous solution of ergothioneine and polyglycerol-10 laurate had the highest permeability, reaching 77.61%, and the highest permeation-enhancing efficiency.

[0144] Test Example 4: Stability Test

[0145] Test samples: Aqueous solutions of ergothioneine prepared in Comparative Examples 1-5 with different penetration enhancers

[0146] Stability evaluation method: The sample was placed in a constant temperature chamber at room temperature (25℃) and a constant temperature chamber at high temperature (48℃) for 1 week and 4 weeks respectively. After the sample was returned to room temperature at each time point, the sample was observed to see if there were any color changes, precipitation of crystals or particles, or changes in odor.

[0147] If the color remains unchanged, use ○ to represent it;

[0148] If the color turns yellow or undergoes other changes, indicate it with an ×.

[0149] Table 6. Stability tests of ergothioneine aqueous solutions with different penetration enhancers

[0150]

[0151] After one week of stability testing, comparative examples 1-5 showed no change in color and no crystals or particles were precipitated.

[0152] After 4 weeks of stability testing, comparative examples 1-5 showed no change in color and no crystals or particles were precipitated.

[0153] Application examples

[0154] The compositions of sodium lauroyl lactylate and ergothioneine from Examples 1-14 were used in the preparation of topical skin agents. These topical skin agents are preferably cosmetic compositions, such as toners, serums, creams, masks, gels, cleansers, shampoos, bath products, and makeup removers. The sodium lauroyl lactylate compositions from Examples 1-14 constitute 0.01% to 20% (w / w) of the topical skin agent by weight. A preferred weight percentage is 0.01% to 10% (w / w). A more preferred weight percentage is 0.01% to 5% (w / w).

[0155] The following are specific examples of the application of sodium lauroyl lactylate compositions (Examples 1-14) in topical skin preparations, along with the formulations and preparation methods of these dosage forms. In the tables below, "-" indicates no additives.

[0156] Application Example 1: Preparation of Face Cream

[0157]

[0158] Application Example 2: Emulsion Preparation

[0159]

[0160] Application Example 3: Preparation of Gel

[0161]

[0162] Application Example 4: Preparation of Toner

[0163]

[0164] Application Example 5: Preparation of Serum

[0165]

[0166] Application Example 6: Preparation of Facial Masks

[0167]

[0168] Application Example 7: Preparation of Eye Cream

[0169]

[0170] Application Example 8: Preparation of Spray

[0171]

[0172] Application Example 9: Preparation of Shower Gel

[0173]

[0174] Application Example 10: Preparation of Facial Cleanser

[0175]

[0176] Application Example 11: Preparation of Essence Water

[0177]

[0178] In all the above examples of specific applications of topical skin agents, the sodium lauroyl lactylate compositions of Examples 1-14 can be used directly in the formulation, either partially or completely, to replace deionized water, or can be used directly as a formulation.

Claims

1. A penetration-enhancing composition based on sodium lauroyl lactylate, comprising ergothioneine, sodium lauroyl lactylate, and water, wherein the weight ratio of ergothioneine to sodium lauroyl lactylate is 2:1 to 1:10, wherein... The content of sodium lauroyl lactylate is 0.01wt%-1wt%, and the content of ergothioneine is 0.001wt%-1wt%.

2. The composition according to claim 1, characterized in that, The content of sodium lauroyl lactylate is 0.01wt%-0.7wt%.

3. The composition according to claim 2, characterized in that, The weight ratio of ergothioneine to sodium lauroyl lactylate is 1:1 to 1:

10.

4. The composition according to any one of claims 1-3, characterized in that, The composition has a permeability of ≥50% after 24 hours of vertical transdermal diffusion.

5. The composition according to claim 4, characterized in that, The permeability of the composition after 24 hours of vertical transdermal diffusion is 50.15-79.48%.

6. Use of sodium lauroyl lactylate to promote the permeation of ergothioneine, wherein the weight ratio of ergothioneine to sodium lauroyl lactylate is 2:1-1:10, wherein, The content of sodium lauroyl lactylate is 0.01wt%-1wt%, and the content of ergothioneine is 0.001wt%-1wt%.

7. The use as described in claim 6, characterized in that, The weight ratio of ergothioneine to sodium lauroyl lactylate is 1:1 to 1:

10.

8. The use of the composition of claim 5 in a non-therapeutic topical skin preparation.

9. The application as described in claim 8, wherein the composition is used in a topical skin preparation at an amount of 0.01 wt% to 20 wt%.

10. The application as described in claim 8, wherein, The topical skin agents are selected from: creams, lotions, gels, lotions, masks, cleansers, shower gels, makeup removers, shampoos and conditioners, oils, and colognes.

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