Method for improving stability of sialic acid-p-hydroxyacetophenone solution

Abstract

The invention relates to the technical field of cosmetics, in particular to a method for improving the stability of a sialic acid-p-hydroxyacetophenone solution. The method comprises the following steps: mixing p-hydroxyacetophenone with a stabilizer, and then mixing with sialic acid to obtain sialic acid-p-hydroxyacetophenone mixed liquor; the stabilizer is sulfite and / or hydrosulfite, and the addition amount of the stabilizer is 0.005%-0.2% by mass. Aiming at the problems of discoloration of sialic acid-p-hydroxyacetophenone solution and loss of sialic acid, the invention provides a method, all the raw materials are mixed according to a specific sequence on the basis of a specific stabilizer through a specific processing technology, the stability of the obtained solution is remarkably improved, the solution does not discolorate after being placed for a long time, the loss rate of sialic acid is low, and the method is suitable for industrial production. The method has important application value in the field of production of cosmetics containing sialic acid at the same time.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and in particular to a method for improving the stability of sialic acid-p-hydroxyacetophenone solution. Background Technology

[0002] Sialic acid (SA), also known as sialic acid, is a naturally occurring carbohydrate widely found in organisms and has attracted much attention due to its unique biological activities. In cosmetics, functional foods, and pharmaceuticals, sialic acid is often used as a core active ingredient, playing a vital role in promoting cell health, moisturizing, anti-aging, and improving skin texture. Because liquid products containing sialic acid, especially water-based formulas, are susceptible to microbial contamination and spoilage, preservatives are usually added during product manufacturing to ensure product stability, safety, and shelf life.

[0003] Among numerous preservatives, p-hydroxyacetophenone (p-Hydroxyacetophenone) stands out as an ideal choice due to its multiple advantages. Firstly, p-Hydroxyacetophenone has a natural source, aligning with the current market preference for mild and environmentally friendly ingredients. Secondly, in addition to its basic preservative capabilities, it also possesses excellent antioxidant and soothing properties. However, a challenging issue arises during actual research and development. When sialic acid (SA) is mixed with p-Hydroxyacetophenone in an aqueous solution, the system exhibits a noticeable discoloration over time, typically manifesting as a gradual yellowing or darkening of the solution. This indicates that p-Hydroxyacetophenone or SA has reacted or degraded, resulting in a decrease in its effective concentration.

[0004] To address the stability issue of sialic acid, existing technologies disclose several methods. For example, the applicant has disclosed the use of sulfites or bisulfites as stabilizers in some solution systems to prevent degradation; or adjusting the pH of the solution to reduce its degradation rate. However, while these methods are effective for aqueous solutions of sialic acid, they are largely ineffective for complex systems of sialic acid and p-hydroxyacetophenone, and the problems of discoloration and decreased sialic acid content persist. Summary of the Invention

[0005] To address the problems existing in the prior art, the present invention provides a method for improving the stability of sialic acid-p-hydroxyacetophenone solution.

[0006] In a first aspect, the present invention provides a method for improving the stability of a sialic acid-p-hydroxyacetophenone solution, comprising: mixing p-hydroxyacetophenone with a stabilizer, and then mixing it with sialic acid to obtain a sialic acid-p-hydroxyacetophenone mixture; wherein the stabilizer is a sulfite and / or a bisulfite, and the amount added is 0.005% to 0.2% by mass percentage.

[0007] Because p-hydroxyacetophenone has low solubility, it is usually dissolved by heating in conventional processes before being compounded with other components. However, due to the known instability of its aqueous solution, sialic acid is avoided in cosmetic and other applications due to the need for heat treatment. Therefore, when preparing a sialic acid-p-hydroxyacetophenone compound solution, p-hydroxyacetophenone is dissolved first before adding sialic acid. The sialic acid can be a direct powder raw material or a pre-prepared high-concentration mother liquor.

[0008] In previous studies, this invention discovered that sialic acid, when directly mixed with p-hydroxyacetophenone, exhibited severe discoloration, especially at high sialic acid concentrations, leading to degradation and discoloration even after short-term storage. Subsequent experiments attempted to mitigate this by using stabilizers (sulfites or bisulfites). However, the results showed that adding stabilizers last or mixing sialic acid and sulfites beforehand, as per conventional methods, failed to resolve the degradation and discoloration issues. Furthermore, adjusting the pH to neutral also failed to improve the discoloration. Through extensive research, this invention accidentally discovered that adjusting the mixing order could solve the problem. Therefore, a method was proposed to mix the raw materials in a specific order under specific temperature conditions. This method produces a sialic acid-p-hydroxyacetophenone solution that does not discolor even after prolonged storage, with extremely low sialic acid loss. Simultaneously, the preservative effect remains unaffected. Although the prior art CN111937874B proposes that mixing sodium metabisulfite with p-hydroxyacetophenone can yield a p-hydroxyacetophenone solution that is stable and does not change color in an alcohol solution, sialic acid is not an alcohol solution, and sialic acid itself is also prone to discoloration. Moreover, the key point of this invention is not just finding a stabilizer, but finding a process method for adding the stabilizer and the two components.

[0009] The method further includes adjusting the pH of the sialic acid-p-hydroxyacetophenone mixture to 3.5-7.5. That is, the sialic acid-p-hydroxyacetophenone mixture of the present invention can adapt to both neutral and acidic environments and remain stable, thus having a wide range of applications. pH adjustment methods include, but are not limited to, triethanolamine, arginine, sodium hydroxide, potassium hydroxide, and calcium hydroxide. Since sialic acid is a moderately strong acid, arginine is easier to use when adjusting the pH.

[0010] Furthermore, the sialic acid content is 0.01% to 5% by mass.

[0011] Furthermore, the mass percentage of p-hydroxyacetophenone is 0.01% to 1%.

[0012] This invention is applicable to improvement methods for sialic acid with a mass percentage of 0.01% to 0.5% and p-hydroxyacetophenone with a mass percentage of 0.01% to 1%, and can fully cover the specific situations in which sialic acid and p-hydroxyacetophenone are added to cosmetics.

[0013] Furthermore, the stabilizer has a mass percentage content of 0.01% to 0.1%.

[0014] Furthermore, the sulfite includes one or more of sodium sulfite, potassium sulfite, ammonium sulfite, sodium metabisulfite, or potassium metabisulfite.

[0015] Furthermore, the bisulfite includes one or more of sodium bisulfite, potassium bisulfite, or ammonium bisulfite.

[0016] Secondly, the present invention provides the application of the aforementioned method in the preparation of cosmetics containing sialic acid and p-hydroxyacetophenone.

[0017] Thirdly, the present invention provides the application of the aforementioned method in improving the discoloration or loss of sialic acid in sialic acid-p-hydroxyacetophenone solutions.

[0018] Fourthly, the present invention provides a sialic acid-p-hydroxyacetophenone aqueous solution composition, which is prepared by the aforementioned method.

[0019] The present invention has the following beneficial effects: This invention addresses the discoloration and sialic acid loss issues of sialic acid-p-hydroxyacetophenone (SAP) solutions by providing a method based on a specific stabilizer and a specific processing technique. The method involves mixing the raw materials in a specific order, resulting in a solution with significantly improved stability that remains unchanged even after prolonged storage, and with extremely low SAP loss. The method is applicable to SAP solutions of varying concentrations, particularly high-concentration SAP solutions. This method significantly improves discoloration and SAP loss without affecting the preservative effect, ultimately enhancing stability during processing and storage. This is of great significance in the production of cosmetics containing both SAP and P-hydroxyacetophenone. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1This refers to the results of Examples 4 and 7 provided in Experiment 1 of the present invention after being placed at room temperature, light conditions, and 45°C for 12 weeks.

[0022] Figure 2 This is the result of comparative examples 1-6 provided in Experimental Example 2 of the present invention after being placed at room temperature for 4 weeks.

[0023] Figure 3 This is the result of comparative examples 1-6 provided in Experimental Example 2 of the present invention after being placed at 45°C for 4 weeks.

[0024] Figure 4 This is the result of comparative examples 1-6 provided in Experimental Example 2 of the present invention after being placed under natural light for 4 weeks.

[0025] Figure 5 This is the result of comparative examples 1-6 provided in Experimental Example 2 of the present invention after being placed at room temperature for 12 weeks.

[0026] Figure 6 This is the result of comparative examples 1-6 provided in Experimental Example 2 of the present invention after being placed at 45°C for 12 weeks.

[0027] Figure 7 This refers to the results of comparative examples 1-6 provided in Experimental Example 2 of this invention after being placed under natural light conditions for 12 weeks.

[0028] Figure 8 This refers to the results of comparative examples 7-8 provided in Experimental Example 2 of this invention after being placed at room temperature, light conditions, and 45°C for 12 weeks. Detailed Implementation

[0029] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0030] Unless otherwise specified, the experimental methods involved in the following embodiments are conventional methods in the art. For example, you can refer to the experimental manual in the art or follow the conditions recommended in the manufacturer's instructions.

[0031] Unless otherwise specified, all experimental materials and reagents used in the following examples are commercially available.

[0032] Unless otherwise specified, all concentrations mentioned in the following examples are mass percentages (w / w).

[0033] In the following examples, the sialic acid content was determined by high-performance liquid chromatography (HPLC). Specific test conditions were as follows: Shimadzu Lc-15c; Bio-Rad AMINEX HPX 87 Horganic Analysis Column (300 × 7.8 mm); column temperature 60℃; mobile phase 6 mmol sulfuric acid, flow rate 0.6 ml / min; detection wavelength 210 nm. All experiments were repeated three times, and the results are the average of the three trials.

[0034] Example In this embodiment, the method for preparing the sialic acid-p-hydroxyacetophenone solution includes the following steps: Weigh a certain amount of p-hydroxyacetophenone and prepare an aqueous solution of p-hydroxyacetophenone. Heat to 60°C to dissolve and cool to room temperature. Add a stabilizer (sodium bisulfite, sodium metabisulfite, or sodium sulfite) and sialic acid in sequence, and then adjust the pH with arginine.

[0035] This invention utilizes different sialic acid contents, different stabilizers, and adjusts the pH at different levels, as detailed in the table below: Table 1. Dosage of each component in each embodiment.

[0036] Comparative Example In Comparative Examples 1-6, the method for preparing the sialic acid-p-hydroxyacetophenone solution includes the following steps: Weigh a certain amount of p-hydroxyacetophenone and prepare an aqueous solution of p-hydroxyacetophenone. Heat to 60°C to dissolve and cool to room temperature. Add sialic acid, arginine, and a stabilizer (sodium metabisulfite).

[0037] The components of each comparative example are as follows: Table 2. Dosage of each component in Comparative Examples 1-6

[0038] In Comparative Examples 7-8, the method for preparing the sialic acid-p-hydroxyacetophenone solution includes the following steps: Weigh a certain amount of p-hydroxyacetophenone and prepare an aqueous solution. Heat to 60°C to dissolve and cool to room temperature. Dissolve sialic acid and a stabilizer (sodium metabisulfite) to prepare a solution for later use. Add the solution containing sialic acid and the stabilizer to the p-hydroxyacetophenone, and then adjust the pH with arginine.

[0039] The components of each comparative example are as follows: Table 3. Dosage of each component in each comparative example

[0040] Experimental Example 1 After preparing the solutions of the aforementioned embodiments, the present invention processes them under the following conditions: (1) Under room temperature conditions, the room was left to stand for 12 weeks under normal indoor light.

[0041] (2) Let it stand for 12 weeks under natural light at room temperature.

[0042] (3) Let it stand in a constant temperature chamber at 45℃ for 12 weeks.

[0043] After processing, observe the color change of the samples in each example, detect the loss rate of sialic acid (calculated by detecting the sialic acid content before and after processing), and observe whether bacteria grow.

[0044] The results are shown in the table below: Table 4 Color changes and sialic acid loss rates for each embodiment

[0045] like Figure 1 As shown, from left to right, the first sample is the control, and the second to fourth samples are the images of Example 4 (left image) and Example 7 (right image) after being processed by (1) to (3).

[0046] Experimental Example 2 After preparing the solutions of Comparative Examples 1-6, the present invention treats them under the following conditions: (1) Under room temperature conditions, it was placed indoors for 12 weeks without being exposed to natural light.

[0047] (2) Let it stand for 12 weeks under natural light at room temperature.

[0048] (3) Let it stand in a constant temperature chamber at 45℃ for 12 weeks.

[0049] The results are as follows Figure 2 - Figure 8 As shown in the figure: i) By week 4, the proportions in the room temperature treatment group showed varying degrees of discoloration, while the discoloration was more severe in the 45°C treatment group and the room temperature + natural light treatment group.

[0050] ii) By week 12, all groups showed obvious discoloration, with the natural light group showing the most obvious discoloration, followed by the 45℃ group.

[0051] Therefore, it can be concluded that the sialic acid-p-hydroxyacetophenone solutions obtained by the processes in Comparative Examples 1-8 have poor stability, and obvious discoloration was observed in all of them during the stability test, which does not meet the experimental requirements.

[0052] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for improving the stability of a solution of cystosidic acid-p-hydroxyacetophenone, characterized in that, The method comprises: mixing p-hydroxyacetophenone with a stabilizer, and then mixing the stabilizer with the bird's nest acid to obtain a bird's nest acid-p-hydroxyacetophenone mixture; the stabilizer is a sulfite and / or bisulfite, and the addition amount is 0.005%-0.2% in terms of mass percentage.

2. The method of claim 1, wherein, The method further comprises adjusting the pH of the bird's nest acid-p-hydroxyacetophenone mixture to 3.5-7.

5.

3. The method according to any of claims 1-2, characterized in that, The mass percentage of the bird's nest acid is 0.01%-5%; and / or, the mass percentage of the p-hydroxyacetophenone is 0.01%-1%.

4. The method according to any one of claims 1 to 3, characterized in that, The mass percentage of the stabilizer is 0.01%-0.1%.

5. The method according to any one of claims 1 to 4, characterized in that, The sulfite includes one or more of sodium sulfite, potassium sulfite, ammonium sulfite, sodium metabisulfite or potassium metabisulfite.

6. The method according to any one of claims 1 to 5, characterized in that, The bisulfite includes one or more of sodium bisulfite, potassium bisulfite or ammonium bisulfite.

7. Use of the method of any one of claims 1-6 in the preparation of a cosmetic product containing bird's nest acid and p-hydroxyacetophenone.

8. Use of the method of any one of claims 1-7 in the improvement of the discoloration or loss of bird's nest acid of a bird's nest acid-p-hydroxyacetophenone solution.

9. A aqueous solution of a composition of a cubebin acid-p-hydroxyacetophenone, characterized in that, obtained by the method of any one of claims 1-6.

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