Supramolecular organic acid with honeycomb structure as well as preparation method and application of supramolecular organic acid

Abstract

The invention provides supramolecular organic acid with a honeycomb structure as well as a preparation method and application of the supramolecular organic acid, and particularly relates to the technical field of cosmetic intermediates. The supramolecular organic acid with the honeycomb structure comprises a supramolecular receptor, a supramolecular substrate, a first polysaccharide compound and a second polysaccharide compound, and the supramolecular receptor is organic acid. According to the supramolecular organic acid with the honeycomb structure provided by the invention, the organic acid is used as a supramolecular receptor to be combined with a supramolecular substrate to form a stable supramolecule, so that the water solubility of the organic acid is remarkably improved, and the dissolution stability of the organic acid is maintained. On the basis, the first polysaccharide compound and the second polysaccharide compound form a micro porous honeycomb structure, and supramolecules are locked and embedded in a network skeleton of the structure through hydrogen bonds, intermolecular acting force and the like. The unique honeycomb structure can realize slow and controllable release of the organic acid component in the application process, and effectively reduces the irritation of the organic acid component to the skin.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetic intermediates, and in particular to a supramolecular organic acid with a honeycomb structure, a preparation method and an application thereof. Background Art

[0002] In the cosmetics field, organic acid ingredients (such as salicylic acid, mandelic acid, azelaic acid, ferulic acid, glycyrrhetinic acid, etc.) are widely used due to their core functions such as exfoliation, anti-oxidation, and whitening. These substances exert significant effects through mechanisms such as regulating skin metabolism, inhibiting melanin production, or scavenging free radicals, and have become key active ingredients in functional skin care products. However, their actual application is subject to multiple limitations: on the one hand, organic acids generally have low water solubility, poor chemical stability (such as easy oxidative decomposition), and insufficient transdermal absorption efficiency, which makes it difficult to effectively deliver active ingredients to the targeted skin layer and limits bioavailability; on the other hand, traditional formulation technologies (such as solubilizer encapsulation or pH adjustment) can partially improve solubility, but may destroy the active structure or induce irritation reactions, making it difficult to balance efficacy and safety.

[0003] In recent years, supramolecular technology has demonstrated potential in improving solubility, stability, and transdermal performance by functionally modifying organic acids through non-covalent interactions. However, supramolecular systems lack the ability to precisely regulate the loading and release behavior of organic acids, especially in complex skin microenvironments (such as pH fluctuations and enzymatic hydrolysis), where the release rate and concentration of active ingredients are prone to uncontrollable changes. This non-steady-state release may lead to transiently high local organic acid concentrations, destroying the skin barrier function and inducing irritation reactions such as erythema and stinging, which in turn weakens the efficacy and tolerability of the product. Therefore, how to achieve precise regulation of the release behavior of organic acids to reduce irritation while maintaining the advantages of supramolecular technology has become a key technical bottleneck restricting the efficient and safe application of such ingredients.

[0004] In view of this, the present invention is proposed. Summary of the Invention

[0005] One of the objectives of the present invention is to provide a supramolecular organic acid with a honeycomb structure, aiming to solve at least one of the above-mentioned technical problems in the prior art.

[0006] A second object of the present invention is to provide a method for preparing a supramolecular organic acid having a honeycomb structure.

[0007] A third object of the present invention is to provide an application of a supramolecular organic acid having a honeycomb structure.

[0008] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are adopted:

[0009] A first aspect of the present invention provides a supramolecular organic acid having a honeycomb structure, comprising a supramolecular receptor, a supramolecular substrate, a first polysaccharide compound, and a second polysaccharide compound.

[0010] The supramolecular receptor is an organic acid; the organic acid includes at least one of salicylic acid, ferulic acid, glycyrrhetinic acid, azelaic acid and mandelic acid;

[0011] The supramolecular substrate comprises at least one of matrine, betaine, basic amino acid, cyclodextrin and calixarene.

[0012] Furthermore, the first polysaccharide compound includes at least one of biosaccharide gum-1, biosaccharide gum-4, bletilla striata polysaccharide, peach gum powder and gum arabic, preferably biosaccharide gum-1.

[0013] Preferably, the second polysaccharide compound comprises maltodextrin and / or starch, preferably maltodextrin.

[0014] Preferably, the basic amino acid includes at least one of lysine, arginine and histidine.

[0015] Furthermore, the supramolecular organic acid with a honeycomb structure comprises, by weight, 20-65 parts of a supramolecular receptor, 8-70 parts of a supramolecular substrate, 4-12 parts of a first polysaccharide compound, and 10-26 parts of a second polysaccharide compound.

[0016] Furthermore, the supramolecular organic acid having a honeycomb structure comprises, by weight, 20 to 65 parts of a supramolecular receptor, 8 to 61 parts of a supramolecular substrate, 4 to 7 parts of a first polysaccharide compound, and 10 to 22 parts of a second polysaccharide compound. A second aspect of the present invention provides a method for preparing the supramolecular organic acid having a honeycomb structure, comprising the following steps:

[0017] A. adding a supramolecular receptor and a supramolecular substrate into anhydrous ethanol, mixing them to obtain a uniform transparent liquid, and then removing the anhydrous ethanol to obtain a supramolecular crystal;

[0018] B. adding the first polysaccharide compound and the second polysaccharide compound to an ethanol aqueous solution, and performing a second mixing under vacuum conditions to obtain a honeycomb precursor solution;

[0019] C. adding the supramolecular crystal to the honeycomb precursor solution, performing a third mixing and homogenization under vacuum conditions to obtain a supramolecular organic acid solution having a honeycomb structure, and spray-drying the supramolecular organic acid solution having a honeycomb structure to obtain a supramolecular organic acid having a honeycomb structure.

[0020] Furthermore, in step A, the amount of anhydrous ethanol added is 1 to 1.5 times the total weight of the supramolecular receptor and the supramolecular substrate.

[0021] Preferably, in step A, the temperature of the first mixing is 60-80° C., and the time is 20-30 min.

[0022] Preferably, in step A, the first mixing method is stirring.

[0023] Preferably, the stirring speed is 100-300 rpm.

[0024] Furthermore, in step B, the concentration of the ethanol aqueous solution is 10 to 20 wt%.

[0025] Preferably, in step B, the amount of the ethanol aqueous solution added is 15 to 25 times the total weight of the first polysaccharide compound and the second polysaccharide compound.

[0026] Preferably, in step B, the temperature of the second mixing is 60-80°C.

[0027] Preferably, in step B, the second mixing method is stirring.

[0028] Preferably, the stirring speed is 300-500 rpm.

[0029] Furthermore, in step C, the temperature of the third mixing is 60-80°C.

[0030] Preferably, in step B, the third mixing method is stirring.

[0031] Preferably, the stirring speed is 300-500 rpm.

[0032] Furthermore, in step C, the homogenization speed is 10000-20000 rpm, and the time is 10-30 min.

[0033] Preferably, the inlet air temperature of the spray drying is 150-200° C., and the feed rate is 5-30 mL / min.

[0034] The third aspect of the present invention provides the use of the supramolecular organic acid with a honeycomb structure in the preparation of cosmetics.

[0035] Compared with the prior art, the present invention has at least the following beneficial effects:

[0036] The supramolecular organic acid with a honeycomb structure provided by the present invention forms a stable supramolecular by combining an organic acid as a supramolecular receptor with a supramolecular substrate, thereby significantly improving the water solubility of the organic acid and maintaining its dissolution stability. On this basis, the first polysaccharide compound and the second polysaccharide compound form a microporous honeycomb structure, which locks the supramolecular into its network skeleton through hydrogen bonds and intermolecular forces. This unique honeycomb structure can achieve a slow and controllable release of the organic acid component during application, effectively reducing its irritation to the skin. The supramolecular organic acid system with a honeycomb structure designed by the present invention not only solves the problems of poor solubility and insufficient stability of traditional organic acids, but also achieves gentle delivery and efficient transdermal absorption, and has multiple functions of solubilization, sustained release, transdermal and stabilization, greatly improving the utilization rate of organic acids.

[0037] The preparation method provided by the present invention achieves efficient loading and controlled release of organic acids through the step-by-step construction of supramolecules and honeycomb carriers. This preparation method is continuous and highly automated, effectively reducing batch-to-batch variability introduced by manual intervention and significantly improving product consistency and stability. Furthermore, this preparation method possesses good scalability, meeting the requirements of industrial large-scale production and providing reliable technical support for practical applications.

[0038] The application of the honeycomb-structured supramolecular organic acid provided by this invention provides a high-performance raw material solution for the downstream cosmetics industry, opening up the possibility of developing new functional cosmetics that are high-concentration, highly effective, mild, and stable. This combination of high efficiency and safety makes it particularly suitable for the development of high-value-added skin care products such as serums, facial masks, and ampoules. It is expected to promote the wider application of organic acid active ingredients in professional skin care fields such as anti-aging, acne treatment, and pigmentation improvement. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0040] Figure 1 The values for the amount of sebum on the skin surface at different time points;

[0041] Figure 2 is the change in sebum content on the skin surface in different test areas;

[0042] Figure 3 The a* value of a single pimple at different time points;

[0043] Figure 4 The a* value change of a single pimple in different test areas;

[0044] Figure 5 This is a picture showing the actual effect of improving skin acne after subject 1 used the sample of Example 1 for 0-14 days;

[0045] Figure 6 This is the actual effect of improving skin acne after subject 2 used the sample of Example 1 for 0-14 days;

[0046] Figure 7 This is the actual effect of improving skin redness after subject 3 used the sample of Example 1 for 0-14 days;

[0047] Figure 8 This is a graph showing the actual effect of improving skin redness after subject 4 used the sample of Example 1 for 0-14 days. DETAILED DESCRIPTION

[0048] In order to make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments.

[0049] Hereinafter, the terms "including", "having" and their cognates, which may be used in various embodiments of the present invention, are intended only to indicate specific features, numbers, steps, operations, elements, components or combinations of the foregoing items, and should not be understood as first excluding the existence of one or more other features, numbers, steps, operations, elements, components or combinations of the foregoing items or the possibility of adding one or more features, numbers, steps, operations, elements, components or combinations of the foregoing items.

[0050] A first aspect of the present invention provides a supramolecular organic acid having a honeycomb structure, comprising a supramolecular receptor, a supramolecular substrate, a first polysaccharide compound, and a second polysaccharide compound.

[0051] The supramolecular receptor is an organic acid; the organic acid includes at least one of salicylic acid, ferulic acid, glycyrrhetinic acid, azelaic acid and mandelic acid;

[0052] The supramolecular substrate comprises at least one of matrine, betaine, basic amino acid, cyclodextrin and calixarene.

[0053] The supramolecular organic acid with a honeycomb structure provided by the present invention forms a stable supramolecular by combining an organic acid as a supramolecular receptor with a supramolecular substrate, thereby significantly improving the water solubility of the organic acid and maintaining its dissolution stability. On this basis, the first polysaccharide compound and the second polysaccharide compound form a microporous honeycomb structure, which locks the supramolecular into its network skeleton through hydrogen bonds and intermolecular forces. This unique honeycomb structure can achieve a slow and controllable release of the organic acid component during application, effectively reducing its irritation to the skin. The supramolecular organic acid system with a honeycomb structure designed by the present invention not only solves the problems of poor solubility and insufficient stability of traditional organic acids, but also achieves gentle delivery and efficient transdermal absorption, and has multiple functions of solubilization, sustained release, transdermal and stabilization, greatly improving the utilization rate of organic acids.

[0054] The supramolecular organic acid with a honeycomb structure described in the present invention is primarily composed of a supramolecular compound and a polysaccharide compound. The supramolecular organic acid with a honeycomb structure primarily uses an organic acid as an acceptor and at least one of matrine, betaine, a basic amino acid, cyclodextrin, and calixarene as a substrate. The supramolecular organic acid with a honeycomb structure is prepared by a solvent evaporation method, then mixed with a corresponding mass of a polysaccharide compound solution and spray-dried to obtain the supramolecular organic acid with a honeycomb structure.

[0055] Furthermore, the first polysaccharide compound includes at least one of biosaccharide gum-1, biosaccharide gum-4, bletilla striata polysaccharide, peach gum powder and gum arabic, preferably biosaccharide gum-1.

[0056] Preferably, the second polysaccharide compound comprises maltodextrin and / or starch, preferably maltodextrin.

[0057] Preferably, the basic amino acid includes at least one of lysine, arginine and histidine.

[0058] The addition of the second polysaccharide compound to the formula primarily improves the product's thermal stability and powder collection rate. It also possesses antioxidant properties, prevents moisture absorption, and prevents agglomeration, playing a crucial role in the spray drying process. The first polysaccharide compound is a linear polysaccharide containing multiple sulfate groups, exhibiting the properties of a polyanionic compound. When added to an aqueous alcohol solution, it gradually expands to form a network structure. Furthermore, because the supramolecular eutectic solution is generally acidic, the supramolecular substrate can accept protons and carry a positive charge under acidic conditions, forming Coulombic forces or hydrogen bonds with the organic acid. This, to a certain extent, enhances the binding of the supramolecular eutectic to the first polysaccharide compound network through electrostatic effects. Furthermore, the first polysaccharide compound strengthens its binding to the supramolecular compound through intermolecular forces such as hydrophobic interactions and van der Waals forces. After the first polysaccharide compound's molecular network uniformly locks the supramolecular compound, spray drying and granulation are performed to produce regular microparticles, which are the supramolecular organic acid with a honeycomb structure. When it acts on the skin, the first polysaccharide compound is degraded into small molecule sugars under the action of skin enzymes, forming a breathable three-dimensional network sugar film on the skin to lock in moisture while also promoting the gradual release of internal supramolecules and entering the skin to exert its effect. The stable and slow release of organic acids enables it to reduce irritation while maintaining its efficacy.

[0059] Furthermore, the supramolecular organic acid with a honeycomb structure comprises, by weight, 20-65 parts of a supramolecular receptor, 8-70 parts of a supramolecular substrate, 4-12 parts of a first polysaccharide compound, and 10-26 parts of a second polysaccharide compound. Typically, but not limitatively, in the supramolecular organic acid having a honeycomb structure, the weight ratio of the supramolecular receptor can be, for example, 20 parts, 25 parts, 35 parts, 45 parts, 55 parts, or 65 parts, or any value within the range of 20-65 parts; the weight ratio of the supramolecular substrate can be, for example, 8 parts, 15 parts, 20 parts, 25 parts, 35 parts, 45 parts, 55 parts, or 70 parts, or any value within the range of 8-70 parts; the weight ratio of the first polysaccharide compound can be, for example, 4 parts, 6 parts, 8 parts, 10 parts, or 12 parts, or any value within the range of 4-12 parts; the weight ratio of the second polysaccharide compound can be, for example, 10 parts, 13 parts, 16 parts, 19 parts, 22 parts, 24 parts, or 26 parts, or any value within the range of 10-26 parts.

[0060] Furthermore, the supramolecular organic acid with a honeycomb structure comprises, by weight, 20 to 65 parts of a supramolecular receptor, 8 to 61 parts of a supramolecular substrate, 4 to 7 parts of a first polysaccharide compound, and 10 to 22 parts of a second polysaccharide compound. Typically, but not limitatively, in the supramolecular organic acid having a honeycomb structure, the weight ratio of the supramolecular receptor can be, for example, 20 parts, 25 parts, 35 parts, 45 parts, 55 parts, or 65 parts, or any value within the range of 20-65 parts; the weight ratio of the supramolecular substrate can be, for example, 8 parts, 15 parts, 20 parts, 25 parts, 35 parts, 45 parts, 55 parts, or 61 parts, or any value within the range of 8-61 parts; the weight ratio of the first polysaccharide compound can be, for example, 4 parts, 5 parts, 6 parts, or 7 parts, or any value within the range of 4-7 parts; the weight ratio of the second polysaccharide compound can be, for example, 10 parts, 13 parts, 16 parts, 19 parts, 20 parts, or 22 parts, or any value within the range of 10-22 parts.

[0061] The second aspect of the present invention provides a method for preparing the supramolecular organic acid having a honeycomb structure, comprising the following steps:

[0062] A. adding a supramolecular receptor and a supramolecular substrate into anhydrous ethanol, mixing them to obtain a uniform transparent liquid, and then removing the anhydrous ethanol to obtain a supramolecular crystal;

[0063] B. adding the first polysaccharide compound and the second polysaccharide compound to an ethanol aqueous solution, and performing a second mixing under vacuum conditions to obtain a honeycomb precursor solution;

[0064] C. adding the supramolecular crystal to the honeycomb precursor solution, performing a third mixing and homogenization under vacuum conditions to obtain a supramolecular organic acid solution having a honeycomb structure, and spray-drying the supramolecular organic acid solution having a honeycomb structure to obtain a supramolecular organic acid having a honeycomb structure.

[0065] The preparation method provided by the present invention achieves efficient loading and controlled release of organic acids through the step-by-step construction of supramolecules and honeycomb carriers. This preparation method is continuous and highly automated, effectively reducing batch-to-batch variability introduced by manual intervention and significantly improving product consistency and stability. Furthermore, this preparation method possesses good scalability, meeting the requirements of industrial large-scale production and providing reliable technical support for practical applications.

[0066] Furthermore, in step A, the amount of anhydrous ethanol added is 1 to 1.5 times the total weight of the supramolecular receptor and the supramolecular substrate.

[0067] Typically but not limitatively, in step A, the amount of anhydrous ethanol added can be, for example, 1 times, 1.2 times or 1.5 times the total weight of the supramolecular receptor and the supramolecular substrate, or any value within the range of 1 to 1.5 times.

[0068] Preferably, in step A, the temperature of the first mixing is 60-80° C., and the time is 20-30 min.

[0069] Typically, but not limiting, in step A, the temperature of the first mixing may be, for example, 60° C., 65° C., 70° C., 75° C., or 80° C., or any value within the range of 60 to 80° C. The time of the first mixing may be, for example, 20 min, 22 min, 25 min, 28 min, or 30 min, or any value within the range of 20 to 30 min.

[0070] Preferably, in step A, the first mixing method is stirring.

[0071] Preferably, the stirring speed is 100-300 rpm.

[0072] Typically but not limitatively, the stirring rotation speed may be, for example, 100 rpm, 150 rpm, 200 rpm or 300 rpm, or any value within the range of 100 to 300 rpm.

[0073] Furthermore, in step B, the concentration of the ethanol aqueous solution is 10 to 20 wt%.

[0074] Typically but not limitatively, in step B, the concentration of the ethanol aqueous solution can be, for example, 10 wt%, 12 wt%, 15 wt%, 18 wt% or 20 wt%, or any value within the range of 10 to 20 wt%.

[0075] Preferably, in step B, the amount of the ethanol aqueous solution added is 15 to 25 times the total weight of the first polysaccharide compound and the second polysaccharide compound.

[0076] Typically but not limitatively, in step B, the amount of the ethanol aqueous solution added can be, for example, 15 times, 18 times, 20 times, 22 times or 25 times the total weight of the first polysaccharide compound and the second polysaccharide compound, or any value within the range of 15 to 25 times.

[0077] Preferably, in step B, the temperature of the second mixing is 60-80°C.

[0078] Typically but not limitatively, in step B, the temperature of the second mixing may be, for example, 60°C, 65°C, 70°C, 75°C or 80°C, or any value within the range of 60-80°C.

[0079] Preferably, in step B, the second mixing method is stirring.

[0080] Preferably, the stirring speed is 300-500 rpm.

[0081] Typically but not limitatively, the stirring rotation speed may be, for example, 300 rpm, 350 rpm, 400 rpm, 450 rpm or 500 rpm, or any value within the range of 300 to 500 rpm.

[0082] Furthermore, in step C, the temperature of the third mixing is 60-80°C.

[0083] Typically but not limitatively, in step C, the temperature of the third mixing can be, for example, 60°C, 65°C, 70°C, 75°C or 80°C, or any value within the range of 60-80°C.

[0084] Preferably, in step B, the third mixing method is stirring.

[0085] Preferably, the stirring speed is 300-500 rpm.

[0086] Typically but not limitatively, the stirring rotation speed may be, for example, 300 rpm, 350 rpm, 400 rpm, 450 rpm or 500 rpm, or any value within the range of 300 to 500 rpm.

[0087] Furthermore, in step C, the homogenization speed is 10000-20000 rpm, and the time is 10-30 min.

[0088] Typically but not limitatively, in step C, the homogenization speed can be, for example, 10,000 rpm, 12,000 rpm, 15,000 rpm, 18,000 rpm or 20,000 rpm, or any value within the range of 10,000 to 20,000 rpm; the homogenization time can be, for example, 10 min, 15 min, 20 min, 25 min or 30 min, or any value within the range of 10 to 30 min.

[0089] Preferably, the inlet air temperature of the spray drying is 150-200° C., and the feed rate is 5-30 mL / min.

[0090] Typically, but not limiting, the inlet air temperature for the spray drying process may be, for example, 150° C., 160° C., 170° C., 180° C., 190° C., or 200° C., or any value within the range of 150 to 200° C. The feed rate for the spray drying process may be, for example, 5 mL / min, 10 mL / min, 15 mL / min, 20 mL / min, 25 mL / min, or 30 mL / min, or any value within the range of 5 to 30 mL / min.

[0091] The third aspect of the present invention provides the use of the supramolecular organic acid with a honeycomb structure in the preparation of cosmetics.

[0092] The application of the honeycomb-structured supramolecular organic acid provided by this invention provides a high-performance raw material solution for the downstream cosmetics industry, opening up the possibility of developing new functional cosmetics that are high-concentration, highly effective, mild, and stable. This combination of high efficiency and safety makes it particularly suitable for the development of high-value-added skin care products such as serums, facial masks, and ampoules. It is expected to promote the wider application of organic acid active ingredients in professional skin care fields such as anti-aging, acne treatment, and pigmentation improvement.

[0093] The present invention is further illustrated below by specific examples and comparative examples. However, it should be understood that these examples are merely for the purpose of further explanation and should not be construed as limiting the present invention in any form. The raw materials used in the examples and comparative examples of the present invention, unless otherwise specified, were prepared under conventional conditions or conditions recommended by the manufacturer. Reagents or instruments used without manufacturer's indication are all commercially available conventional products.

[0094] Examples 1-9

[0095] These embodiments provide a supramolecular salicylic acid with a honeycomb structure, and the raw materials and amounts are shown in Table 1 below.

[0096] Table 1

[0097]

[0098] The preparation method is as follows:

[0099] 1. Heat salicylic acid, matrine and anhydrous ethanol at 70°C and stir for 25 minutes at a stirring speed of 200 rpm to form a uniform transparent liquid, and then remove the anhydrous ethanol to obtain salicylic acid-matrine crystals.

[0100] 2. Heat deionized water, the second anhydrous ethanol, maltodextrin and biosaccharide gum-1 to 70°C under vacuum conditions, set the stirring speed to 400 rpm, and stir until they are evenly dissolved to obtain a transparent liquid, which is the honeycomb precursor solution.

[0101] 3. Add salicylic acid-matrine crystal powder to the honeycomb precursor solution, maintain vacuum conditions and heat to 70°C, set the stirring speed to 400 rpm, and stir until it is evenly dissolved to obtain a transparent liquid; homogenize the transparent liquid at a speed of 10,000 rpm for 20 minutes, then remove the anhydrous ethanol and spray dry it. The inlet air temperature of the spray dryer is set to 180°C and the feed rate is set to 20 mL / min.

[0102] Example 10

[0103] This embodiment provides a supramolecular salicylic acid with a honeycomb structure. The difference from Example 1 is that Bletilla striata polysaccharide is used to replace the biosaccharide gum-1 in Example 1. The remaining raw materials and preparation methods are the same as those in Example 1 and are not repeated here.

[0104] Example 11

[0105] This embodiment provides a supramolecular salicylic acid with a honeycomb structure. The difference from Example 1 is that betaine is used to replace matrine in Example 1, and gum arabic is used to replace biosaccharide gum-1 in Example 1. The remaining raw materials and preparation methods are the same as those in Example 1 and are not repeated here.

[0106] Example 12

[0107] This embodiment provides a supramolecular glycyrrhetinic acid with a honeycomb structure. The raw materials include 56g of glycyrrhetinic acid, 20g of cyclodextrin, 100g of a first anhydrous ethanol, 8g of biosaccharide gum-1, 18g of starch, 80g of a second anhydrous ethanol, and 400g of deionized water.

[0108] The preparation method of the supramolecular glycyrrhetinic acid with a honeycomb structure is the same as that of Example 1, with the raw materials and amounts being replaced accordingly.

[0109] Example 13

[0110] This embodiment provides a supramolecular mandelic acid with a honeycomb structure. The raw materials include 56g of mandelic acid, 20g of lysine, 100g of a first anhydrous ethanol, 8g of biosaccharide gum-1, 18g of maltodextrin, 80g of a second anhydrous ethanol, and 400g of deionized water.

[0111] The preparation method of the supramolecular mandelic acid with a honeycomb structure is the same as that of Example 1, with the raw materials and amounts being replaced accordingly.

[0112] Example 14

[0113] This embodiment provides a supramolecular azelaic acid with a honeycomb structure, the raw materials including 56g of azelaic acid, 20g of calixarene, 100g of a first anhydrous ethanol, 8g of biosaccharide gum-1, 18g of maltodextrin, 80g of a second anhydrous ethanol, and 400g of deionized water.

[0114] The preparation method of the supramolecular azelaic acid with a honeycomb structure is the same as that of Example 1, with the raw materials and amounts being replaced accordingly.

[0115] Example 15

[0116] This embodiment provides a supramolecular ferulic acid with a honeycomb structure. The raw materials include 56g of ferulic acid, 20g of betaine, 100g of a first anhydrous ethanol, 8g of biosaccharide gum-1, 18g of maltodextrin, 80g of a second anhydrous ethanol, and 400g of deionized water.

[0117] The preparation method of the supramolecular ferulic acid with a honeycomb structure is the same as that of Example 1, with the raw materials and amounts being replaced accordingly.

[0118] Comparative Example 1

[0119] This comparative example provides a supramolecular salicylic acid, which is composed of 23g of salicylic acid and 77g of matrine. Salicylic acid and matrine are heated at 80°C until melted, and then cooled to room temperature to obtain supramolecular salicylic acid.

[0120] Comparative Example 2

[0121] This comparative example provides a salicylic acid having a honeycomb structure, and the preparation method is as follows:

[0122] 1. Heat 10.6 g of salicylic acid, 48.8 g of Poloxamer 407, 16.6 g of Tween 80, and 400 g of deionized water at 70°C with stirring to form a homogeneous transparent liquid to obtain phase A.

[0123] 2. Add 17g of maltodextrin and 7g of Biosaccharide Gum-1 to phase A to form a homogeneous solution. Finally, dry the solution using a spray dryer with an inlet air temperature of 165°C and a feed rate of 12.5mL / min. The resulting powder is salicylic acid with a honeycomb structure.

[0124] Comparative Example 3

[0125] This comparative example provides encapsulated salicylic acid, prepared as follows: 10g of salicylic acid and 90g of hydroxypropyl β-cyclodextrin were stirred at 85°C for 1 hour to form a homogeneous, transparent solution; 500g of deionized water was slowly added to the solution, stirring continuously until a homogeneous solution was formed. The resulting homogeneous solution was dried using a spray dryer with an inlet air temperature of 165°C and a feed rate of 12.5mL / min. The resulting powder was the encapsulated salicylic acid.

[0126] Comparative Example 4

[0127] This comparative example provides a supramolecular glycyrrhetinic acid, which differs from comparative example 1 in that glycyrrhetinic acid is used instead of salicylic acid. The remaining raw materials and preparation methods are the same as those in comparative example 1 and will not be repeated here.

[0128] Comparative Example 5

[0129] This comparative example provides a glycyrrhetinic acid with a honeycomb structure. The difference from comparative example 2 is that glycyrrhetinic acid is used instead of salicylic acid. The remaining raw materials and preparation methods are the same as those in comparative example 2 and will not be repeated here.

[0130] Comparative Example 6

[0131] This comparative example provides a packaged glycyrrhetinic acid, which differs from comparative example 3 in that glycyrrhetinic acid is used instead of salicylic acid. The remaining raw materials and preparation methods are the same as those in comparative example 3 and will not be repeated here.

[0132] Comparative Example 7

[0133] This comparative example provides a supramolecular mandelic acid, which differs from comparative example 1 in that mandelic acid is used instead of salicylic acid. The remaining raw materials and preparation methods are the same as those in comparative example 1 and are not described again here.

[0134] Comparative Example 8

[0135] This comparative example provides a mandelic acid with a honeycomb structure. The difference from comparative example 2 is that mandelic acid is used instead of salicylic acid. The remaining raw materials and preparation methods are the same as those in comparative example 2 and are not repeated here.

[0136] Comparative Example 9

[0137] This comparative example provides an encapsulated mandelic acid, which differs from comparative example 3 in that mandelic acid is used instead of salicylic acid. The remaining raw materials and preparation methods are the same as those in comparative example 3 and are not described again here.

[0138] Test Example 1

[0139] The products obtained in all examples, as well as comparative examples 2-3, 5-6, and 8-9 are all in powder form; the products obtained in comparative examples 1, 4, and 7 are liquid.

[0140] The products of the examples and comparative examples were placed in deionized water to prepare dispersions with mass concentrations of 5%, 10%, and 15%, respectively. The water solubility, dispersion stability, and stickiness of the dispersions after application to the skin were evaluated. The results are recorded in Table 2.

[0141] Table 2

[0142]

[0143]

[0144] Test Example 2

[0145] The products obtained in the examples and comparative examples were tested for organic acid release rate.

[0146] First, the products obtained in the embodiment and the comparative example were respectively prepared into a sample solution with a mass concentration of 1%. The molecular weight was 15000 dialysis tubing was cut into 2.5cm*2.5cm sizes. The cut dialysis tubing inner layer was fixed upwards to the vertical diffusion cell opening. A gasket the size of the diffusion cell opening was fixed above the dialysis tubing and fixed between the diffusion chamber and the receiving chamber. The diffusion chamber and the outer ring of the receiving chamber were fixed with sealing film to prevent leakage. The receiving solution was PBS. 0.3mL of the sample to be tested was added to the supply cell and the receiving chamber was sealed with sealing film. The assembled vertical diffusion cell was placed in an in vitro osmometer and the experimental conditions were set as follows: temperature 32°C, stirring speed 600rpm, 0.3mL was taken from the receiving chamber branch at 0.5h, 1h, 2h, 4h, 6h and 22h, and the organic acid concentration was determined by HPLC after filtering with a 0.22μm PTFE membrane. The release amount of the organic acid was calculated.

[0147] The obtained data are recorded in Table 3.

[0148] Table 3

[0149]

[0150]

[0151] Test Example 3

[0152] The products obtained in the examples and comparative examples were subjected to a retention test.

[0153] Test method for retention: Permeability verification was conducted according to the in vitro scalp test guidelines stipulated by the OECD / OCDE European Guidelines for the Testing of Chemicals in Skin Tissue. First, 2% organic acid sample solution was prepared in sequence according to the examples and comparative examples. Then, the Bama pigskin was washed and cut into 2.2 cm 2The skin was hydrated in normal saline for 30 minutes, removed, and dried. TEWL values were measured, and skin with a TEWL less than 15 was selected. The skin was fixed between the diffusion chamber and the receiving chamber of a vertical diffusion cell using PBS as the receiving solution. 33 μL of the sample to be tested was added to the supply chamber. The assembled vertical diffusion cell was placed in an in vitro permeameter, and the experimental conditions were set as follows: temperature 37°C, stirring speed 600 rpm, and permeation time 20 hours. After permeation, the pig skin was removed from the diffusion cell, rinsed 10 times with ethanol, washed three times, then rinsed 10 times with water, washed once, and then blotted dry. The skin was taped 15 times, the tape was cut into pieces, and placed in a 10 mL sample vial. 5 mL of 80% ethanol was added as the extractant. The supernatant was sonicated for 30 minutes, filtered through a 0.22 μm PTFE filter, and the stratum corneum organic acid content was determined by HPLC. This represents the organic acid content retained in the stratum corneum. The data are recorded in Table 4.

[0154] Table 4

[0155]

[0156]

[0157] Test Example 4

[0158] With reference to the group standard "T / HPCIA006-2022 Determination of mild irritation of cosmetics - zebrafish embryo method", an experiment was designed to compare the embodiments and comparative examples to explore their mild and non-irritating efficacy.

[0159] The specific operations are as follows:

[0160] 1. Control group: ① Blank control group: standard dilution water; ② Positive control group: 0.95 mg / mL SDS solution.

[0161] 2. Product dosage grouping: The examples and comparative examples were sequentially prepared into sample solutions with an organic acid content of 0.5%.

[0162] 3. Experimental process:

[0163] 3.1. Confirmation of Maximum Tolerable Concentration

[0164] Based on the conditions of the formal trial, several concentration groups were set at widely spaced intervals. Each group was treated with 10 normal 24 hpf (24 hours post-fertilization) wild-type AB zebrafish embryos (24-well cell culture plates, 1.0 mL of sample solution). The fish were observed and recorded for 24 hours. Within 24 hours, the number of zebrafish deaths in each experimental group was counted and promptly removed. Preliminary studies determined the concentration that resulted in the highest survival of all fish without toxicity. The concentration for the formal trial was set within this safe range.

[0165] 3.2 Formal Test

[0166] Normally developed 24 hpf wild-type AB zebrafish embryos were randomly selected and placed in a 24-well cell culture plate, 10 per well. A blank control group, a positive control group, and a test sample group were set up respectively. 1 mL of standard dilution water was added to each group (before sample addition). After counting the stress response frequency of the zebrafish embryos, 1 mL of the corresponding sample solution was added (after sample addition) (standard dilution water was added to the blank control group, 0.95 mg / mL SDS solution was added to the positive control group, and the test sample solution was added to the test sample group). The stress response frequency of the zebrafish embryos within 2 minutes was counted, and each experiment was repeated twice.

[0167] 3.3. Judgment basis

[0168] Table 5 Irritation Evaluation Standards

[0169]

[0170] Table 6 Effects of the samples of Examples and Comparative Examples on the stress response frequency of zebrafish embryos

[0171]

[0172]

[0173] Note: The content of organic acid in each sample at the experimental concentration is 0.5%.

[0174] Comparative analysis of Examples 1-5 shows that when the content of biosaccharide gum-1 is consistent and the content of salicylic acid is low, the release sample is stable, the release is slow, the skin keratin retention is low, and the skin feel is suitable; when the content of salicylic acid increases, the stability is easily changed, the skin keratin retention and retention rate are slightly reduced compared to Example 1, while still maintaining a sustained release; the sample of Example 1 has better stability, skin feel, high skin keratin retention, retention rate and balanced release rate, and can be released slowly; Examples 1, 2 and 5 do not cause irritation to the skin, while Examples 3 and 4 have a slight irritation. Examples 1-5 show that when the ratio of supramolecules and the content of biosaccharide gum-1 are appropriate, the skin retention rate is high, and reducing or increasing the salicylic acid content will lead to a decrease in the retention rate. Comparative analysis of Example 1 and Examples 6-9 shows that when the active ingredients remain consistent, a decrease in the content of biosaccharide gum-1 will lead to poor sample stability, accelerated salicylic acid release, increased irritation, and decreased skin keratin retention and retention rate. This is because when the content of biosaccharide gum-1, which forms a honeycomb three-dimensional structure, decreases, its structural stability decreases; when the content of biosaccharide gum-1 increases, the honeycomb three-dimensional structure becomes stronger, the stability increases, but its release slows down and is incomplete, and the skin feel deteriorates, and the irritation does not change significantly compared to Example 1. Compared with Example 1 and Example 10, the skeleton of the honeycomb three-dimensional structure is replaced by biosaccharide gum-1 with bletilla striata polysaccharide, and the skin retention and release effect are both reduced, the irritation does not change significantly, and the release effect is poor. Comparative analysis of Example 1 and Comparative Examples 1-3 shows that the simple supramolecular compound does not have good stability and skin permeability, and will cause irritation by sudden release; the stability of the single honeycomb three-dimensional salicylic acid is poor, easy to release suddenly and easy to irritate, indicating that supramolecular technology has an excellent effect in stabilizing salicylic acid and enhancing transdermal penetration, and the simple biosaccharide gum-1 cannot help salicylic acid significantly improve stability and sustained release effect; Comparative Example 3 shows that the embedding rate of hydroxypropyl beta-cyclodextrin for salicylic acid is low, and the stability and sustained release effect are poor; the skin retention rate of supramolecular honeycomb salicylic acid (Example 1-10) is significantly higher than that of supramolecular salicylic acid (Comparative Example 1), salicylic acid with honeycomb structure (Comparative Example 2), and encapsulated salicylic acid (Comparative Example 3). In the honeycomb structure, matrine is replaced by betaine and biosaccharide gum is gum arabic to obtain Example 11, and its sustained release effect and irritation are basically unchanged, and the retention amount is reduced (compared to Example 1), which may be the difference caused by the supramolecular compatibility. The honeycomb-structured glycyrrhetinic acid (Example 12) showed significantly higher skin retention than supramolecular glycyrrhetinic acid (Comparative Example 4), conventional honeycomb-structured glycyrrhetinic acid (Comparative Example 5), and encapsulated glycyrrhetinic acid (Comparative Example 6), while also significantly reducing irritation. Similarly, replacing the organic acid in the honeycomb structure with mandelic acid (Example 13) showed improved retention, sustained release, and reduced irritation compared to supramolecular mandelic acid (Comparative Example 7), conventional honeycomb mandelic acid (Comparative Example 8), and encapsulated mandelic acid (Comparative Example 9).

[0175] In summary, the sample group of Example 1 has good stability and skin feel, good sustained release effect and excellent skin keratin retention capacity of up to 43.76 μg / cm 2 , the retention rate is 26.05%, and it can significantly reduce irritation.

[0176] Test Example 5

[0177] By comparing the improvement of the amount of sebum on the skin surface by the sample of Example 1 and free salicylic acid, the oil control effect of the two products was explored. This method, based on the principle of photometry, uses a special matte tape 0.1mm thick. After absorbing oil from human skin, it becomes translucent, and its light transmittance changes accordingly. The more oil absorbed, the greater the light transmittance, thus measuring the oil content of the skin. This method is an indirect measurement of sebaceous gland secretions; the larger the value, the more sebum there is on the skin surface.

[0178] The obtained data is plotted Figure 1 and Figure 2 , Figure 1 The measured value of sebum content on the skin surface at different time points, in μg / cm 2 , sample size N = 32. Compared with before use, the difference is statistically significant, "*" indicates 0.01≤p<0.05, "**" indicates p<0.01, and "ns" indicates p≥0.05.

[0179] Figure 2 The change in sebum content on the skin surface of different test areas, in μg / cm 2 The differences were statistically significant compared with the free salicylic acid area, "*" indicates 0.01 ≤ p < 0.05, "**" indicates p < 0.01, and "ns" indicates p ≥ 0.05.

[0180] from Figure 1 and Figure 2 As can be seen, after 14 days of using the product in Example 1, the amount of sebum on the skin's surface decreased by 23.10%, a significant decrease (p ≤ 0.05). Compared to free salicylic acid, the change in sebum on the skin's surface in the area treated with the product in Example 1 was significantly greater than that in the control sample (p ≤ 0.05). This demonstrates that the product in Example 1 has significant oil-control capabilities, significantly reducing oil secretion on the skin's surface.

[0181] Test Example 6

[0182] Salicylic acid has acne-removing properties. The improvement in acne after application of the sample in Example 1 and free salicylic acid to the skin surface was compared to assess their acne-removing abilities. Skin condition is typically analyzed by measuring VISLA parameters: VISIA utilizes standard light, ultraviolet light, polarized light, and RBX technology to assess skin condition. IPP software image analysis utilizes image grayscale values for analysis and evaluation. The a* value of a single pimple is used to represent acne condition; a smaller a* value indicates a greater reduction in facial redness.

[0183] The obtained data is plotted Figure 3 and Figure 4 . Figure 3 A* values of individual acne at different time points (unit: au), sample size N = 32. Statistically significant differences compared to pre-treatment. "*" indicates 0.01 ≤ p < 0.05, "**" indicates p < 0.01, and "ns" indicates p ≥ 0.05.

[0184] Figure 4 Figure 2 shows the change in a* value for a single pimple at different test areas (unit: au). Sample size: N = 32. Statistically significant differences were observed compared with the free salicylic acid area. "*" indicates 0.01 ≤ p < 0.05, "**" indicates p < 0.01, and "ns" indicates p ≥ 0.05.

[0185] from Figure 3 and Figure 4 As can be seen, compared to pre-use, after 7 and 14 days of use, the a* value of a single pimple decreased by 7.67% and 11.68%, respectively, demonstrating significant decreases (p < 0.05). Compared to free salicylic acid, the change in a* value of a single pimple in the test sample area after 14 days of use was significantly greater than that in the control sample area (p < 0.05). This data demonstrates that Example 1 has significantly superior acne-removing capabilities to free salicylic acid.

[0186] Figure 5 This is a picture showing the actual effect of improving skin acne after subject 1 used the sample of Example 1 for 0-14 days; Figure 6 This is the actual effect of improving skin acne after subject 2 used the sample of Example 1 for 0-14 days; Figure 7 This is the actual effect of improving skin redness after subject 3 used the sample of Example 1 for 0-14 days; Figure 8 This is a graph showing the actual effect of improving skin redness after subject 4 used the sample of Example 1 for 0-14 days.

[0187] Finally, it should be noted that the above-described embodiments are only specific implementations of the present invention, which are used to illustrate the technical solutions of the present invention, rather than to limit them. The scope of protection of the present invention is not limited thereto. Although the present invention has been described in detail with reference to the above-described embodiments, those skilled in the art should understand that any person skilled in the art can modify or easily conceive of changes to the technical solutions described in the above-described embodiments within the technical scope disclosed by the present invention, or replace some of the technical features therein with equivalents. Such modifications, changes, or replacements do not deviate from the spirit and scope of the technical solutions of the embodiments of the present invention, and should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A supramolecular organic acid having a honeycomb structure, characterized in that: comprising a supramolecular receptor, a supramolecular substrate, a first polysaccharide compound, and a second polysaccharide compound; The supramolecular receptor is an organic acid; The organic acid comprises at least one of salicylic acid, ferulic acid, glycyrrhetinic acid, azelaic acid and mandelic acid; The supramolecular substrate comprises at least one of matrine, betaine, basic amino acid, cyclodextrin and calixarene.

2. The supramolecular organic acid having a honeycomb structure according to claim 1, characterized in that The first polysaccharide compound comprises at least one of biosaccharide gum-1, biosaccharide gum-4, bletilla striata polysaccharide, peach gum powder and gum arabic, preferably biosaccharide gum-1; Preferably, the second polysaccharide compound comprises maltodextrin and / or starch, preferably maltodextrin; Preferably, the basic amino acid includes at least one of lysine, arginine and histidine.

3. The supramolecular organic acid having a honeycomb structure according to claim 1 or 2, characterized in that According to weight parts, it comprises 20-65 parts of supramolecular receptor, 8-70 parts of supramolecular substrate, 4-12 parts of first polysaccharide compound and 10-26 parts of second polysaccharide compound.

4. The supramolecular organic acid having a honeycomb structure according to claim 3, characterized in that According to parts by weight, the composition comprises 20 to 65 parts of supramolecular receptor, 8 to 61 parts of supramolecular substrate, 4 to 7 parts of first polysaccharide compound and 10 to 22 parts of second polysaccharide compound.

5. A method for preparing a supramolecular organic acid having a honeycomb structure according to any one of claims 1 to 4, characterized in that: The following steps are involved: A. adding a supramolecular receptor and a supramolecular substrate into anhydrous ethanol, mixing them to obtain a uniform transparent liquid, and then removing the anhydrous ethanol to obtain a supramolecular crystal; B. adding the first polysaccharide compound and the second polysaccharide compound to an ethanol aqueous solution, and performing a second mixing under vacuum conditions to obtain a honeycomb precursor solution; C. adding the supramolecular crystal to the honeycomb precursor solution, performing a third mixing and homogenization under vacuum conditions to obtain a supramolecular organic acid solution having a honeycomb structure, and spray-drying the supramolecular organic acid solution having a honeycomb structure to obtain a supramolecular organic acid having a honeycomb structure.

6. The preparation method according to claim 5, characterized in that In step A, the amount of anhydrous ethanol added is 1 to 1.5 times the total weight of the supramolecular receptor and the supramolecular substrate; Preferably, in step A, the temperature of the first mixing is 60-80° C. and the time is 20-30 min; Preferably, in step A, the first mixing method is stirring; Preferably, the stirring speed is 100-300 rpm.

7. The preparation method according to claim 5, characterized in that In step B, the concentration of the ethanol aqueous solution is 10-20 wt%; Preferably, in step B, the amount of the ethanol aqueous solution added is 15 to 25 times the total weight of the first polysaccharide compound and the second polysaccharide compound; Preferably, in step B, the temperature of the second mixing is 60-80°C; Preferably, in step B, the second mixing method is stirring; Preferably, the stirring speed is 300-500 rpm.

8. The preparation method according to claim 5, characterized in that In step C, the temperature of the third mixing is 60-80°C; Preferably, in step B, the third mixing method is stirring; Preferably, the stirring speed is 300-500 rpm.

9. The preparation method according to any one of claims 5 to 8, characterized in that: In step C, the homogenization speed is 10000-20000 rpm, and the time is 10-30 min; Preferably, the inlet air temperature of the spray drying is 150-200° C., and the feed rate is 5-30 mL / min.

10. Use of the supramolecular organic acid with a honeycomb structure according to any one of claims 1 to 4 in the preparation of cosmetics.

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